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1
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Saeed M, Shoaib A, Kandimalla R, Javed S, Almatroudi A, Gupta R, Aqil F. Microbe-based therapies for colorectal cancer: Advantages and limitations. Semin Cancer Biol 2022; 86:652-665. [PMID: 34020027 DOI: 10.1016/j.semcancer.2021.05.018] [Citation(s) in RCA: 31] [Impact Index Per Article: 10.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/14/2021] [Revised: 04/06/2021] [Accepted: 05/14/2021] [Indexed: 01/27/2023]
Abstract
Cancer is one of the leading global causes of death in both men and women. Colorectal cancer (CRC) alone accounts for ∼10 % of total new global cases and poses an over 4% lifetime risk of developing cancer. Recent advancements in the field of biotechnology and microbiology concocted novel microbe-based therapies to treat various cancers, including CRC. Microbes have been explored for human use since centuries, especially for the treatment of various ailments. The utility of microbes in cancer therapeutics is widely explored, and various bacteria, fungi, and viruses are currently in use for the development of cancer therapeutics. The human gut hosts about 100 trillion microbes that release their metabolites in active, inactive, or dead conditions. Microbial secondary metabolites, proteins, immunotoxins, and enzymes are used to target cancer cells to induce cell cycle arrest, apoptosis, and death. Various approaches, such as dietary interventions, the use of prebiotics and probiotics, and fecal microbiota transplantation have been used to modulate the gut microbiota in order to prevent or treat CRC pathogenesis. The present review highlights the role of the gut microbiota in CRC precipitation, the potential mechanisms and use of microorganisms as CRC biomarkers, and strategies to modulate microbiota for the prevention and treatment of CRC.
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Affiliation(s)
- Mohd Saeed
- Department of Biology, College of Sciences, University of Hail, Hail, Saudi Arabia
| | - Ambreen Shoaib
- Department of Clinical Pharmacy, College of Pharmacy, Jazan University, Jazan, Saudi Arabia
| | - Raghuram Kandimalla
- James Graham Brown Cancer Center, University of Louisville, Louisville, KY 40202, USA; Department of Pharmacology and Toxicology, University of Louisville, Louisville, KY 40202, USA
| | - Shamama Javed
- Department of Pharmaceutics, College of Pharmacy, Jazan University, Jazan, Saudi Arabia
| | - Ahmad Almatroudi
- Department of Medical Laboratories, College of Applied Medical Sciences, Qassim University, Qassim 51431, Saudi Arabia
| | - Ramesh Gupta
- James Graham Brown Cancer Center, University of Louisville, Louisville, KY 40202, USA; Department of Pharmacology and Toxicology, University of Louisville, Louisville, KY 40202, USA
| | - Farrukh Aqil
- James Graham Brown Cancer Center, University of Louisville, Louisville, KY 40202, USA; Department of Medicine, University of Louisville, Louisville, KY 40202, USA.
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2
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Abstract
The serrated pathway of carcinogenesis has been the subject of intense investigation over the past 2 decades, but many gaps in our understanding still need to be resolved. Serrated polyp precursors include hyperplastic polyps, sessile serrated polyps, and traditional serrated adenomas. These are considered discrete entities, but there is emerging molecular data to suggest that they may be more closely related to each other than currently believed. The recent US Multi-Society Task Force surveillance guidelines for patients with serrated polyps are admittedly based on low quality evidence. In this brief review, we discuss the limitations in endoscopic detection and pathologic interpretation of serrated polyps and the implications of these diagnostic difficulties on risk prediction and postpolypectomy surveillance recommendations.
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3
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Rubio CA, Schmidt PT. Asymmetric crypt fission in sessile serrated lesions. J Clin Pathol 2020; 74:712-717. [PMID: 33046564 DOI: 10.1136/jclinpath-2020-207008] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/05/2020] [Revised: 08/18/2020] [Accepted: 08/19/2020] [Indexed: 01/16/2023]
Abstract
OBJECTIVE Sessile serrated lesions without dysplasia (SSL-ND) are epitomised by dilated crypts with epithelial serrations and architectural distortions portraying boot-shapes, L-shapes or inverted-T shapes. Recently, crypts in asymmetric fission were detected in SSL-ND. The purpose was to assess the frequency of crypts in asymmetric fission in a cohort of SSL-ND. METHODS The frequency of crypts in fission was assessed in 60 SSL-ND, the distribution of cell proliferation in 48 SSL-ND and the expression of maspin, a tumour-suppressor protein, in 29 SSL-ND. RESULTS Out of the 60 SSL-ND, 40 (66.7%) showed crypts in fission: 39 (65%) SSL-ND had crypts in asymmetric fission and one SSL-ND (1.7%), in symmetric fission (p<0.05). Of 1495 crypts recorded in the 60 SSL-ND, 73 (4.9%) were in asymmetric fission but only one (0.06%), in symmetric fission (p<0.05). Out of the 48 Ki67-immunostained SSL-ND,15 (31%) showed randomly distributed proliferating cell-domains. All 29 SSL-ND revealed maspin-upregulation (including crypts in asymmetric and symmetric fission). In contrast, the normal colon mucosa showed occasional single crypts in symmetric fission, proliferating cell-domains limited to the lower thirds of the crypts, absence of crypts in asymmetric fission and remained maspin negative. CONCLUSIONS SSL-ND thrive with crypts in asymmetric fission displaying randomly distributed proliferating cell-domains and maspin-upregulation. These histo-biological aberrations disclose pathological cryptogenesis and suggest possibly unfolding somatic mutations in SSL-ND. The present findings may open new vistas on the parameters pertinent to the susceptibility of SSL-ND to develop dysplasia and carcinoma.
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Affiliation(s)
- Carlos A Rubio
- Department of Pathology, Karolinska Institute, Stockholm, Sweden
| | - Peter T Schmidt
- Medicine (Solna), Karolinska Institute and Ersta Hospital, Stockholm, Sweden
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4
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Sun BL. Current Microsatellite Instability Testing in Management of Colorectal Cancer. Clin Colorectal Cancer 2020; 20:e12-e20. [PMID: 32888812 DOI: 10.1016/j.clcc.2020.08.001] [Citation(s) in RCA: 38] [Impact Index Per Article: 7.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/09/2020] [Revised: 07/28/2020] [Accepted: 08/03/2020] [Indexed: 02/06/2023]
Abstract
Colorectal cancer (CRC) is the third most common cancer worldwide. In the past decade, mismatch repair deficiency (dMMR), manifested as microsatellite instability-high (MSI-H), has been recognized as a distinct mechanism promoting tumorigenesis in 15% of CRCs including 3% Lynch syndrome and 12% sporadic CRCs. As the molecular classifications of CRCs are continuously evolving, MSI-H CRCs appear to be the most homogeneous CRCs with distinct molecular, morphologic, and clinical features. MSI-H CRCs have dMMR causing MSI-H and genetic hypermutation but with diploid chromosomes. Morphologically, MSI-H CRCs appear as poorly differentiated or mucinous adenocarcinoma with characteristic lymphocytic infiltration. Most importantly, MSI-H CRCs have better stage-adjusted survival, do not respond well to standard 5-fluorouracil-based adjuvant chemotherapy, but do respond to immunotherapy. The United States Food and Drug Administration granted accelerated approval to immune checkpoint inhibitors, anti-programmed cell death protein-1 antibodies pembrolizumab and nivolumab, and the combination of nivolumab with anti-CTLA4 antibody ipilimumab for the second-line treatment of patients with stage IV MSI-H CRCs in 2017. There are still ongoing phase III clinical trials evaluating pembrolizumab and anti-programmed death-ligand 1 antibody atezolizumab as the first-line treatment in stage IV MSI-H CRCs and a phase I study on the combination of nivolumab and ipilimumab in patients with early stage CRC. These ongoing clinical studies on immunotherapy may lead to practice-changing results in the management of MSI-H CRCs. The National Comprehensive Cancer Network 2018 guidelines recommended MSI to be tested in all newly diagnosed CRCs. The MSI test will become increasingly vital in guiding adjuvant chemotherapy and immunotherapy in the management of CRCs.
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Affiliation(s)
- Belinda L Sun
- Department of Pathology, Banner-University Medical Center, University of Arizona, Tucson, AZ.
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Kowalczyk M, Orłowski M, Klepacki Ł, Zinkiewicz K, Kurpiewski W, Kaczerska D, Pesta W, Zieliński E, Siermontowski P. Rectal aberrant crypt foci (ACF) as a predictor of benign and malignant neoplastic lesions in the large intestine. BMC Cancer 2020; 20:133. [PMID: 32075595 PMCID: PMC7029492 DOI: 10.1186/s12885-020-6590-4] [Citation(s) in RCA: 13] [Impact Index Per Article: 2.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/23/2018] [Accepted: 01/30/2020] [Indexed: 12/29/2022] Open
Abstract
Background The importance of ACF is not fully explained, however, their number may be a good predictor of synchronous and metachronic adenoma or other polyps whose removal reduces the risk of CRC. Due to the epidemiological and genetic association of ACF with pre-cancer lesions, they may be a potential CRC biomarker. The aim of our study was to show that the number and type of rectal ACF may be a good predictive factor for the presence of polyps located proximally from the splenic flexure and that the type and number of ACF can correlate with the number and specific types of polyps in the large intestine. Methods The study included 131 patients who underwent colonoscopy combined with rectal mucosa staining with 0.25% methylene blue. The number of rectal ACF was determined and bioptats were sampled for histopathological examination to assess the type of ACF. Endoscopic ACF assessment criteria given by L. Roncucci were used. The obtained material was subjected to statistical analysis using probability distribution, U-test, t-student test, and chi 2 as well as the Statistica 7.1 software package. Results The study population was divided into three subgroups according to the number of ACF observed, i.e. ACF < 5, 5–10 and > 10. ACF < 5 were found in 35 patients (29.41%), 5–10 ACF in 70 (58.82%) and ACF > 10 in 14 individuals (11.76%). The study revealed the presence of normal ACF (p = 0.49), hyperplastic ACF (p = 0.34), dysplastic ACF (p = 0.11), and mixed ACF (p = 0.06). A single type of ACF was most commonly observed (n = 88, p = 0.74). In the researched group a larger number of ACF is concurrent with adenomas and hyperplastic polyps. The number of ACF clearly correlates with the dysplasia advancement in the adenoma and the number of polyps found. Conclusions Rectal ACF are a useful marker for the presence of cancerous lesions in the proximal and distal sections of the large intestine.
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Affiliation(s)
- Marek Kowalczyk
- Department of Oncologic and General Surgery, University Hospital in Olsztyn, Olsztyn, Poland.,Department of Laboratory Medicine, University Hospital in Olsztyn, Olsztyn, Poland
| | - Marcin Orłowski
- Centre for Diagnosis and Treatment of Gastrointestinal Diseases, Gdańsk, Poland
| | - Łukasz Klepacki
- Department of Anatomy, University Hospital in Olsztyn, Olsztyn, Poland.,Oncological and General Surgery Clinic, University Hospital in Olsztyn, Olsztyn, Poland
| | - Krzysztof Zinkiewicz
- 52nd Department of General, Gastroenterologic and Gastrointestinal Oncologic Surgery, Medical University of Lublin, University Hospital No.1, Lublin, Poland
| | - Waldemar Kurpiewski
- Department of Oncologic and General Surgery, University Hospital in Olsztyn, Olsztyn, Poland
| | | | - Wiesław Pesta
- Department of Oncologic and General Surgery, University Hospital in Olsztyn, Olsztyn, Poland
| | - Ewa Zieliński
- Department of Emergency Medicine and Disaster Collegium Medicum in Bydgoszcz, Nicolaus Copernicus University in Toruń, Toruń, Poland.
| | - Piotr Siermontowski
- Department of Underwater Works Technology, Polish Naval Academy, Gdynia, Poland.,Department of Maritime & Hyperbaric Medicine Department, Military Institute of Medicine Gdynia, Warsaw, Poland
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6
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Yozu M, Kem M, Cenaj O, Mino-Kenudson M, Odze RD, Misdraji J. Loss of expression of MLH1 in non-dysplastic crypts is a harbinger of neoplastic progression in sessile serrated adenomas/polyps. Histopathology 2019; 75:376-384. [PMID: 30974487 DOI: 10.1111/his.13874] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/05/2019] [Accepted: 04/08/2019] [Indexed: 01/26/2023]
Abstract
AIMS Dysplasia in colonic sessile serrated adenomas (SSAs)/sessile serrated polyps often shows loss of MLH1 expression as determined with immunohistochemistry, but the significance of loss of MLH1 expression in non-dysplastic crypts in these polyps is less well studied. The purpose of this study was to evaluate the prevalence of loss of MLH1 expression in non-dysplastic crypts in SSAs, and to evaluate its significance with regard to progression of these polyps. METHODS AND RESULTS Four hundred SSAs, including 158 SSAs without dysplasia, 219 SSAs with dysplasia (SSAD), and 23 SSAs with invasive adenocarcinoma (SSAC), were evaluated immunohistochemically for loss of MLH1 expression in both non-dysplastic and dysplastic portions of the polyps. Seventy-one of 400 (18%) SSAs showed loss of MLH1 expression in non-dysplastic crypts. The prevalence of MLH1-deficient non-dysplastic crypts was higher in polyps with dysplasia or carcinoma (7%, 22%, and 52% in SSAs, SSADs, and SSACs, respectively; P < 0.0001). When SSAs with MLH1-deficient dysplasia and those with MLH-1-proficient dysplasia were compared, those with MLH1-deficient dysplasia were more likely to have MLH1-deficient non-dysplastic crypts (66% versus 8.1%, P < 0.0001) and a greater number of discrete foci (3.6 foci versus 1.1 foci, P = 0.008). Also, non-dysplastic crypts with loss of MLH1 expression were more likely to be contiguous with the dysplasia when the dysplasia also showed loss of MLH1 expression (26% versus 0%, P = 0.02). CONCLUSIONS Our results suggest that loss of MLH1 expression in non-dysplastic crypts in SSAs precedes the development of MLH1-deficient dysplasia and adenocarcinoma, and may be a biomarker of an advanced serrated polyp even in the absence of dysplasia.
