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1
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Miao YD, Mu LJ, Mi DH. Metabolism-associated genes in occurrence and development of gastrointestinal cancer: Latest progress and future prospect. World J Gastrointest Oncol 2021; 13:758-771. [PMID: 34457185 PMCID: PMC8371517 DOI: 10.4251/wjgo.v13.i8.758] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/22/2021] [Revised: 02/27/2021] [Accepted: 06/23/2021] [Indexed: 02/06/2023] Open
Abstract
Gastrointestinal (GI) cancer remains one of the most prevalent cancers in the world. The occurrence and progression of GI cancer involve multiple events. Metabolic reprogramming is one of the hallmarks of cancer and is intricately related to tumorigenesis. Many metabolic genes are involved in the occurrence and development of GI cancer. Research approaches combining tumor genomics and metabolomics are more likely to provide deeper insights into this field. In this paper, we review the roles of metabolism-associated genes, especially those involved in the regulation pathways, in the occurrence and progression of GI cancer. We provide the latest progress and future prospect into the different molecular mechanisms of metabolism-associated genes involved in the occurrence and development of GI cancer.
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Affiliation(s)
- Yan-Dong Miao
- The First Clinical Medical College, Lanzhou University, Lanzhou 730000, Gansu Province, China
| | - Lin-Jie Mu
- The First Affiliated Hospital, Kunming Medical University, Kunming 650000, Yunnan Province, China
| | - Deng-Hai Mi
- The First Clinical Medical College, Lanzhou University, Lanzhou 730000, Gansu Province, China
- Dean’s Office, Gansu Academy of Traditional Chinese Medicine, Lanzhou 730000, Gansu Province, China
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2
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Booth AL, Taggart MW, Ono Y, Gonzalez RS. From Mixed Hyperplastic/Adenomatous Polyp to Sessile Serrated Lesion: A Long and Winding Road for Long and Winding Crypts. Arch Pathol Lab Med 2020; 145:1289-1296. [PMID: 33351878 DOI: 10.5858/arpa.2020-0591-ra] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 10/15/2020] [Indexed: 11/06/2022]
Abstract
CONTEXT.— During the past 3 decades, numerous articles in the literature have offered terminology, diagnostic criteria, and consensus recommendations regarding the entity currently referred to by the World Health Organization as sessile serrated lesion. Given the many names and various, variably reproducible diagnostic criteria ascribed to sessile serrated lesion, confusion persists for many pathologists and gastroenterologists regarding the diagnosis. This distinction is important, as sessile serrated lesion can progress to malignancy, unlike its main differential diagnosis, hyperplastic polyp. Research studies have shed light on the characteristic architecture and morphology, immunohistochemical patterns, and molecular alterations of sessile serrated lesion, and multiple consensus meetings around the globe have developed their criteria and nomenclature, often clashing or mixing terms. OBJECTIVE.— To provide a narrative review from the entity's early description to our current understanding. DATA SOURCES.— The existing scientific and clinical literature, published texts, medical society recommendations, and specialty consensus guidelines. CONCLUSIONS.— The current World Health Organization criteria are a distillation of this scientific process, but terminology is still a point of contention worldwide.
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Affiliation(s)
- Adam L Booth
- From the Department of Pathology, Beth Israel Deaconess Medical Center, Boston, Massachusetts (Booth, Ono, Gonzalez)
| | - Melissa W Taggart
- The Department of Pathology, Division of Pathology and Laboratory Medicine, The University of Texas M.