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Affiliation(s)
- Masato Yozu
- Histopathology Department, Middlemore Hospital, Auckland, New Zealand
| | - Marina Kem
- Department of Pathology, Massachusetts General Hospital and Harvard Medical School, Boston, MA, USA
| | - Odise Cenaj
- Department of Pathology, New York University Langone Medical Center and New York University School of Medicine, New York, NY, USA
| | - Mari Mino-Kenudson
- Department of Pathology, Massachusetts General Hospital and Harvard Medical School, Boston, MA, USA
| | - Robert D Odze
- Department of Pathology, Brigham and Women's Hospital and Harvard Medical School, Boston, MA, USA
| | - Joseph Misdraji
- Department of Pathology, Massachusetts General Hospital and Harvard Medical School, Boston, MA, USA
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7
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Leung JW, Yen AW, Jia H, Opada C, Melnik A, Atkins J, Feller C, Wilson MD, Leung FW. A prospective RCT comparing combined chromoendoscopy with water exchange (CWE) vs water exchange (WE) vs air insufflation (AI) in adenoma detection in screening colonoscopy. United European Gastroenterol J 2019; 7:477-487. [PMID: 31065365 DOI: 10.1177/2050640619832196] [Citation(s) in RCA: 11] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/16/2018] [Accepted: 01/22/2019] [Indexed: 12/15/2022] Open
Abstract
Background A low adenoma detection rate (ADR) increases risks of interval cancers (ICs). Proximal colon flat polyps, e.g. serrated lesions (SLs), are difficult to find. Missed proximal colon flat lesions likely contribute to IC. Aims We compared chromoendoscopy with water exchange (CWE), water exchange (WE) and air insufflation (AI) in detecting adenomas in screening colonoscopy. Methods After split-dose preparation, 480 veterans were randomized to AI, WE and CWE. Results Primary outcome of proximal ADR (55.6% vs 53.4% vs 52.2%, respectively) were similar in all groups. Adenoma per colonoscopy (APC) and adenoma per positive colonoscopy (APPC) were comparable. Detection rate of proximal colon SLs was significantly higher for CWE and WE than AI (26.3%, 23.6% and 11.3%, respectively, p = 0.002). Limitations: single operator; SLs only surrogate markers of but not IC. Conclusions When an endoscopist achieves high-quality AI examinations with overall ADR twice (61.6%) the recommended standard (30%), use of WE and CWE does not produce further improvement in proximal or overall ADR. Comparable APC and APPC confirm equivalent withdrawal inspection techniques. WE alone is sufficient to significantly improve detection of proximal SLs. The impact of increased detection of proximal SLs by WE on prevention of IC deserves to be studied. This study is registered at ClinicalTrial.gov (NCT#01607255).
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Affiliation(s)
- J W Leung
- Section of Gastroenterology, Sacramento Veteran Affairs Medical Center, Veteran Affairs Northern California Health Care System (VANCHCS), Mather, CA, USA.,Division of Gastroenterology and Hepatology, University of California, Davis School of Medicine, Sacramento, CA, USA
| | - A W Yen
- Section of Gastroenterology, Sacramento Veteran Affairs Medical Center, Veteran Affairs Northern California Health Care System (VANCHCS), Mather, CA, USA
| | - H Jia
- Department of Gastroenterology, Xijing Hospital of Digestive Diseases, Fourth Military Medical University, Xi'an, Shaanxi, China
| | - C Opada
- Section of Gastroenterology, Sacramento Veteran Affairs Medical Center, Veteran Affairs Northern California Health Care System (VANCHCS), Mather, CA, USA
| | - A Melnik
- Section of Gastroenterology, Sacramento Veteran Affairs Medical Center, Veteran Affairs Northern California Health Care System (VANCHCS), Mather, CA, USA
| | - J Atkins
- Section of Gastroenterology, Sacramento Veteran Affairs Medical Center, Veteran Affairs Northern California Health Care System (VANCHCS), Mather, CA, USA
| | - C Feller
- Section of Gastroenterology, Sacramento Veteran Affairs Medical Center, Veteran Affairs Northern California Health Care System (VANCHCS), Mather, CA, USA
| | - M D Wilson
- Clinical and Translational Science Center, Department of Public Health Sciences, Division of Biostatistics, University of California, Davis, Sacramento, CA, USA
| | - F W Leung
- Sepulveda Ambulatory Care Center, Veteran Affairs Greater Los Angeles Healthcare System (VAGLAHS) and David Geffen School of Medicine at UCLA, North Hills, CA, USA
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8
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Bläker H, Alwers E, Arnold A, Herpel E, Tagscherer KE, Roth W, Jansen L, Walter V, Kloor M, Chang-Claude J, Brenner H, Hoffmeister M. The Association Between Mutations in BRAF and Colorectal Cancer-Specific Survival Depends on Microsatellite Status and Tumor Stage. Clin Gastroenterol Hepatol 2019; 17:455-462.e6. [PMID: 29660527 DOI: 10.1016/j.cgh.2018.04.015] [Citation(s) in RCA: 56] [Impact Index Per Article: 9.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/22/2017] [Revised: 03/29/2018] [Accepted: 04/08/2018] [Indexed: 02/07/2023]
Abstract
BACKGROUND & AIMS Colorectal tumors with mutations in BRAF and microsatellite stability (MSS) have been associated with adverse outcomes of patients. Combined tests for microsatellite instability-high (MSI-H) and BRAF mutations might therefore be used in risk assessment, particularly for patients with stage II tumors. We investigate the stage-specific prognostic value of combined testing for MSI-H and BRAF for patients with colorectal cancer. METHODS We performed a retrospective analysis of colorectal tumor samples collected from 1995 patients at 22 hospitals in Germany, between 2003 and 2010. Samples were analyzed for MSI-H using an established mononucleotide marker panel; BRAF mutations (BRAFV600E) were detected by Sanger sequencing or in tissue microarray blocks using immunohistochemistry. Cancers were assigned to categories of having MSS without mutations in BRAF, MSS with mutant BRAF, MSI-H without mutations in BRAF, and MSI-H with mutant BRAF. We investigated the association between tumor categories with clinical and pathologic features and patient's overall, disease-specific, and recurrence-free survival (median follow-up time, 5.1 y). RESULTS Tumors were stage I in 364 (18%), stage II in 678 (34%), stage III in 673 (34%), and stage IV (14%) in 280 patients. Sixty-three percent of tumors were located in the colon and 37% in the rectum. Most tumors (85%) had MSS without mutations in BRAF, 3% had MSS with mutant BRAF, 7% had MSI-H without mutations in BRAF, and 5% had MSI-H with mutant BRAF. In patients whose tumors were MSI-H, mutation of BRAF did not significantly affect survival time. Patients whose tumors had MSS with mutant BRAF had significantly reduced overall survival (hazard ratio [HR], 2.16; 95% CI, 1.54-3.04; P < .001), disease-specific survival (HR, 2.59; 95% CI, 1.77-3.79; P < .001), and recurrence-free survival (HR, 2.45; 95% CI, 1.70-3.52; P < .001) than patients whose tumors had MSS without BRAF mutation. Although BRAF mutations in tumors with MSS were associated with disease-specific survival of patients with stage III or IV tumors (P < .001), these features did not affect survival of patients with stage II tumors (P = .639). CONCLUSIONS In an analysis of almost 2000 patients with colorectal cancer, we found BRAF mutations to reduce survival of patients in stage III or IV (but not stage II) tumors with MSS. These findings do not support testing stage I or II colorectal tumors for BRAF mutations, although additional large studies are needed.
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Affiliation(s)
- Hendrik Bläker
- Department of General Pathology, Institute of Pathology, Charité University Medicine Hospital, Berlin, Germany.
| | - Elizabeth Alwers
- Division of Clinical Epidemiology and Aging Research, German Cancer Research Center (DKFZ), Heidelberg, Germany
| | - Alexander Arnold
- Department of General Pathology, Institute of Pathology, Charité University Medicine Hospital, Berlin, Germany
| | - Esther Herpel
- Institute of Pathology, University Hospital Heidelberg, Heidelberg, Germany; Tissue Bank, National Center for Tumor Diseases, Heidelberg, Germany
| | - Katrin E Tagscherer
- Institute of Pathology, University Hospital Heidelberg, Heidelberg, Germany; Institute of Pathology, University Medical Center Mainz, Mainz, Germany
| | - Wilfried Roth
- Institute of Pathology, University Hospital Heidelberg, Heidelberg, Germany; Institute of Pathology, University Medical Center Mainz, Mainz, Germany
| | - Lina Jansen
- Division of Clinical Epidemiology and Aging Research, German Cancer Research Center (DKFZ), Heidelberg, Germany
| | - Viola Walter
- Division of Clinical Epidemiology and Aging Research, German Cancer Research Center (DKFZ), Heidelberg, Germany
| | - Matthias Kloor
- Department of Applied Tumor Biology, Institute of Pathology, University of Heidelberg, Heidelberg, Germany
| | - Jenny Chang-Claude
- Division of Cancer Epidemiology, German Cancer Research Center (DKFZ), Heidelberg, Germany; Genetic Tumor Epidemiology Group, University Medical Center Hamburg-Eppendorf, Hamburg, Germany
| | - Hermann Brenner
- Division of Clinical Epidemiology and Aging Research, German Cancer Research Center (DKFZ), Heidelberg, Germany; Tissue Bank, National Center for Tumor Diseases, Heidelberg, Germany; Division of Preventive Oncology, German Cancer Research Center (DKFZ), Heidelberg, Germany; German Cancer Consortium (Deutschen Konsortium für Translationale Krebsforschung), German Cancer Research Center (Deutsches Krebsforschungszentrum), Heidelberg, Germany
| | - Michael Hoffmeister
- Division of Clinical Epidemiology and Aging Research, German Cancer Research Center (DKFZ), Heidelberg, Germany
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9
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Abbass MA, Kalady MF. Serrated polyposis syndrome: Diagnosis and management. SEMINARS IN COLON AND RECTAL SURGERY 2018. [DOI: 10.1053/j.scrs.2018.06.008] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/11/2022]
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Abstract
Our understanding of the genetics of colorectal cancer has changed dramatically over recent years. Colorectal cancer can be classified in multiple different ways. Along with the advent of whole-exome sequencing, we have gained an understanding of the scale of the genetic changes found in sporadic colorectal cancer. We now know that there are multiple pathways that are commonly involved in the evolution of colorectal cancer including Wnt/β-catenin, RAS, EGFR, and PIK3 kinase. Another recent leap in our understanding of colorectal cancer genetics is the recognition that many, if not all tumors, are actually genetically heterogeneous within individual tumors and also between tumors. Recent research has revealed the prognostic and possibly therapeutic implications of various specific mutations, including specific mutations in BRAF and KRAS . There is increasing interest in the use of mutation testing for screening and surveillance through stool and circulating DNA testing. Recent advances in translational research in colorectal cancer genetics are dramatically changing our understanding of colorectal cancer and will likely change therapy and surveillance in the near future.
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Affiliation(s)
- Karin M Hardiman
- Division of Colon and Rectal Surgery, Department of Surgery, University of Michigan, Ann Arbor, Michigan
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11
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Zorcolo L, Fantola G, Balestrino L, Restivo A, Vivanet C, Spina F, Cabras F, Ambu R, Casula G. MUTYH-associated colon disease: Adenomatous polyposis is only one of the possible phenotypes. A family report and literature review. TUMORI JOURNAL 2018; 97:676-80. [DOI: 10.1177/030089161109700523] [Citation(s) in RCA: 6] [Impact Index Per Article: 0.9] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/04/2023]
Abstract
Aims and background The MutY human homologue gene (MUTYH) is responsible for about a quarter of attenuated familial adenomatous polyposis. Occasionally, it has been associated with hyperplastic polyps and serrated adenoma. We report a family where the same MUTYH mutation determined four different phenotypes, including a case of hyperplastic polyposis syndrome. Patients and methods A family with a history of right-sided colon cancer and multiple colonic polyposis was investigated. Genetic tests were correlated with clinical findings to define phenotypic manifestations of MUTYH mutations. The pertinent English-language literature was reviewed to evaluate the risk of malignancy of MUTYH and the role of prophylactic surgery. Results Three male siblings carried a biallelic MUTYH mutation (G382D-exon13), while the fourth was heterozygote. One developed an isolated cecal cancer at the age of 48. Another, aged 38, was diagnosed with numerous minute colonic and rectal polyps and underwent a proctocolectomy, with final pathology showing a picture of hyperplastic and lymphoid polyposis. The third biallelic brother, 46 years old, developed four hyperplastic lesions, while the heterozygote brother had a large flat serrated adenoma of the right colon removed at the age of 50. Conclusion Many aspects of MUTYH mutation still need to be clarified and one of them regards the different phenotypic expressions. Although the majority of reported cases manifested attenuated adenomatous polyposis, hyperplastic polyps and serrated adenomas appear to be more common than expected. Presenting hyperplastic polyposis syndrome is very unusual and may represent a clinical dilemma for correct management. Current evidence suggests to handle MUTYH-associated polyposis as typical FAP.
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Affiliation(s)
- Luigi Zorcolo
- Department of General Surgery, Colorectal Unit, University of Cagliari, Cagliari
| | - Giovanni Fantola
- Department of General Surgery, Colorectal Unit, University of Cagliari, Cagliari
| | | | - Angelo Restivo
- Department of General Surgery, Colorectal Unit, University of Cagliari, Cagliari
| | | | | | - Francesco Cabras
- Department of General Surgery, Colorectal Unit, University of Cagliari, Cagliari
| | - Rossano Ambu
- Department of Pathology, University of Cagliari, Cagliari, Italy
| | - Giuseppe Casula
- Department of General Surgery, Colorectal Unit, University of Cagliari, Cagliari
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12
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Kim DH, Lubner MG, Cahoon AR, Pooler BD, Pickhardt PJ. Flat Serrated Polyps at CT Colonography: Relevance, Appearance, and Optimizing Interpretation. Radiographics 2017; 38:60-74. [PMID: 29148927 DOI: 10.1148/rg.2018170110] [Citation(s) in RCA: 24] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/17/2023]
Abstract
Serrated polyps are a recently recognized family of colonic polyps with subgroups that harbor future malignant potential. In the past, the significance of these lesions to the colorectal cancer carcinogenesis pathway was not recognized nor well understood. It is now known that serrated polyps account for approximately one-fourth of all sporadic colorectal cancers. The sessile serrated polyp (SSP) (also known as a sessile serrated adenoma [SSA]) is the main lesion of interest given its prevalence and subtle presentation. These lesions are often flat-only minimally raised from the colonic surface-and occur in the right colon. These lesions have been a likely common cause of screening failure at colonoscopy, although detection has improved with improved recognition over time. Although detection is difficult with image-based screening, serrated lesions can be detected at CT colonography. The prevalence in CT colonography screening populations mirrors the rates at colonoscopy for similar size categories. CT colonography allows identification of SSPs despite their minimally raised profile owing to the phenomenon of lesional contrast material coating. This contrast material coat aids in lesion detection by highlighting the subtle morphologic changes as well as increasing confidence that a true lesion exists despite a flat morphology. It is important to optimize contrast material coating with specific bowel preparations and other technical parameters. Radiologists should be aware of these technical and interpretation issues. Armed with this knowledge, radiologists should expect excellent results in detection of these subtle but important lesions. ©RSNA, 2017.
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Affiliation(s)
- David H Kim
- From the Department of Radiology, University of Wisconsin School of Medicine and Public Health, E3/311 Clinical Science Center, 600 Highland Ave, Madison, WI 53792-3252
| | - Meghan G Lubner
- From the Department of Radiology, University of Wisconsin School of Medicine and Public Health, E3/311 Clinical Science Center, 600 Highland Ave, Madison, WI 53792-3252
| | - Ashley R Cahoon
- From the Department of Radiology, University of Wisconsin School of Medicine and Public Health, E3/311 Clinical Science Center, 600 Highland Ave, Madison, WI 53792-3252
| | - B Dustin Pooler
- From the Department of Radiology, University of Wisconsin School of Medicine and Public Health, E3/311 Clinical Science Center, 600 Highland Ave, Madison, WI 53792-3252
| | - Perry J Pickhardt
- From the Department of Radiology, University of Wisconsin School of Medicine and Public Health, E3/311 Clinical Science Center, 600 Highland Ave, Madison, WI 53792-3252
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Rhee YY, Kim KJ, Kang GH. CpG Island Methylator Phenotype-High Colorectal Cancers and Their Prognostic Implications and Relationships with the Serrated Neoplasia Pathway. Gut Liver 2017; 11:38-46. [PMID: 27885175 PMCID: PMC5221859 DOI: 10.5009/gnl15535] [Citation(s) in RCA: 28] [Impact Index Per Article: 3.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/23/2015] [Accepted: 03/29/2016] [Indexed: 12/20/2022] Open
Abstract
The concept of a CpG island methylator phenotype (CIMP) was first introduced by Toyota and Issa to describe a subset of colorectal cancers (CRCs) with concurrent hypermethylation of multiple CpG island loci. The concept of CIMP as a molecular carcinogenesis mechanism was consolidated by the identification of the serrated neoplasia pathway, in which CIMP participates in the initiation and progression of serrated adenomas. Distinct clinicopathological and molecular features of CIMP-high (CIMP-H) CRCs have been characterized, including proximal colon location, older age of onset, female preponderance, and frequent associations of high-level microsatellite instability and BRAF mutations. CIMP-H CRCs arise in sessile or traditional serrated adenomas and thus tend to display the morphological characteristics of serrated adenomas, including epithelial serration, vesicular nuclei, and abundant cytoplasm. Both the frequent association of CIMP and poor prognosis and different responses of CRCs to adjuvant therapy depending on CIMP status indicate clinical implications. In this review, we present an overview of the literature documenting the relevant findings of CIMP-H CRCs and their relationships with the serrated neoplasia pathway.
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Affiliation(s)
- Ye-Young Rhee
- Department of Pathology, Seoul National University College of Medicine, Seoul, Korea
| | - Kyung-Ju Kim
- Department of Pathology, Seoul National University College of Medicine, Seoul, Korea
| | - Gyeong Hoon Kang
- Department of Pathology, Seoul National University College of Medicine, Seoul, Korea
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Hattori T, Sentani K, Naohide O, Sakamoto N, Yasui W. Clinicopathological significance of SPC18 in colorectal cancer: SPC18 participates in tumor progression. Cancer Sci 2017; 108:143-150. [PMID: 27859949 PMCID: PMC5276824 DOI: 10.1111/cas.13121] [Citation(s) in RCA: 15] [Impact Index Per Article: 1.9] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/18/2016] [Revised: 10/27/2016] [Accepted: 11/11/2016] [Indexed: 12/25/2022] Open
Abstract
Colorectal cancer (CRC) is one of the leading causes of cancer‐related death worldwide. In order to identify novel prognostic markers or therapeutic targets for CRC, we searched for candidate genes in our comprehensive gene expression libraries, and focused on SEC11A, which encodes the SPC18 protein. SPC18 plays a key role in the endoplasmic reticulum‐Golgi secretory pathway and presumably regulates the secretion of various secretory proteins. An immunohistochemical analysis of SPC18 in 137 CRC tissue samples demonstrated that 79 (58%) CRC cases were positive for SPC18. SPC18‐positive CRC cases were more advanced in terms of N classification (P = 0.0315) and tumor stage (P = 0.0240) than SPC18‐negative CRC cases. Furthermore, the expression of SPC18 was an independent prognostic classifier for CRC patients. The cell growth and invasiveness of SPC18 siRNA‐transfected CRC cell lines was less than that of the negative control siRNA‐transfected cell lines. The levels of phosphorylated epidermal growth factor receptor, Erk and Akt were lower in SPC18 siRNA‐transfected CRC cells than in control cells. The expression of SPC18 was colocalized with β‐catenin nuclear localization and MMP7 at the invasive front. An immunohistochemical analysis of human colorectal polyp specimens revealed a sequential increase in the expression of SPC18 through the conventional adenoma‐carcinoma pathway, while SPC18 was not expressed or was expressed to a lesser extent in serrated pathway‐related tumors. These results suggest that SPC18 is involved in tumor progression, and is an independent prognostic classifier in patients with CRC.
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Affiliation(s)
- Takuya Hattori
- Department of Molecular Pathology, Hiroshima University Institute of Biomedical and Health Sciences, Hiroshima, Japan
| | - Kazuhiro Sentani
- Department of Molecular Pathology, Hiroshima University Institute of Biomedical and Health Sciences, Hiroshima, Japan
| | - Oue Naohide
- Department of Molecular Pathology, Hiroshima University Institute of Biomedical and Health Sciences, Hiroshima, Japan
| | - Naoya Sakamoto
- Department of Molecular Pathology, Hiroshima University Institute of Biomedical and Health Sciences, Hiroshima, Japan
| | - Wataru Yasui
- Department of Molecular Pathology, Hiroshima University Institute of Biomedical and Health Sciences, Hiroshima, Japan
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15
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Carballal S, Rodríguez-Alcalde D, Moreira L, Hernández L, Rodríguez L, Rodríguez-Moranta F, Gonzalo V, Bujanda L, Bessa X, Poves C, Cubiella J, Castro I, González M, Moya E, Oquiñena S, Clofent J, Quintero E, Esteban P, Piñol V, Fernández FJ, Jover R, Cid L, López-Cerón M, Cuatrecasas M, López-Vicente J, Leoz ML, Rivero-Sánchez L, Castells A, Pellisé M, Balaguer F. Colorectal cancer risk factors in patients with serrated polyposis syndrome: a large multicentre study. Gut 2016; 65:1829-1837. [PMID: 26264224 DOI: 10.1136/gutjnl-2015-309647] [Citation(s) in RCA: 63] [Impact Index Per Article: 7.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/23/2015] [Revised: 07/08/2015] [Accepted: 07/10/2015] [Indexed: 12/16/2022]
Abstract
OBJECTIVE Serrated polyposis syndrome (SPS) is associated with an increased colorectal cancer (CRC) risk, although the magnitude of the risk remains uncertain. Whereas intensive endoscopic surveillance for CRC prevention is advised, predictors that identify patients who have high CRC risk remain unknown. We performed a multicentre nationwide study aimed at describing the CRC risk in patients with SPS and identifying clinicopathological predictors independently associated with CRC. DESIGN From March 2013 through September 2014, patients with SPS were retrospectively recruited at 18 Spanish centres. Data were collected from medical, endoscopy and histopathology reports. Multivariate logistic regression was performed to identify CRC risk factors. RESULTS In 296 patients with SPS with a median follow-up time of 45 months (IQR 26-79.7), a median of 26 (IQR 18.2-40.7) serrated polyps and 3 (IQR 1-6) adenomas per patient were detected. Forty-seven patients (15.8%) developed CRC at a mean age of 53.9±12.8, and 4 out of 47 (8.5%) tumours were detected during surveillance (cumulative CRC incidence 1.9%). Patients with >2 sessile serrated adenomas/polyps (SSA/Ps) proximal to splenic flexure and ≥1 proximal SSA/P with high-grade dysplasia were independent CRC risk factors (incremental OR=2, 95% CI 1.22 to 3.24, p=0.006). Patients with no risk factors showed a 55% decrease in CRC risk (OR=0.45, 95% CI 0.24 to 0.86, p=0.01). CONCLUSIONS Patients with SPS have an increased risk of CRC, although lower than previously published. Close colonoscopy surveillance in experienced centres show a low risk of developing CRC (1.9% in 5 years). Specific polyp features (SSA/P histology, proximal location and presence of high-grade dysplasia) should be used to guide clinical management.
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Affiliation(s)
- Sabela Carballal
- Gastroenterology Department, Hospital Clínic de Barcelona, Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas (CIBERehd), Institut d'Investigacions Biomediques August Pi i Sunyer (IDIBAPS), Universitat de Barcelona, Barcelona, Spain
| | | | - Leticia Moreira
- Gastroenterology Department, Hospital Clínic de Barcelona, Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas (CIBERehd), Institut d'Investigacions Biomediques August Pi i Sunyer (IDIBAPS), Universitat de Barcelona, Barcelona, Spain
| | - Luis Hernández
- Digestive Disease Section, Hospital Universitario de Móstoles, Madrid, Spain
| | - Lorena Rodríguez
- Gastroenterology Department, Hospital Universitario de Bellvitge, Hospitalet de Llobregat, Barcelona, Spain
| | | | - Victoria Gonzalo
- Gastroenterology Department, Hospital Universitari Mútua de Terrassa, Terrassa, Barcelona, Spain
| | - Luis Bujanda
- Gastroenterology Department, Hospital Donostia/Instituto Biodonostia, Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas (CIBERehd), Universidad del País Vasco (UPV/EHU), San Sebastián, Spain
| | - Xavier Bessa
- Gastroenterology Department, Hospital del Mar, Barcelona, Spain
| | - Carmen Poves
- Gastroenterology Department, Hospital Clínico de San Carlos, Madrid, Spain
| | - Joaquin Cubiella
- Gastroenterology Department, Complexo Hospitalario Universitario de Ourense, Instituto de Investigación Biomédica Ourense, Pontevedra y Vigo, Ourense, Spain
| | - Inés Castro
- Gastroenterology Department, Complexo Hospitalario Universitario de Ourense, Instituto de Investigación Biomédica Ourense, Pontevedra y Vigo, Ourense, Spain
| | - Mariano González
- Gastroenterology Department, Hospital Puerta del Hierro, Madrid, Spain
| | - Eloísa Moya
- Gastroenterology Department, Hospital Universitario del Sureste, Arganda del Rey, Madrid, Spain
| | - Susana Oquiñena
- Gastroenterology Department, Complejo Hospitalario de Navarra, Navarra, Spain
| | - Joan Clofent
- Gastroenterology Department, Hospital de Sagunto, Sagunto, Valencia, Spain
| | - Enrique Quintero
- Gastroenterology Department, Hospital Universitario de Canarias, Tenerife, Spain
| | - Pilar Esteban
- Gastroenterology Department, Hospital Morales Meseguer, Murcia, Spain
| | - Virginia Piñol
- Gastroenterology Department, Hospital Josep Trueta, Girona, Spain
| | | | - Rodrigo Jover
- Gastroenterology Department, Hospital General de Alicante, Alicante, Spain
| | - Lucía Cid
- Gastroenterology Department, Complexo Hospitalario Universitario de Vigo, Instituto de Investigación Biomedica Ourense, Pontevedra, y Vigo, Vigo, Spain
| | - María López-Cerón
- Gastroenterology Department, Hospital Clínic de Barcelona, Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas (CIBERehd), Institut d'Investigacions Biomediques August Pi i Sunyer (IDIBAPS), Universitat de Barcelona, Barcelona, Spain
| | - Miriam Cuatrecasas
- Pathology Department, Centre for Biomedical Diagnosis, Hospital Clínic de Barcelona, Barcelona, Spain
| | - Jorge López-Vicente
- Digestive Disease Section, Hospital Universitario de Móstoles, Madrid, Spain
| | - Maria Liz Leoz
- Gastroenterology Department, Hospital Clínic de Barcelona, Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas (CIBERehd), Institut d'Investigacions Biomediques August Pi i Sunyer (IDIBAPS), Universitat de Barcelona, Barcelona, Spain
| | - Liseth Rivero-Sánchez
- Gastroenterology Department, Hospital Clínic de Barcelona, Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas (CIBERehd), Institut d'Investigacions Biomediques August Pi i Sunyer (IDIBAPS), Universitat de Barcelona, Barcelona, Spain
| | - Antoni Castells
- Gastroenterology Department, Hospital Clínic de Barcelona, Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas (CIBERehd), Institut d'Investigacions Biomediques August Pi i Sunyer (IDIBAPS), Universitat de Barcelona, Barcelona, Spain
| | - María Pellisé
- Gastroenterology Department, Hospital Clínic de Barcelona, Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas (CIBERehd), Institut d'Investigacions Biomediques August Pi i Sunyer (IDIBAPS), Universitat de Barcelona, Barcelona, Spain
| | - Francesc Balaguer
- Gastroenterology Department, Hospital Clínic de Barcelona, Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas (CIBERehd), Institut d'Investigacions Biomediques August Pi i Sunyer (IDIBAPS), Universitat de Barcelona, Barcelona, Spain
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16
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Silva P, Albuquerque C, Lage P, Fontes V, Fonseca R, Vitoriano I, Filipe B, Rodrigues P, Moita S, Ferreira S, Sousa R, Claro I, Nobre Leitão C, Chaves P, Dias Pereira A. Serrated polyposis associated with a family history of colorectal cancer and/or polyps: The preferential location of polyps in the colon and rectum defines two molecular entities. Int J Mol Med 2016; 38:687-702. [PMID: 27430658 PMCID: PMC4990292 DOI: 10.3892/ijmm.2016.2666] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/13/2015] [Accepted: 03/11/2016] [Indexed: 12/25/2022] Open
Abstract
Serrated polyposis (SPP) is characterized by the development of multiple serrated polyps and an increased predisposition to colorectal cancer (CRC). In the present study, we aimed to characterize, at a clinical and molecular level, a cohort of SPP patients with or without a family history of SPP and/or polyps/CRC (SPP-FHP/CRC). Sixty-two lesions from 12 patients with SPP-FHP/CRC and 6 patients with sporadic SPP were included. The patients with SPP-FHP/CRC presented with an older mean age at diagnosis (p=0.027) and a more heterogeneous histological pattern of lesions (p=0.032) than the patients with sporadic SPP. We identified two molecular forms of SPP-FHP/CRC, according to the preferential location of the lesions: proximal/whole-colon or distal colon. Mismatch repair (MMR) gene methylation [mutS homolog 6 (MSH6)/mutS homolog 3 (MSH3)] or loss of heterozygosity (LOH) of D2S123 (flanking MSH6) were detected exclusively in the former (p=3.0×10−7), in most early lesions. Proximal/whole-colon SPP-FHP/CRC presented a higher frequency of O-6-methylguanine-DNA methyltransferase (MGMT) methylation/LOH, microsatel-lite instability (MSI) and Wnt mutations (19/29 vs. 7/17; 16/23 vs. 1/14, p=2.2×10−4; 15/26 vs. 2/15, p=0.006; 14/26 vs. 4/20, p=0.02) but a lower frequency of B-raf proto-oncogene, serine/threonine kinase (BRAF) mutations (7/30 vs. 12/20, p=0.0089) than the distal form. CRC was more frequent in cases of Kirsten rat sarcoma viral oncogene homolog (KRAS)-associated proximal/whole-colon SPP-FHP/CRC than in the remaining cases (4/4 vs. 1/8, p=0.01). Thus, SPP-FHP/CRC appears to be a specific entity, presenting two forms, proximal/whole-colon and distal, which differ in the underlying tumor initiation pathways. Early MGMT and MMR gene deficiency in the former may underlie an inherited susceptibility to genotoxic stress.
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Affiliation(s)
- Patrícia Silva
- Molecular Pathobiology Research Unit (UIPM), Portuguese Institute of Oncology of Lisbon Francisco Gentil, E.P.E. (IPOLFG, EPE), Lisbon, Portugal
| | - Cristina Albuquerque
- Molecular Pathobiology Research Unit (UIPM), Portuguese Institute of Oncology of Lisbon Francisco Gentil, E.P.E. (IPOLFG, EPE), Lisbon, Portugal
| | - Pedro Lage
- Gastroenterology Service, Portuguese Institute of Oncology of Lisbon Francisco Gentil, E.P.E. (IPOLFG, EPE), Lisbon, Portugal
| | - Vanessa Fontes
- Molecular Pathobiology Research Unit (UIPM), Portuguese Institute of Oncology of Lisbon Francisco Gentil, E.P.E. (IPOLFG, EPE), Lisbon, Portugal
| | - Ricardo Fonseca
- Pathology Service, Portuguese Institute of Oncology of Lisbon Francisco Gentil, E.P.E. (IPOLFG, EPE), Lisbon, Portugal
| | - Inês Vitoriano
- Molecular Pathobiology Research Unit (UIPM), Portuguese Institute of Oncology of Lisbon Francisco Gentil, E.P.E. (IPOLFG, EPE), Lisbon, Portugal
| | - Bruno Filipe
- Molecular Pathobiology Research Unit (UIPM), Portuguese Institute of Oncology of Lisbon Francisco Gentil, E.P.E. (IPOLFG, EPE), Lisbon, Portugal
| | - Paula Rodrigues
- Familial Cancer Risk Clinic, Portuguese Institute of Oncology of Lisbon Francisco Gentil, E.P.E. (IPOLFG, EPE), Lisbon, Portugal
| | - Susana Moita
- Molecular Pathobiology Research Unit (UIPM), Portuguese Institute of Oncology of Lisbon Francisco Gentil, E.P.E. (IPOLFG, EPE), Lisbon, Portugal
| | - Sara Ferreira
- Gastroenterology Service, Portuguese Institute of Oncology of Lisbon Francisco Gentil, E.P.E. (IPOLFG, EPE), Lisbon, Portugal
| | - Rita Sousa
- Gastroenterology Service, Portuguese Institute of Oncology of Lisbon Francisco Gentil, E.P.E. (IPOLFG, EPE), Lisbon, Portugal
| | - Isabel Claro
- Gastroenterology Service, Portuguese Institute of Oncology of Lisbon Francisco Gentil, E.P.E. (IPOLFG, EPE), Lisbon, Portugal
| | - Carlos Nobre Leitão
- Gastroenterology Service, Portuguese Institute of Oncology of Lisbon Francisco Gentil, E.P.E. (IPOLFG, EPE), Lisbon, Portugal
| | - Paula Chaves
- Pathology Service, Portuguese Institute of Oncology of Lisbon Francisco Gentil, E.P.E. (IPOLFG, EPE), Lisbon, Portugal
| | - António Dias Pereira
- Gastroenterology Service, Portuguese Institute of Oncology of Lisbon Francisco Gentil, E.P.E. (IPOLFG, EPE), Lisbon, Portugal
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He EY, Wyld L, Sloane MA, Canfell K, Ward RL. The molecular characteristics of colonic neoplasms in serrated polyposis: a systematic review and meta-analysis. JOURNAL OF PATHOLOGY CLINICAL RESEARCH 2016; 2:127-37. [PMID: 27499922 PMCID: PMC4958734 DOI: 10.1002/cjp2.44] [Citation(s) in RCA: 11] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 11/26/2015] [Accepted: 03/17/2016] [Indexed: 01/08/2023]
Abstract
Serrated polyposis is a rare disorder characterised by the presence of multiple serrated polyps in the large intestine, and an increased personal and familial risk of colorectal cancer. Knowledge of the molecular characteristics of colonic lesions which develop in this syndrome is fragmented, making it difficult to understand the underlying genetic basis of this condition. We conducted a systematic review and meta-analysis of all studies which evaluated the molecular characteristics of colorectal neoplasms found in individuals with serrated polyposis. We identified 4561 potentially relevant studies, but due to a lack of consensus in the reporting of findings, only fourteen studies were able to be included in the meta-analysis. BRAF mutation was found in 73% (95% CI 65-80%) of serrated polyps, 0% (95% CI 0-3%) of conventional adenomas and 49% (95%CI 33-64%) of colorectal cancers. In contrast, KRAS mutation was present in 8% (95% CI 5-11%) of serrated polyps, 3% (95% CI 0-13%) of conventional adenomas and 6% (95% CI 0-13%) of colorectal cancers. Absence of MLH1 immunostaining was found in 3% (95% CI 0-10%) of serrated polyps and 53% (95% CI 36-71%) of colorectal cancers. Overall, microsatellite instability was found in 40% (95% CI 18-64%) of colorectal cancers arising in the setting of serrated polyposis. Our results indicate that diverse molecular pathways are likely to contribute to the increased predisposition for colorectal cancer in individuals with serrated polyposis. We also propose a set of minimum standards for the reporting of future research in serrated polyposis as this is a rare syndrome and collation of research findings from different centres will be essential to identify the molecular mechanisms involved in the pathogenesis of this condition.
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Affiliation(s)
- Emily Y He
- Prince of Wales Clinical School, University of New South Wales Sydney, Australia
| | - Lucy Wyld
- Prince of Wales Clinical School, University of New South Wales Sydney, Australia
| | - Mathew A Sloane
- Prince of Wales Clinical School, University of New South Wales Sydney, Australia
| | - Karen Canfell
- Prince of Wales Clinical School, University of New South WalesSydney, Australia; Cancer Council NSWSydney, Australia
| | - Robyn L Ward
- Prince of Wales Clinical School, University of New South WalesSydney, Australia; Office of the Deputy Vice-Chancellor (Research), University of QueenslandBrisbane, Australia
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18
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Sameer AS, Nissar S. Understanding Epigenetics: an Alternative Mechanism of Colorectal Carcinogenesis. CURRENT COLORECTAL CANCER REPORTS 2016. [DOI: 10.1007/s11888-016-0317-6] [Citation(s) in RCA: 6] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/31/2022]
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Epigenetics in diagnosis of colorectal cancer. MOLECULAR BIOLOGY RESEARCH COMMUNICATIONS 2016; 5:49-57. [PMID: 27844020 PMCID: PMC5019333] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Download PDF] [Subscribe] [Scholar Register] [Indexed: 12/02/2022]
Abstract
Colorectal cancer (CRC) is a third most common epithelial carcinoma. CRC is known to develop from the early precancerous lesion to full blown malignancy via definite phases due to cumulative mutations and aberrant methylation of number of genes. The use of serum biomarkers that is non-invasive to discriminate cancer patients from healthy persons will prove to be an important tool to improve the early diagnosis of CRC. This will serve as the boon to the clinical management of the disease.
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20
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Bejarano PA, Garcia-Buitrago MT, Berho M, Allende D. Biologic and molecular markers for staging colon carcinoma. COLORECTAL CANCER 2016. [DOI: 10.2217/crc.15.27] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/07/2023]
Abstract
Biomarkers in the field of pathology and oncology may allow for the detection of disease, assessment of prognosis or to predict response to certain therapy. Molecular abnormalities in colorectal cancer genesis may occur due to chromosome instability, microsatellite instability and DNA methylation (CpG island methylator phenotype). These alterations are associated in some cases to sporadic carcinomas whereas in others are seen in syndrome-related tumors and are the basis for the use of different biomarkers in the clinical setting. These may include mismatched repair gene/proteins, RAS, BRAF, PIK3CA, which help to determine tumor prognosis and predict response to certain drugs.
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Affiliation(s)
- Pablo A Bejarano
- Department of Pathology Cleveland Clinic Florida, 2900 Weston Road, Weston, FL 33331, USA
| | - Monica T Garcia-Buitrago
- Department of Pathology, University of Miami School of Medicine, 1611 NW 12 Ave. Holtz Bldg, Miami, FL 33136, USA
| | - Mariana Berho
- Department of Pathology Cleveland Clinic Florida, 2900 Weston Road, Weston, FL 33331, USA
| | - Daniela Allende
- Department of Pathology Cleveland Clinic, Cleveland, OH 9500 Euclid Avenue Cleveland, OH 44195, USA
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21
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Szylberg Ł, Janiczek M, Popiel A, Marszałek A. Expression of COX-2, IL-1β, TNF-α and IL-4 in epithelium of serrated adenoma, adenoma and hyperplastic polyp. Arch Med Sci 2016; 12:172-8. [PMID: 26925134 PMCID: PMC4754379 DOI: 10.5114/aoms.2016.57594] [Citation(s) in RCA: 13] [Impact Index Per Article: 1.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/28/2013] [Accepted: 02/22/2014] [Indexed: 12/26/2022] Open
Abstract
INTRODUCTION Colon polyps and inflammatory process play the key role in neoplasia of colorectal cancer. In recent years there have been many publications on the malignancy of hyperplastic polyp (HP) which according to the WHO classification is a non-neoplastic polyp. The aim of this study is to determine the expression of inflammatory proteins COX-2, IL-1β, TNF-α and IL-4 in the epithelium of colorectal polyps. MATERIAL AND METHODS In the study, 144 colorectal polyps were analyzed. The groups of HP, classical (A) and serrated adenomas (SA) and normal mucosa (control) according to histopathological studies were selected. Immunohistochemical examinations Rusing antibodies against COX-2, IL-1β, TNF-α and IL-4 were performed. The expression of analyzed protein was evaluated using modified Remmele-Stegner scale (0-16). RESULTS Statistical analysis revealed higher expression of TNF-α (16 ±3.87 vs. 1 ±5.06), IL-1β (12 ±4 vs 8 ±2.72), COX-2 (9 ±2.54 vs. 8 ±3.14) and IL-4 (12 ±3.45 vs. 4 ±3.35) in SA polyps compared to the control (p < 0.001). The HP had an increased level of expression of TNF-α (12 ±3.72 vs. 1 ±5.06, p < 0.005), COX-2 (8.5 ±1.97 vs. 8 ±3.14, p < 0.012) and IL-4 (12 ±3.46 vs. 4 ±3.35, p < 0.001). Significantly higher expression of IL-4 (12 ±2.32 vs. 4 ±3.35, p < 0.001) and IL-1β (16 ±4.32 vs. 8 ±2.72, p < 0.044) in A compared to the control were observed. CONCLUSIONS Expression of inflammatory factors differed between polyps. Inflammation accompanied the serrated structures which occur in polyps. The inflammatory process affects the development of colorectal polyps. The HP may predispose to malignancy.
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Affiliation(s)
- Łukasz Szylberg
- Department of Clinical Pathomorphology, Collegium Medicum in Bydgoszcz, Nicolaus Copernicus University in Torun, Poland
| | - Marlena Janiczek
- Department of Clinical Pathomorphology, Collegium Medicum in Bydgoszcz, Nicolaus Copernicus University in Torun, Poland
| | - Aneta Popiel
- Department of Clinical Pathomorphology, Collegium Medicum in Bydgoszcz, Nicolaus Copernicus University in Torun, Poland
| | - Andrzej Marszałek
- Department of Clinical Pathomorphology, Collegium Medicum in Bydgoszcz, Nicolaus Copernicus University in Torun, Poland
- Department of Tumor Pathology and Prophylaxis, Poznan University of Medical Sciences and Greater Poland Cancer Center, Poznan, Poland
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Abstract
Colorectal cancer (CRC) is considered a heterogeneous disease, both regarding pathogenesis and clinical behaviour. Four decades ago, the adenoma-carcinoma pathway was presented as the main pathway towards CRC, a conclusion that was largely based on evidence from observational morphological studies. This concept was later substantiated at the genomic level. Over the past decade, evidence has been generated for alternative routes in which CRC might develop, in particular the serrated neoplasia pathway. Providing indisputable evidence for the neoplastic potential of serrated polyps has been difficult. Reasons include the absence of reliable longitudinal observations on individual serrated lesions that progress to cancer, a shortage of available animal models for serrated lesions and challenging culture conditions when generating organoids of serrated lesions for in vitro studies. However, a growing body of circumstantial evidence has been accumulated, which indicates that ≥15% of CRCs might arise through the serrated neoplasia pathway. An even larger amount of post-colonoscopy colorectal carcinomas (carcinomas occurring within the surveillance interval after a complete colonoscopy) have been suggested to originate from serrated polyps. The aim of this Review is to assess the current status of the serrated neoplasia pathway in CRC and highlight clinical implications.
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23
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East JE, Vieth M, Rex DK. Serrated lesions in colorectal cancer screening: detection, resection, pathology and surveillance. Gut 2015; 64:991-1000. [PMID: 25748647 DOI: 10.1136/gutjnl-2014-309041] [Citation(s) in RCA: 89] [Impact Index Per Article: 8.9] [Reference Citation Analysis] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/16/2014] [Accepted: 02/12/2015] [Indexed: 12/13/2022]
Affiliation(s)
- James E East
- Translational Gastroenterology Unit, University of Oxford, Oxford, UK
| | - Michael Vieth
- Institute of Pathology, Klinikum Bayreuth, Bayreuth, Germany
| | - Douglas K Rex
- Indiana University School of Medicine, Indianapolis, Indiana, USA
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Serrated polyps and their alternative pathway to the colorectal cancer: a systematic review. Gastroenterol Res Pract 2015; 2015:573814. [PMID: 25945086 PMCID: PMC4405010 DOI: 10.1155/2015/573814] [Citation(s) in RCA: 34] [Impact Index Per Article: 3.4] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/25/2014] [Revised: 03/20/2015] [Accepted: 03/22/2015] [Indexed: 12/15/2022] Open
Abstract
Colorectal cancer (CRC) is the third most frequently diagnosed cancer in the world. For a long time, only one pathway of colorectal carcinogenesis was known. In recent years, a new “alternative” pathway through serrated adenoma was described. Recent meta-analysis estimated these cancers as about 10% to 30% of all CRCs. Serrated polyps are the second most popular groups of polyps (after conventional adenomas) found during colonoscopy. Serrated polyps of the colon are clinically and molecularly diverse changes that have common feature as crypt luminal morphology characterized by glandular serration. Evidence suggests that subtypes of serrated polyps, particularly TSA and SSA/P, can lead to adenocarcinoma through the serrated pathway. Moreover, the data indicate that the SSA/P are the precursors of colorectal carcinoma by MSI and may be subject to rapid progression to malignancy. An important step to reduce the incidence of CRC initiated by the serrated pathway is to improve the detection of serrated polyps and to ensure their complete removal during endoscopy. Understanding of the so-called serrated carcinogenesis pathway is an important step forward in expanding possibilities in the prevention of CRC.
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Narrow-band imaging for the detection of polyps in patients with serrated polyposis syndrome: a multicenter, randomized, back-to-back trial. Gastrointest Endosc 2015; 81:531-8. [PMID: 25088921 DOI: 10.1016/j.gie.2014.06.043] [Citation(s) in RCA: 29] [Impact Index Per Article: 2.9] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/18/2014] [Accepted: 06/26/2014] [Indexed: 02/08/2023]
Abstract
BACKGROUND Serrated polyposis syndrome (SPS) is characterized by the presence of multiple serrated polyps spread throughout the colon. Patients with SPS are considered to be at risk of colorectal cancer and are advised to undergo endoscopic surveillance. Narrow-band imaging (NBI) may improve the detection of polyps during these surveillance colonoscopies. OBJECTIVE To compare polyp miss rates between NBI and high-resolution white-light endoscopy (HR-WLE). DESIGN Multicenter, randomized, crossover study. SETTING Four tertiary referral institutions. PATIENTS A total of 52 patients with SPS undergoing surveillance colonoscopy. INTERVENTION All patients underwent back-to-back colonoscopies with HR-WLE and NBI in a randomized order. MAIN OUTCOME MEASUREMENTS Polyp miss rates of HR-WLE and NBI. RESULTS In the HR-WLE group, 116 polyps were detected during the first inspection. A second inspection with NBI added 47 polyps, resulting in an overall polyp miss rate of 29% with HR-WLE (95% confidence interval, 22-36). In the NBI group, a total of 128 polyps were detected during the first inspection. Subsequent inspection with HR-WLE added 32 polyps, resulting in an overall polyp miss rate of NBI of 20% (95% confidence interval, 15-27). Comparison of the overall polyp miss rates of HR-WLE and NBI showed no significant difference (P = .065). LIMITATIONS Small sample size; second inspection was performed by the same endoscopist. CONCLUSIONS The results of our study suggest that NBI does not reduce polyp miss rates in patients with SPS compared with HR-WLE. Further multinational studies with larger numbers of patients are warranted to verify these results. ( CLINICAL TRIAL REGISTRATION NUMBER NTR2497.).
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Bordaçahar B, Barret M, Terris B, Dhooge M, Dreanic J, Prat F, Coriat R, Chaussade S. Sessile serrated adenoma: from identification to resection. Dig Liver Dis 2015; 47:95-102. [PMID: 25445408 DOI: 10.1016/j.dld.2014.09.006] [Citation(s) in RCA: 34] [Impact Index Per Article: 3.4] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/26/2014] [Accepted: 09/13/2014] [Indexed: 02/07/2023]
Abstract
Until the past two decades, almost all colorectal polyps were divided into two main groups: hyperplastic polyps and adenomas. Sessile serrated adenomas presented endoscopic, pathological and molecular profiles distinct from others polyps. Previously under-diagnosed, physicians now identified sessile serrated adenomas. The serrated neoplastic pathway is accounting for up to one-third of all sporadic colorectal cancers and sessile serrated adenomas have been identified as the main precursor lesions in serrated carcinogenesis. By analogy with the adenoma-adenocarcinoma sequence, the sessile serrated adenomas-adenocarcinoma sequence, has been identified. The development of endoscopic resection techniques permits the consideration of a non-surgical approach as the first option regardless of the size of the lesion. Sessile serrated adenoma warrants the watchfulness of physicians and requires an optimal quality of the colonoscopy procedure, a thorough evaluation of the lesion, an adequate endoscopic resection and follow-up colonoscopies in accordance with sessile serrated adenomas guidelines. We herein present a review on sessile serrated adenomas focusing on their pathological specificities, epidemiology, treatment modalities and follow-up.
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Affiliation(s)
- Benoît Bordaçahar
- Department of Gastroenterology, Cochin Teaching Hospital, AP-HP, Paris, France
| | - Maximilien Barret
- Department of Gastroenterology, Cochin Teaching Hospital, AP-HP, Paris, France; Paris Descartes University, Sorbonne Paris Cité, Paris, France
| | - Benoît Terris
- Paris Descartes University, Sorbonne Paris Cité, Paris, France; Department of Pathology, Cochin Teaching Hospital, AP-HP, Paris, France
| | - Marion Dhooge
- Department of Gastroenterology, Cochin Teaching Hospital, AP-HP, Paris, France; Paris Descartes University, Sorbonne Paris Cité, Paris, France
| | - Johann Dreanic
- Department of Gastroenterology, Cochin Teaching Hospital, AP-HP, Paris, France; Paris Descartes University, Sorbonne Paris Cité, Paris, France
| | - Frédéric Prat
- Department of Gastroenterology, Cochin Teaching Hospital, AP-HP, Paris, France; Paris Descartes University, Sorbonne Paris Cité, Paris, France
| | - Romain Coriat
- Department of Gastroenterology, Cochin Teaching Hospital, AP-HP, Paris, France; Paris Descartes University, Sorbonne Paris Cité, Paris, France.
| | - Stanislas Chaussade
- Department of Gastroenterology, Cochin Teaching Hospital, AP-HP, Paris, France; Paris Descartes University, Sorbonne Paris Cité, Paris, France
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Schlussel AT, Gagliano RA, Seto-Donlon S, Eggerding F, Donlon T, Berenberg J, Lynch HT. The evolution of colorectal cancer genetics-Part 1: from discovery to practice. J Gastrointest Oncol 2014; 5:326-35. [PMID: 25276405 DOI: 10.3978/j.issn.2078-6891.2014.069] [Citation(s) in RCA: 9] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/03/2014] [Accepted: 07/22/2014] [Indexed: 01/26/2023] Open
Abstract
Colorectal cancer (CRC) is an increasing burden on our society. Identifying those who are at the greatest risk and improving triage for treatment will have the greatest impact on healthcare. CRC is a prime paradigm for cancer genetics: the majority of disease results from stages of progression lending itself to prevention by early detection of the pre-disease (neoplastic) state. Approximately 10% represent well defined hereditary cancer syndromes. Hereditary CRC has the added benefit that many are slow growing and family members are armed with the knowledge of potential risk of associated carcinomas and empowerment to reduce the disease burden. This knowledge provides the indication for early endoscopic and/or surgical intervention for prevention or treatment of an entire family cohort. The molecular basis of CRC allows enhanced characterization of carcinomas, leading to targeted therapies.
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Affiliation(s)
- Andrew T Schlussel
- 1 Department of Surgery, Tripler Army Medical Center, Honolulu, HI, USA ; 2 The University of Arizona Cancer Center @ Dignity Health-St. Joseph's Hospital and Medical Center, Phoenix, AZ, USA ; 3 Genetics Laboratory, Huntington Medical Research Institutes, Pasadena, CA, USA ; 4 Ohana Genetics, Inc., Honolulu, HI, USA ; 5 Department of Cell & Molecular Biology, John A. Burns School of Medicine, University of Hawaii, Honolulu, HI, USA ; 6 Department of Oncology, Tripler Army Medical Center, Honolulu, HI, USA ; 7 Hereditary Cancer Institute, Department of Preventative Medicine, Creighton University School of Medicine, Omaha, NE, USA
| | - Ronald A Gagliano
- 1 Department of Surgery, Tripler Army Medical Center, Honolulu, HI, USA ; 2 The University of Arizona Cancer Center @ Dignity Health-St. Joseph's Hospital and Medical Center, Phoenix, AZ, USA ; 3 Genetics Laboratory, Huntington Medical Research Institutes, Pasadena, CA, USA ; 4 Ohana Genetics, Inc., Honolulu, HI, USA ; 5 Department of Cell & Molecular Biology, John A. Burns School of Medicine, University of Hawaii, Honolulu, HI, USA ; 6 Department of Oncology, Tripler Army Medical Center, Honolulu, HI, USA ; 7 Hereditary Cancer Institute, Department of Preventative Medicine, Creighton University School of Medicine, Omaha, NE, USA
| | - Susan Seto-Donlon
- 1 Department of Surgery, Tripler Army Medical Center, Honolulu, HI, USA ; 2 The University of Arizona Cancer Center @ Dignity Health-St. Joseph's Hospital and Medical Center, Phoenix, AZ, USA ; 3 Genetics Laboratory, Huntington Medical Research Institutes, Pasadena, CA, USA ; 4 Ohana Genetics, Inc., Honolulu, HI, USA ; 5 Department of Cell & Molecular Biology, John A. Burns School of Medicine, University of Hawaii, Honolulu, HI, USA ; 6 Department of Oncology, Tripler Army Medical Center, Honolulu, HI, USA ; 7 Hereditary Cancer Institute, Department of Preventative Medicine, Creighton University School of Medicine, Omaha, NE, USA
| | - Faye Eggerding
- 1 Department of Surgery, Tripler Army Medical Center, Honolulu, HI, USA ; 2 The University of Arizona Cancer Center @ Dignity Health-St. Joseph's Hospital and Medical Center, Phoenix, AZ, USA ; 3 Genetics Laboratory, Huntington Medical Research Institutes, Pasadena, CA, USA ; 4 Ohana Genetics, Inc., Honolulu, HI, USA ; 5 Department of Cell & Molecular Biology, John A. Burns School of Medicine, University of Hawaii, Honolulu, HI, USA ; 6 Department of Oncology, Tripler Army Medical Center, Honolulu, HI, USA ; 7 Hereditary Cancer Institute, Department of Preventative Medicine, Creighton University School of Medicine, Omaha, NE, USA
| | - Timothy Donlon
- 1 Department of Surgery, Tripler Army Medical Center, Honolulu, HI, USA ; 2 The University of Arizona Cancer Center @ Dignity Health-St. Joseph's Hospital and Medical Center, Phoenix, AZ, USA ; 3 Genetics Laboratory, Huntington Medical Research Institutes, Pasadena, CA, USA ; 4 Ohana Genetics, Inc., Honolulu, HI, USA ; 5 Department of Cell & Molecular Biology, John A. Burns School of Medicine, University of Hawaii, Honolulu, HI, USA ; 6 Department of Oncology, Tripler Army Medical Center, Honolulu, HI, USA ; 7 Hereditary Cancer Institute, Department of Preventative Medicine, Creighton University School of Medicine, Omaha, NE, USA
| | - Jeffrey Berenberg
- 1 Department of Surgery, Tripler Army Medical Center, Honolulu, HI, USA ; 2 The University of Arizona Cancer Center @ Dignity Health-St. Joseph's Hospital and Medical Center, Phoenix, AZ, USA ; 3 Genetics Laboratory, Huntington Medical Research Institutes, Pasadena, CA, USA ; 4 Ohana Genetics, Inc., Honolulu, HI, USA ; 5 Department of Cell & Molecular Biology, John A. Burns School of Medicine, University of Hawaii, Honolulu, HI, USA ; 6 Department of Oncology, Tripler Army Medical Center, Honolulu, HI, USA ; 7 Hereditary Cancer Institute, Department of Preventative Medicine, Creighton University School of Medicine, Omaha, NE, USA
| | - Henry T Lynch
- 1 Department of Surgery, Tripler Army Medical Center, Honolulu, HI, USA ; 2 The University of Arizona Cancer Center @ Dignity Health-St. Joseph's Hospital and Medical Center, Phoenix, AZ, USA ; 3 Genetics Laboratory, Huntington Medical Research Institutes, Pasadena, CA, USA ; 4 Ohana Genetics, Inc., Honolulu, HI, USA ; 5 Department of Cell & Molecular Biology, John A. Burns School of Medicine, University of Hawaii, Honolulu, HI, USA ; 6 Department of Oncology, Tripler Army Medical Center, Honolulu, HI, USA ; 7 Hereditary Cancer Institute, Department of Preventative Medicine, Creighton University School of Medicine, Omaha, NE, USA
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Siraj AK, Bu R, Prabhakaran S, Bavi P, Beg S, Al Hazmi M, Al-Rasheed M, Alobaisi K, Al-Dayel F, AlManea H, Al-Sanea N, Uddin S, Al-Kuraya KS. A very low incidence of BRAF mutations in Middle Eastern colorectal carcinoma. Mol Cancer 2014; 13:168. [PMID: 25005754 PMCID: PMC4109832 DOI: 10.1186/1476-4598-13-168] [Citation(s) in RCA: 29] [Impact Index Per Article: 2.6] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/27/2014] [Accepted: 06/24/2014] [Indexed: 02/08/2023] Open
Abstract
BACKGROUND Recent studies emphasize the role of BRAF as a genetic marker for prediction, prognosis and risk stratification in colorectal cancer. Earlier studies have reported the incidence of BRAF mutations in the range of 5-20% in colorectal carcinomas (CRC) and are predominantly seen in the serrated adenoma-carcinoma pathway characterized by microsatellite instability (MSI-H) and hypermethylation of the MLH1 gene in the setting of the CpG island methylator phenotype (CIMP). Due to the lack of data on the true incidence of BRAF mutations in Saudi Arabia, we sought to analyze the incidence of BRAF mutations in this ethnic group. METHODS 770 CRC cases were analyzed for BRAF and KRAS mutations by direct DNA sequencing. RESULTS BRAF gene mutations were seen in 2.5% (19/757) CRC analyzed and BRAF V600E somatic mutation constituted 90% (17/19) of all BRAF mutations. BRAF mutations were significantly associated with right sided tumors (p = 0.0019), MSI-H status (p = 0.0144), CIMP (p = 0.0017) and a high proliferative index of Ki67 expression (p = 0.0162). Incidence of KRAS mutations was 28.6% (216/755) and a mutual exclusivity was noted with BRAF mutations (p = 0.0518; a trend was seen). CONCLUSION Our results highlight the low incidence of BRAF mutations and CIMP in CRC from Saudi Arabia. This could be attributed to ethnic differences and warrant further investigation to elucidate the effect of other environmental and genetic factors. These findings indirectly suggest the possibility of a higher incidence of familial hereditary colorectal cancers especially Hereditary non polyposis colorectal cancer (HNPCC) syndrome /Lynch Syndrome (LS) in Saudi Arabia.
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Affiliation(s)
- Abdul K Siraj
- Human Cancer Genomic Research, Research Center, King Faisal Specialist Hospital and Research Center, MBC#98-16, P.O. Box 3354 Riyadh 11211, Saudi Arabia
| | - Rong Bu
- Human Cancer Genomic Research, Research Center, King Faisal Specialist Hospital and Research Center, MBC#98-16, P.O. Box 3354 Riyadh 11211, Saudi Arabia
| | - Sarita Prabhakaran
- Human Cancer Genomic Research, Research Center, King Faisal Specialist Hospital and Research Center, MBC#98-16, P.O. Box 3354 Riyadh 11211, Saudi Arabia
| | - Prashant Bavi
- Human Cancer Genomic Research, Research Center, King Faisal Specialist Hospital and Research Center, MBC#98-16, P.O. Box 3354 Riyadh 11211, Saudi Arabia
| | - Shaham Beg
- Human Cancer Genomic Research, Research Center, King Faisal Specialist Hospital and Research Center, MBC#98-16, P.O. Box 3354 Riyadh 11211, Saudi Arabia
| | - Mohsen Al Hazmi
- Human Cancer Genomic Research, Research Center, King Faisal Specialist Hospital and Research Center, MBC#98-16, P.O. Box 3354 Riyadh 11211, Saudi Arabia
| | - Maha Al-Rasheed
- Human Cancer Genomic Research, Research Center, King Faisal Specialist Hospital and Research Center, MBC#98-16, P.O. Box 3354 Riyadh 11211, Saudi Arabia
| | - Khadija Alobaisi
- Human Cancer Genomic Research, Research Center, King Faisal Specialist Hospital and Research Center, MBC#98-16, P.O. Box 3354 Riyadh 11211, Saudi Arabia
| | - Fouad Al-Dayel
- Department of Pathology, King Faisal Specialist Hospital and Research Center, Riyadh, Saudi Arabia
| | - Hadeel AlManea
- Department of Pathology, King Faisal Specialist Hospital and Research Center, Riyadh, Saudi Arabia
| | - Nasser Al-Sanea
- Colorectal Unit, Department of Surgery, King Faisal Specialist Hospital and Research Center, Riyadh, Saudi Arabia
| | - Shahab Uddin
- Human Cancer Genomic Research, Research Center, King Faisal Specialist Hospital and Research Center, MBC#98-16, P.O. Box 3354 Riyadh 11211, Saudi Arabia
| | - Khawla S Al-Kuraya
- Human Cancer Genomic Research, Research Center, King Faisal Specialist Hospital and Research Center, MBC#98-16, P.O. Box 3354 Riyadh 11211, Saudi Arabia
- Department of Pathology, College of Medicine, Alfaisal University, Riyadh, Saudi Arabia
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Hazewinkel Y, Tytgat KMAJ, van Eeden S, Bastiaansen B, Tanis PJ, Boparai KS, Fockens P, Dekker E. Incidence of colonic neoplasia in patients with serrated polyposis syndrome who undergo annual endoscopic surveillance. Gastroenterology 2014; 147:88-95. [PMID: 24657624 DOI: 10.1053/j.gastro.2014.03.015] [Citation(s) in RCA: 40] [Impact Index Per Article: 3.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/04/2013] [Revised: 03/09/2014] [Accepted: 03/14/2014] [Indexed: 02/07/2023]
Abstract
BACKGROUND & AIMS Patients with serrated polyposis syndrome (SPS) are advised to undergo endoscopic surveillance for early detection of polyps and prevention of colorectal cancer (CRC). The optimal surveillance and treatment regimen is unknown. We performed a prospective study to evaluate a standardized endoscopic treatment protocol in a large cohort of patients with SPS. METHODS We followed a cohort of patients with SPS who received annual endoscopic surveillance at the Academic Medical Centre in Amsterdam, The Netherlands from January 2007 through December 2012. All patients underwent clearing colonoscopy with removal of all polyps ≥3 mm. After clearance, subsequent follow-up colonoscopies were scheduled annually. The primary outcomes measure was the incidence of CRC and polyps. Secondary outcomes were the incidence of complications and the rate of preventive surgery. RESULTS Successful endoscopic clearance of all polyps ≥3 mm was achieved in 41 of 50 (82%) patients. During subsequent annual surveillance, with a median follow-up time of 3.1 years (interquartile range, 1.5-4.3 years), CRC was not detected. The cumulative risks of detecting CRC, advanced adenomas, or large (≥10 mm) serrated polyps after 3 surveillance colonoscopies were 0%, 9%, 34%, respectively. Twelve patients (24%) were referred for preventive surgery; 9 at initial colonoscopy and 3 during surveillance. Perforations or severe bleeding did not occur. CONCLUSIONS Annual surveillance with complete removal of all polyps ≥3 mm with timely referral of selected high-risk patients for prophylactic surgery prevents development of CRC in SPS patients without significant morbidity. Considering the substantial risk of polyp recurrence, close endoscopic surveillance in SPS seems warranted. www.trialregister.nl ID NTR2757.
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Affiliation(s)
- Yark Hazewinkel
- Department of Gastroenterology and Hepatology, Academic Medical Center, Amsterdam, The Netherlands
| | - Kristien M A J Tytgat
- Department of Gastroenterology and Hepatology, Academic Medical Center, Amsterdam, The Netherlands
| | - Susanne van Eeden
- Department of Pathology, Academic Medical Center, Amsterdam, The Netherlands
| | - Barbara Bastiaansen
- Department of Gastroenterology and Hepatology, Academic Medical Center, Amsterdam, The Netherlands
| | - Pieter J Tanis
- Department of Surgery, Academic Medical Center, Amsterdam, The Netherlands
| | - Karam S Boparai
- Department of Gastroenterology and Hepatology, Academic Medical Center, Amsterdam, The Netherlands
| | - Paul Fockens
- Department of Gastroenterology and Hepatology, Academic Medical Center, Amsterdam, The Netherlands
| | - Evelien Dekker
- Department of Gastroenterology and Hepatology, Academic Medical Center, Amsterdam, The Netherlands.
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Payne SR, Church TR, Wandell M, Rösch T, Osborn N, Snover D, Day RW, Ransohoff DF, Rex DK. Endoscopic detection of proximal serrated lesions and pathologic identification of sessile serrated adenomas/polyps vary on the basis of center. Clin Gastroenterol Hepatol 2014; 12:1119-26. [PMID: 24333512 DOI: 10.1016/j.cgh.2013.11.034] [Citation(s) in RCA: 120] [Impact Index Per Article: 10.9] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/03/2013] [Revised: 11/05/2013] [Accepted: 11/12/2013] [Indexed: 02/07/2023]
Abstract
BACKGROUND & AIMS We investigated rates of detection of proximal serrated lesions in a cohort of average-risk patients undergoing screening colonoscopies. METHODS We reviewed results from screening colonoscopies performed by attending gastroenterologists at 32 endoscopy centers from 2008-2010. Pathology slides were interpreted at the individual centers. For this analysis, serrated lesions included hyperplastic polyps larger than 10 mm, those interpreted as sessile serrated adenomas (or sessile serrated polyp), and traditional serrated adenomas. Rates of detection for conventional adenomas and serrated lesions were compared among centers. RESULTS A total of 5778 lesions were detected in 7215 screening colonoscopies. Of the 5548 lesions with pathology results, 3008 (54.2%) were conventional adenomas, 350 (6.3%) were serrated, and 232 (4.2%) were proximal serrated. The proportion of colonoscopies with at least 1 proximal serrated lesion was 2.8% (range among centers, 0%-9.8%). The number of serrated lesions per colonoscopy ranged from 0.00-0.11 (average, 0.05 ± 0.25). Overall lesion detection rates correlated with proximal serrated lesion detection rates (R = 0.91, P < .0001); conventional adenoma and proximal serrated lesion detection rates also correlated (R = .43, P = .025). The detection rate of proximal serrated lesions differed significantly among centers (P < .0001); odds ratios for detection ranged from 0-0.79. Some centers' pathologists never identified proximal serrated lesions as sessile serrated adenomas/polyps. CONCLUSIONS In an average-risk screening cohort, detection of proximal serrated lesions varied greatly among endoscopy centers. There was also substantial variation among pathologists in identification of sessile serrated adenomas/polyps. Nationally, a significant proportion of proximal serrated lesions may be missed during colonoscopy examination or incorrectly identified during pathology assessment. ClinicalTrials.gov Number: NCT00855348.
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Affiliation(s)
| | - Timothy R Church
- University of Minnesota School of Public Health, Minneapolis, Minnesota
| | | | - Thomas Rösch
- Department of Interdisciplinary Endoscopy, University Hospital Hamburg-Eppendorf, Hamburg, Germany
| | - Neal Osborn
- Atlanta Gastroenterology Associates, Atlanta, Georgia
| | - Dale Snover
- Fairview Southdale Hospital, Minneapolis, Minnesota
| | - Robert W Day
- Fred Hutchinson Cancer Research Center, Seattle, Washington; Epigenomics, Inc, Seattle, Washington
| | - David F Ransohoff
- Departments of Medicine and Epidemiology, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina
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Claudin-1 Expression Is Elevated in Colorectal Cancer Precursor Lesions Harboring the BRAF V600E Mutation. Transl Oncol 2014; 7:456-63. [PMID: 24954356 PMCID: PMC4202803 DOI: 10.1016/j.tranon.2014.05.009] [Citation(s) in RCA: 17] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/18/2014] [Revised: 05/15/2014] [Accepted: 05/21/2014] [Indexed: 12/26/2022] Open
Abstract
BACKGROUND: Sessile serrated adenomas/polyps (SSA/P) are now recognised precursors of colorectal cancer (CRC) including cancers harbouring somatic BRAF (V600E) mutations. While the morphological diagnostic criteria of SSA/P have been established, distinguishing between small/early SSA/P and microvesicular hyperplastic polyps (MVHP) is challenging and may not be possible in routine practice. METHODS: Gene expression profiling of MVHP (n=5, all BRAF V600E wild-type) and SSA/P (n=5, all BRAF V600E mutant) samples was performed. Quantitative reverse transcription–polymerase chain reaction (qRT-PCR) and immunohistochemical analysis was performed to verify the expression of claudin 1 (CLDN1) in MVHP and SSA/P. RESULTS: Gene expression profiling studies conducted between MVHP and SSA/P identified CLDN1 as the most statistically significant differentially expressed gene (p<0.05). Validation with qRT-PCR confirmed an up-regulation of CLDN1 in BRAF V600E mutant polyps regardless of polyp type (p<0.0005). Immunohistochemical analysis of CLDN1 expression in BRAF V600E mutant SSA/Ps (n=53) and MVHPs (n=111) and BRAF wild-type MVHPs (n=58), demonstrated a strong correlation between CLDN1 expression and the BRAF V600E mutation in both SSA/P and MVHP samples when compared to wild-type polyps (p<0.0001). CONCLUSION: This study demonstrates an up regulation of CLDN1 protein in serrated colorectal polyps including MVHP harbouring the BRAF V600E mutation. Our results demonstrated an apparent heterogeneity on the molecular level within the MVHP group and suggest that MVHP with somatic BRAF V600E mutation and up-regulated expression of CLDN1 are closely related to SSA/P and may in fact represent a continuous spectrum of the same neoplastic process within the serrated pathway of colorectal carcinogenesis.
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La Nauze R, Suzuki N, Saunders B, Clark S, Thomas-Gibson S. The endoscopist's guide to serrated polyposis. Colorectal Dis 2014; 16:417-25. [PMID: 24702773 DOI: 10.1111/codi.12475] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/05/2013] [Accepted: 10/10/2013] [Indexed: 01/14/2023]
Abstract
AIM Serrated polyposis is a condition of the colon characterized by multiple serrated polyps. This review aims to provide a practical guide to the day-to-day management of serrated polyposis, including diagnosis, endoscopic identification of serrated polyps, surveillance, the role of endoscopic and surgical management and the screening of family members. METHOD The literature was searched using PubMed and MEDLINE databases for the terms "serrated polyp", "serrated polyposis" and "hyperplastic polyposis". English-language abstracts were read and the full article was retrieved if relevant to the review. Expert opinion from the authors was also sought. RESULTS Advances in our knowledge of the molecular pathways involved in serrated polyposis and an improved clinical picture of the disease from retrospective studies have led to better understanding of its pathogenesis and natural history. However, there are still areas not answered by the literature, and hence empirical management or expert opinion has to be followed. CONCLUSION Improvements in our understanding of serrated polyposis, together with improvements in endoscopic equipment and technique, have enabled the endoscopist to be at the forefront of managing this condition from diagnosis to endoscopic surveillance and control of the polyps.
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Affiliation(s)
- R La Nauze
- The Wolfson Unit for Endoscopy, St Mark's Hospital, Harrow, London, UK; Department of Gastroenterology, Alfred Hospital, Melbourne, Victoria, Australia
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VE1 immunohistochemistry accurately detects BRAF V600E mutations in colorectal carcinoma and can be utilized in the detection of poorly differentiated colorectal serrated adenocarcinoma. Virchows Arch 2014; 464:637-43. [DOI: 10.1007/s00428-014-1555-0] [Citation(s) in RCA: 19] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/16/2013] [Revised: 01/22/2014] [Accepted: 02/09/2014] [Indexed: 12/28/2022]
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Delker DA, McGettigan BM, Kanth P, Pop S, Neklason DW, Bronner MP, Burt RW, Hagedorn CH. RNA sequencing of sessile serrated colon polyps identifies differentially expressed genes and immunohistochemical markers. PLoS One 2014; 9:e88367. [PMID: 24533081 PMCID: PMC3922809 DOI: 10.1371/journal.pone.0088367] [Citation(s) in RCA: 52] [Impact Index Per Article: 4.7] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/26/2013] [Accepted: 01/06/2014] [Indexed: 02/06/2023] Open
Abstract
BACKGROUND Sessile serrated adenomas/polyps (SSA/Ps) may account for 20-30% of colon cancers. Although large SSA/Ps are generally recognized phenotypically, small (<1 cm) or dysplastic SSA/Ps are difficult to differentiate from hyperplastic or small adenomatous polyps by endoscopy and histopathology. Our aim was to define the comprehensive gene expression phenotype of SSA/Ps to better define this cancer precursor. RESULTS RNA sequencing was performed on 5' capped RNA from seven SSA/Ps collected from patients with the serrated polyposis syndrome (SPS) versus eight controls. Highly expressed genes were analyzed by qPCR in additional SSA/Ps, adenomas and controls. The cellular localization and level of gene products were examined by immunohistochemistry in syndromic and sporadic SSA/Ps, adenomatous and hyperplastic polyps and controls. We identified 1,294 differentially expressed annotated genes, with 106 increased ≥10-fold, in SSA/Ps compared to controls. Comparing these genes with an array dataset for adenomatous polyps identified 30 protein coding genes uniquely expressed ≥10-fold in SSA/Ps. Biological pathways altered in SSA/Ps included mucosal integrity, cell adhesion, and cell development. Marked increased expression of MUC17, the cell junction protein genes VSIG1 and GJB5, and the antiapoptotic gene REG4 were found in SSA/Ps, relative to controls and adenomas, were verified by qPCR analysis of additional SSA/Ps (n = 21) and adenomas (n = 10). Immunohistochemical staining of syndromic (n≥11) and sporadic SSA/Ps (n≥17), adenomatous (n≥13) and hyperplastic (n≥10) polyps plus controls (n≥16) identified unique expression patterns for VSIG1 and MUC17 in SSA/Ps. CONCLUSION A subset of genes and pathways are uniquely increased in SSA/Ps, compared to adenomatous polyps, thus supporting the concept that cancer develops by different pathways in these phenotypically distinct polyps with markedly different gene expression profiles. Immunostaining for a subset of these genes differentiates both syndromic and sporadic SSA/Ps from adenomatous and hyperplastic polyps.
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Affiliation(s)
- Don A. Delker
- Department of Medicine, University of Utah, Salt Lake City, Utah, United States of America
| | - Brett M. McGettigan
- Department of Medicine, University of Utah, Salt Lake City, Utah, United States of America
| | - Priyanka Kanth
- Department of Medicine, University of Utah, Salt Lake City, Utah, United States of America
| | - Stelian Pop
- Department of Medicine, University of Utah, Salt Lake City, Utah, United States of America
| | - Deborah W. Neklason
- Huntsman Cancer Institute, University of Utah, Salt Lake City, Utah, United States of America
| | - Mary P. Bronner
- Department of Pathology, University of Utah, Salt Lake City, Utah, United States of America
- Huntsman Cancer Institute, University of Utah, Salt Lake City, Utah, United States of America
| | - Randall W. Burt
- Department of Medicine, University of Utah, Salt Lake City, Utah, United States of America
- Huntsman Cancer Institute, University of Utah, Salt Lake City, Utah, United States of America
| | - Curt H. Hagedorn
- Department of Medicine, University of Utah, Salt Lake City, Utah, United States of America
- Department of Pathology, University of Utah, Salt Lake City, Utah, United States of America
- Huntsman Cancer Institute, University of Utah, Salt Lake City, Utah, United States of America
- University of Arkansas for Medical Sciences, Little Rock, Arkansas, United States of America
- The Central Arkansas Veterans Healthcare System, Little Rock, Arkansas, United States of America
- * E-mail:
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Miwata T, Hiyama T, Oka S, Tanaka S, Shimamoto F, Arihiro K, Chayama K. Clinicopathologic features of hyperplastic/serrated polyposis syndrome in Japan. J Gastroenterol Hepatol 2013; 28:1693-8. [PMID: 23800207 DOI: 10.1111/jgh.12307] [Citation(s) in RCA: 10] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Accepted: 05/30/2013] [Indexed: 12/21/2022]
Abstract
BACKGROUND AND AIM Hyperplastic/serrated polyposis syndrome (HPS) is a condition characterized by multiple hyperplastic/serrated colorectal polyps. The risk of colorectal cancer (CRC) is increased in HPS. The clinicopathologic characteristics of HPS in Japanese patients are unknown. The aim of this study is to clarify the clinicopathologic features of HPS in Japanese patients. METHODS We retrieved records of patients diagnosed with HPS between April 2008 and March 2011 from the endoscopy database of Hiroshima University Hospital. In addition, we mailed a questionnaire to the hospital's 13 affiliated hospitals in July 2012. Data collected from the database and questionnaires included patient age, sex, number of hyperplastic/serrated polyps and tubular adenomas, size of the largest polyp, polyp location, resection for polyps, coexistence of HPS with CRC, and the diagnostic criterion met. RESULTS Of the 73,608 patients who underwent colonoscopy, 10 (0.014%) met the criteria for HPS. The mean age of these patients was 58.3 years, and 6 (60%) were men. No subjects had a first-degree relative with HPS. Four (40%) HPS patients had more than 30 hyperplastic/serrated polyps, and average size of the largest polyp was 19 mm. Three (30%) HPS patients had coexistence of HPS with CRC. In these 3 patients, polyps were observed throughout the colorectum. CONCLUSIONS Although HPS was a rare condition in the overall study population, patients with the disease may have high risk of CRC. HPS should be diagnosed correctly and followed up carefully.
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Affiliation(s)
- Tomohiro Miwata
- Department of Gastroenterology and Metabolism, Graduate School of Biomedical Sciences, Hiroshima University, Hiroshima, Japan
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Álvarez C, Andreu M, Castells A, Quintero E, Bujanda L, Cubiella J, Salas D, Lanas Á, Carballo F, Morillas JD, Hernández C, Jover R, Sarasqueta C, Enriquéz-Navascués JM, Hernández V, Estévez P, Macenlle R, Sala T, Balaguer F, Pellisé M, Moreira L, Gil I, Peris A, González-Rubio F, Ferrández A, Poves C, Ponce M, Grau J, Serradesanferm A, Ono A, Cruzado J, Pérez-Riquelme F, Alonso-Abreu I, Carrillo-Palau M, Santander C, Díaz Tasende J, Herreros A, Cacho G, Barranco LE, Bessa X. Relationship of colonoscopy-detected serrated polyps with synchronous advanced neoplasia in average-risk individuals. Gastrointest Endosc 2013; 78:333-341.e1. [PMID: 23623039 DOI: 10.1016/j.gie.2013.03.003] [Citation(s) in RCA: 53] [Impact Index Per Article: 4.4] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/26/2012] [Accepted: 03/04/2013] [Indexed: 02/08/2023]
Abstract
BACKGROUND Serrated cancers account for 10% to 20% of all colorectal cancers (CRC) and more than 30% of interval cancers. The presence of proximal serrated polyps and large (≥10 mm) serrated polyps (LSP) has been correlated with colorectal neoplasia. OBJECTIVE To evaluate the prevalence of serrated polyps and their association with synchronous advanced neoplasia in a cohort of average-risk population and to assess the efficacy of one-time colonoscopy and a biennial fecal immunochemical test for reducing CRC-related mortality. This study focused on the sample of 5059 individuals belonging to the colonoscopy arm. DESIGN Multicenter, randomized, controlled trial. SETTING The ColonPrev study, a population-based, multicenter, nationwide, randomized, controlled trial. PATIENTS A total of 5059 asymptomatic men and women aged 50 to 69 years. INTERVENTION Colonoscopy. MAIN OUTCOME MEASUREMENTS Prevalence of serrated polyps and their association with synchronous advanced neoplasia. RESULTS Advanced neoplasia was detected in 520 individuals (10.3%) (CRC was detected in 27 [0.5%] and advanced adenomas in 493 [9.7%]). Serrated polyps were found in 1054 individuals (20.8%). A total of 329 individuals (6.5%) had proximal serrated polyps, and 90 (1.8%) had LSPs. Proximal serrated polyps or LSPs were associated with male sex (odds ratio [OR] 2.08, 95% confidence interval [CI], 1.76-4.45 and OR 1.65, 95% CI, 1.31-2.07, respectively). Also, LSPs were associated with advanced neoplasia (OR 2.49, 95% CI, 1.47-4.198), regardless of their proximal (OR 4.15, 95% CI, 1.69-10.15) or distal (OR 2.61, 95% CI, 1.48-4.58) locations. When we analyzed subtypes of serrated polyps, proximal hyperplasic polyps were related to advanced neoplasia (OR 1.61, 95% CI, 1.13-2.28), although no correlation with the location of the advanced neoplasia was observed. LIMITATIONS Pathology criteria for the diagnosis of serrated polyps were not centrally reviewed. The morphology of the hyperplasic polyps (protruded or flat) was not recorded. Finally, because of the characteristics of a population-based study carried out in average-risk patients, the proportion of patients with CRC was relatively small. CONCLUSION LSPs, but not proximal serrated polyps, are associated with the presence of synchronous advanced neoplasia. Further studies are needed to determine the risk of proximal hyperplastic polyps.
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Affiliation(s)
- Cristina Álvarez
- Department of Gastroenterology, Hospital del Mar. Cancer Research Program, IMIM Hospital del Mar Medical Research Institute, Universitat Autònoma de Barcelona Pompeu Fabra University, Barcelona, Catalonia, Spain
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Navarro M, González S, Iglesias S, Capellá G, Rodríguez-Moranta F, Blanco I. Síndrome de poliposis hiperplásica: diversidad fenotípica y asociación a cáncer colorrectal. Med Clin (Barc) 2013; 141:62-6. [DOI: 10.1016/j.medcli.2012.04.024] [Citation(s) in RCA: 8] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/10/2012] [Revised: 04/19/2012] [Accepted: 04/26/2012] [Indexed: 02/08/2023]
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Serrated lesions and hyperplastic (serrated) polyposis relationship with colorectal cancer: classification and surveillance recommendations. Gastrointest Endosc 2013; 77:858-71. [PMID: 23684091 DOI: 10.1016/j.gie.2013.02.016] [Citation(s) in RCA: 13] [Impact Index Per Article: 1.1] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/05/2012] [Accepted: 02/11/2013] [Indexed: 02/08/2023]
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Edelstein DL, Axilbund JE, Hylind LM, Romans K, Griffin CA, Cruz-Correa M, Giardiello FM. Serrated polyposis: rapid and relentless development of colorectal neoplasia. Gut 2013; 62:404-8. [PMID: 22490521 PMCID: PMC3963509 DOI: 10.1136/gutjnl-2011-300514] [Citation(s) in RCA: 76] [Impact Index Per Article: 6.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/23/2022]
Abstract
OBJECTIVE Serrated (hyperplastic) polyposis (SP) is a rare disorder with multiple colorectal hyperplastic polyps and often sessile serrated adenomas/polyps (SSA/P) or adenomas. Although associated with colorectal cancer, the course of SP is not well described. DESIGN 44 patients with SP were studied. The results of 146 colonoscopies with median follow-up of 2.0 years (range 0-30) and a median of 1.0 years (range 0.5-6) between surveillance colonoscopies were evaluated. Findings from oesophogastroduodenoscopy examinations were analysed. RESULTS The mean age at diagnosis of SP was 52.5 ± 11.9 years (range 22-78). In two pedigrees (5%) another family member had SP. None of 22 patients had gastroduodenal polyps. All patients had additional colorectal polyps at surveillance colonoscopy. SSA/P or adenomas were found in 25 patients (61%) at first colonoscopy and 83% at last colonoscopy. Recurrent SSA/P or adenomas occurred in 68% of patients at surveillance colonoscopy. Three patients had colorectal cancer. Eleven patients (25%) underwent surgery (mean time from diagnosis of SP 2.0 ± 0.9 years). After surgery all seven surveyed patients developed recurrent polyps in the retained colorectum (4/7 had SSA/P or adenomas). No association was found between colorectal neoplasia and sex, age at diagnosis of SP or initial number of colorectal polyps. CONCLUSIONS In SP, rapid and unrelenting colorectal neoplasia development continues in the intact colorectum and retained segment after surgery. These findings support the possibility of annual colonoscopic surveillance, consideration for colectomy when SSA/P or adenomas are encountered and frequent postoperative endoscopic surveillance of the retained colorectum.
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Affiliation(s)
- Daniel L. Edelstein
- Department of Medicine, The Johns Hopkins University School of Medicine, Baltimore, Maryland, USA
| | - Jennifer E. Axilbund
- Department of Oncology, The Johns Hopkins University School of Medicine, Baltimore, Maryland, USA
| | - Linda M. Hylind
- Department of Medicine, The Johns Hopkins University School of Medicine, Baltimore, Maryland, USA
| | - Katharine Romans
- Department of Oncology, The Johns Hopkins University School of Medicine, Baltimore, Maryland, USA
| | - Constance A. Griffin
- Department of Pathology, The Johns Hopkins University School of Medicine, Baltimore, Maryland, USA
| | - Marcia Cruz-Correa
- Department of Medicine, The Johns Hopkins University School of Medicine, Baltimore, Maryland, USA,Department of Medicine, University of Puerto Rico, San Juan, Puerto Rico
| | - Francis M. Giardiello
- Department of Medicine, The Johns Hopkins University School of Medicine, Baltimore, Maryland, USA,Department of Oncology, The Johns Hopkins University School of Medicine, Baltimore, Maryland, USA,Department of Pathology, The Johns Hopkins University School of Medicine, Baltimore, Maryland, USA
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Bettington M, Walker N, Clouston A, Brown I, Leggett B, Whitehall V. The serrated pathway to colorectal carcinoma: current concepts and challenges. Histopathology 2013; 62:367-86. [DOI: 10.1111/his.12055] [Citation(s) in RCA: 345] [Impact Index Per Article: 28.8] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/12/2022]
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Abstract
INTRODUCTION Serrated polyposis (SP) is an infrequent colorectal cancer (CRC) predisposition syndrome. An unidentified genetic defect is believed to play a role in this condition. The risk of SP and/or CRC for first-degree relatives (FDRs) is not yet well known. The aim of our study was to determine the incidence of both SP and/or CRC by studying the FDRs of our index SP cases and to propose an appropriate interval for colonoscopy surveillance in this group. METHODS From 2005 to December 2011, we prospectively included all patients from our hospital who fulfilled the SP diagnostic criteria. We interviewed FDRs face to face and offered a colonoscopy to those who were 35 years old or older. The study was carried out with conventional and high-definition colonoscopes and chromoendoscopy with indigo carmine at the discretion of a single endoscopist. The samples were assessed by two pathologists. We reviewed the clinical data for CRC diagnosed previously in FDRs. RESULTS From 2005, we collected all the new cases of SP and offered a colonoscopy to 95 FDRs of 34 pedigrees. We performed colonoscopies on 78 FDRs (82.1%). The incidence of SP in the FDRs was 32% (25 patients). Seventy-six percent of patients were diagnosed with SP as they had any number of serrated polyps proximal to the sigmoid colon. Only one patient was diagnosed with CRC as a result of the screening colonoscopy. 44.1% of our index cases had an FDR with a diagnosis of CRC. CONCLUSION Our series, which is the largest prospective cohort of FDRs published, reports an elevated incidence of SP in FDRs, thus supporting the need for screening colonoscopy in FDR and its inclusion in the guidelines.
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Serrated polyposis is an underdiagnosed and unclear syndrome: the surgical pathologist has a role in improving detection. Am J Surg Pathol 2012; 36:1178-85. [PMID: 22790859 DOI: 10.1097/pas.0b013e3182597f41] [Citation(s) in RCA: 20] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/12/2022]
Abstract
Serrated polyposis syndrome (SPS) is poorly defined and patients have an increased but unspecified risk for colorectal carcinoma through the serrated pathway. Despite this association SPS remains relatively obscure and is therefore likely underrecognized. We determined the frequency of SPS among patients with any serrated polyps (SPs) over a 6-month "index" period, and in doing so we assessed the ability of surgical pathologists to improve SPS detection. Particular attention was given to the index procedure to assess the potential predictive value of the findings resulting from a single colonoscopy. A total of 929 patients with at least 1 SP were identified, 17 of whom (1.8%) were determined to meet World Health Organization criteria for SPS. Nine patients met the first criterion (≥ 5 proximal SPs, 2 of which are > 10 mm); 4 met the third criterion (> 20 SPs of any size distributed throughout the colon); and 4 met both criteria. Although no specific SP size or number at the index procedure was clearly superior in its ability to predict SPS, > 50% of cases would be detected if a cutoff of ≥ 3 SPs or a single SP ≥ 15 mm at the index procedure is used. In summary, SPS is rare but more likely underdiagnosed. Additional studies to address the underlying genetic basis for SPS are ongoing in order to shed further light on this syndrome. Surgical pathologists are in a unique position to assist in this endeavor by identifying those patients who either meet or seem to be at high risk of meeting World Health Organization criteria.
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Sanduleanu S, Masclee AM, Meijer GA. Interval cancers after colonoscopy-insights and recommendations. Nat Rev Gastroenterol Hepatol 2012; 9:550-4. [PMID: 22907162 DOI: 10.1038/nrgastro.2012.136] [Citation(s) in RCA: 46] [Impact Index Per Article: 3.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/07/2023]
Abstract
Several studies have raised warnings about the limited effectiveness of colonoscopy for the prevention of colorectal cancer (CRC), especially of the proximal colon. Two major categories of factors might be responsible for the development of interval cancers, namely technical, endoscopist-dependent factors and biological characteristics of the cancer that lead to more rapid tumour progression. Recognition of endoscopist-dependent factors is critical, as these factors are probably amenable to correction through improved awareness and education of endoscopists, using quality metrics (such as adenoma detection rates and cecal intubation rates) for objective evaluation and feedback. In this article, the current literature regarding the incidence of, and potential explanations for, interval CRCs is outlined. Although there is probably an interaction between technical and biology-related factors--and an attempt to dissect the biology from the technology might be fraught with difficulties--a structured analysis of individual cases of interval cancer might help in the continuous monitoring of the quality of colonoscopy, and ultimately might reduce the number of interval CRCs.
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Affiliation(s)
- Silvia Sanduleanu
- Division of Gastroenterology and Hepatology, Department of Internal Medicine, Maastricht University Medical Center, PO Box 5800, 6202 AZ, Maastricht, The Netherlands.
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Rex DK, Ahnen DJ, Baron JA, Batts KP, Burke CA, Burt RW, Goldblum JR, Guillem JG, Kahi CJ, Kalady MF, O'Brien MJ, Odze RD, Ogino S, Parry S, Snover DC, Torlakovic EE, Wise PE, Young J, Church J. Serrated lesions of the colorectum: review and recommendations from an expert panel. Am J Gastroenterol 2012. [PMID: 22710576 DOI: 10.1038/aig.2012161] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [Abstract] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/07/2023]
Abstract
Serrated lesions of the colorectum are the precursors of perhaps one-third of colorectal cancers (CRCs). Cancers arising in serrated lesions are usually in the proximal colon, and account for a disproportionate fraction of cancer identified after colonoscopy. We sought to provide guidance for the clinical management of serrated colorectal lesions based on current evidence and expert opinion regarding definitions, classification, and significance of serrated lesions. A consensus conference was held over 2 days reviewing the topic of serrated lesions from the perspectives of histology, molecular biology, epidemiology, clinical aspects, and serrated polyposis. Serrated lesions should be classified pathologically according to the World Health Organization criteria as hyperplastic polyp, sessile serrated adenoma/polyp (SSA/P) with or without cytological dysplasia, or traditional serrated adenoma (TSA). SSA/P and TSA are premalignant lesions, but SSA/P is the principal serrated precursor of CRCs. Serrated lesions have a distinct endoscopic appearance, and several lines of evidence suggest that on average they are more difficult to detect than conventional adenomatous polyps. Effective colonoscopy requires an endoscopist trained in the endoscopic appearance of serrated lesions. We recommend that all serrated lesions proximal to the sigmoid colon and all serrated lesions in the rectosigmoid > 5 mm in size, be completely removed. Recommendations are made for post-polypectomy surveillance of serrated lesions and for surveillance of serrated polyposis patients and their relatives.
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Rex DK, Ahnen DJ, Baron JA, Batts KP, Burke CA, Burt RW, Goldblum JR, Guillem JG, Kahi CJ, Kalady MF, O’Brien MJ, Odze RD, Ogino S, Parry S, Snover DC, Torlakovic EE, Wise PE, Young J, Church J. Serrated lesions of the colorectum: review and recommendations from an expert panel. Am J Gastroenterol 2012; 107:1315-29; quiz 1314, 1330. [PMID: 22710576 PMCID: PMC3629844 DOI: 10.1038/ajg.2012.161] [Citation(s) in RCA: 827] [Impact Index Per Article: 63.6] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/06/2023]
Abstract
Serrated lesions of the colorectum are the precursors of perhaps one-third of colorectal cancers (CRCs). Cancers arising in serrated lesions are usually in the proximal colon, and account for a disproportionate fraction of cancer identified after colonoscopy. We sought to provide guidance for the clinical management of serrated colorectal lesions based on current evidence and expert opinion regarding definitions, classification, and significance of serrated lesions. A consensus conference was held over 2 days reviewing the topic of serrated lesions from the perspectives of histology, molecular biology, epidemiology, clinical aspects, and serrated polyposis. Serrated lesions should be classified pathologically according to the World Health Organization criteria as hyperplastic polyp, sessile serrated adenoma/polyp (SSA/P) with or without cytological dysplasia, or traditional serrated adenoma (TSA). SSA/P and TSA are premalignant lesions, but SSA/P is the principal serrated precursor of CRCs. Serrated lesions have a distinct endoscopic appearance, and several lines of evidence suggest that on average they are more difficult to detect than conventional adenomatous polyps. Effective colonoscopy requires an endoscopist trained in the endoscopic appearance of serrated lesions. We recommend that all serrated lesions proximal to the sigmoid colon and all serrated lesions in the rectosigmoid > 5 mm in size, be completely removed. Recommendations are made for post-polypectomy surveillance of serrated lesions and for surveillance of serrated polyposis patients and their relatives.
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Affiliation(s)
| | - Dennis J. Ahnen
- Staff Physician Denver VA Medical Center and Professor of Medicine, University of Colorado School of Medicine
| | | | | | - Carol A. Burke
- Department of Gastroenterology and Hepatology, Digestive Disease Institute, Cleveland Clinic, Cleveland, Ohio
| | - Randall W. Burt
- Division of Gastroenterology, Department of Internal Medicine, University of Utah School of Medicine
| | | | | | - Charles J. Kahi
- Indiana University School of Medicine; Richard L. Roudebush VA Medical Center
| | | | | | - Robert D. Odze
- Brigham and Womens Hospital, Department of Pathology, Harvard Medical School, Boston MA
| | - Shuji Ogino
- Department of Pathology, Brigham and Women’s Hospital and Harvard Medical School, Boston, MA; Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, MA
| | - Susan Parry
- New Zealand Familial GI Cancer Registry, Auckland City Hospital, New Zealand; Department of Gastroenterology, Middlemore Hospital, Auckland, New Zealand
| | - Dale C. Snover
- Department of Pathology, Fairview Southdale Hospital, Edina, MN
| | - Emina Emilia Torlakovic
- Department of Laboratory Medicine and Pathobiology, University Health Network, University of Toronto, Toronto, ON, Canada
| | - Paul E. Wise
- Department of Surgery, Vanderbilt University Medical Center
| | - Joanne Young
- Cancer Council Queensland Senior Research Fellow, Laboratory Head, Familial Cancer Laboratory, Australia
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Phenotype and polyp landscape in serrated polyposis syndrome: a series of 100 patients from genetics clinics. Am J Surg Pathol 2012; 36:876-82. [PMID: 22510757 DOI: 10.1097/pas.0b013e31824e133f] [Citation(s) in RCA: 67] [Impact Index Per Article: 5.2] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/19/2022]
Abstract
Serrated polyposis syndrome (SPS), also known as hyperplastic polyposis, is a syndrome of unknown genetic basis defined by the occurrence of multiple serrated polyps in the large intestine and associated with an increased risk of colorectal cancer (CRC). There are a variety of SPS presentations, which may encompass a continuum of phenotypes modified by environmental and genetic factors. To explore the phenotype of SPS, we recorded the histologic and molecular characteristics of multiple colorectal polyps in patients with SPS recruited between 2000 and 2010 from genetics clinics in Australia, New Zealand, Canada, and the United States. Three specialist gastrointestinal pathologists reviewed the polyps, which they classified into conventional adenomas or serrated polyps, with various subtypes, according to the current World Health Organization criteria. Mutations in BRAF and KRAS and mismatch repair protein expression were determined in a subset of polyps. A total of 100 patients were selected for the study, of whom 58 were female and 42 were male. The total polyp count per patient ranged from 6 to 150 (median 30). The vast majority of patients (89%) had polyposis affecting the entire large intestine. From this cohort, 406 polyps were reviewed. Most of the polyps (83%) were serrated polyps: microvesicular hyperplastic polyps (HP) (n=156), goblet cell HP (n=25), sessile serrated adenoma/polyps (SSA/P) (n=110), SSA/P with cytologic dysplasia (n=28), and traditional serrated adenomas (n=18). A further 69 polyps were conventional adenomas. BRAF mutation was mainly detected in SSA/P with dysplasia (95%), SSA/P (85%), microvesicular HP (76%), and traditional serrated adenoma (54%), whereas KRAS mutation was present mainly in goblet cell HP (50%) and in tubulovillous adenoma (45%). Four of 6 SSA/Ps with high-grade dysplasia showed loss of MLH1/PMS2 expression. CRC was diagnosed in 39 patients who were more often found to have a conventional adenoma compared with patients without CRC (P=0.003). Patients with SPS referred to genetics clinics had a pancolonic disease with a high polyp burden and a high rate of BRAF mutation. The occurrence of CRC was associated with the presence of conventional adenoma.
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Ahn HS, Hong SJ, Kim HK, Yoo HY, Kim HJ, Ko BM, Lee MS. Hyperplastic Polyposis Syndrome Identified with a BRAF Mutation. Gut Liver 2012; 6:280-3. [PMID: 22570761 PMCID: PMC3343170 DOI: 10.5009/gnl.2012.6.2.280] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/17/2010] [Accepted: 11/15/2010] [Indexed: 12/30/2022] Open
Abstract
Hyperplastic polyposis syndrome (HPS) is a rare condition characterized by the presence of numerous hyperplastic polyps (HPs) in the colon and rectum. Patients with HPS have an increased risk of colorectal cancer. This link is associated with gene mutations, especially B type Raf kinase (BRAF). However, a case of HPS associated with gene mutations has seldom been reported in Korea. Here, we describe a case of HPS in which a BRAF mutation was present in a 34-year-old woman. She had more than 110 HPs in the stomach and colorectum, which we removed. All of the polyps were diagnosed histologically as HPs, and no adenomatous or malignant changes were noted. We performed a BRAF and K-ras mutation analysis as well as a microsatellite analysis on the resected colon polyps. BRAF mutations were found in the resected colon polyps, but there was no evidence of K-RAS mutation or microsatellite instability.
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Affiliation(s)
- Hyung Su Ahn
- Digestive Disease Center, Department of Internal Medicine, Soonchunhyang University College of Medicine, Bucheon, Korea
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The relationship between distal and proximal colonic neoplasia: a meta-analysis. J Gen Intern Med 2012; 27:361-70. [PMID: 22065335 PMCID: PMC3286557 DOI: 10.1007/s11606-011-1919-y] [Citation(s) in RCA: 11] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/23/2011] [Revised: 09/29/2011] [Accepted: 10/03/2011] [Indexed: 02/06/2023]
Abstract
OBJECTIVES To investigate the association between proximal colonic neoplasia and distal lesions as a function of the lesion type. The extent to which health, demographic, and study characteristics moderate this association was also examined. DATA SOURCES Google Scholar, Web of Science, Scopus, and PubMed. STUDY ELIGIBILITY CRITERIA Studies allowing the calculation of OR of proximal neoplasia (PN) and proximal advanced neoplasia (PAN) for distal hyperplastic polyps (HP), nonadvanced adenomas (NAA), adenomas (AD), and advanced neoplasia (AN); also, studies for which the proportions of subjects with isolated (i.e., not accompanied by distal lesions) PN (IPN) and PAN (IPAN) over the total number of subjects with PN or PAN could be calculated. STUDY APPRAISAL AND SYNTHESIS METHODS Thirty-two studies were included for calculating OR between proximal neoplasia and distal lesions and 40 studies for proportions of IPN and IPAN. Subgroup analyses were conducted for presence of symptoms, prevalence of PN and PAN, age, proportion of males, geographic region, study design, and demarcation point. RESULTS The association between distal lesions and proximal neoplasia increased with the severity of the distal lesions. Odds of PN were higher in subjects with HP compared to subjects with a normal distal colon. Odds of PN and PAN were higher in subjects with NAA, AD, and AN than in subjects with a normal distal colon. PAN were more strongly associated with distal lesions in asymptomatic populations, in young populations, and in populations with a low prevalence of PAN. In approximately 60% of the subjects with PN and PAN, these neoplasia were isolated. LIMITATIONS The present results may be affected by publication bias and dichotomization in the subgroup analyses. Limitations related to the individual studies include self-selection, lesion misclassification and misses, and technological advances leading to changes in the detection of lesions during the time span of the included studies. CONCLUSIONS AND IMPLICATIONS OF KEY FINDINGS All types of distal lesions are predictive of PN. All types of distal neoplasia are predictive of PAN. The association between distal lesions and proximal neoplasia increases with the severity of the distal lesion. The association between distal lesions and proximal advanced neoplasia is stronger in low-risk groups as compared to high-risk groups.
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Ibrahim AE, Arends MJ. Molecular typing of colorectal cancer: applications in diagnosis and treatment. DIAGNOSTIC HISTOPATHOLOGY 2012; 18:70-80. [DOI: 10.1016/j.mpdhp.2011.11.002] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 07/29/2024]
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Boparai KS, Hazewinkel Y, Dekker E. Serrated polyposis syndrome and the role of serrated polyps in colorectal cancer development. COLORECTAL CANCER 2012. [DOI: 10.2217/crc.11.8] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/21/2022]
Abstract
SUMMARY Serrated polyposis syndrome is characterized by the presence of multiple colorectal serrated polyps and is associated with an increased colorectal cancer risk. The mixture of distinct precursor lesion types and malignancies in serrated polyposis syndrome provides a unique model to study the recently proposed serrated neoplasia pathway. This pathway involves the progression of serrated polyps, that is, hyperplastic polyps, sessile serrated adenoma/polyps and/or traditional serrated adenomas, to colorectal cancer. The early genetic events of this route, as currently identified, are BRAF or KRAS mutations and an enhanced CPG island methylation status of multiple genes. There is evidence to suggest that a proportion of sporadic colorectal cancers originate from serrated polyps, which encompass molecular sequences of events such as hypermethylation of different genes and BRAF mutations. This review discusses the characteristics and clinical relevance of serrated polyps and provides an overview of the clinical aspects and treatment of serrated polyposis syndrome.
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Affiliation(s)
- Karam Singh Boparai
- Department of Gastroenterology & Hepatology, Academic Medical Centre, Amsterdam, The Netherlands
| | - Yark Hazewinkel
- Department of Gastroenterology & Hepatology, Academic Medical Centre, Amsterdam, The Netherlands
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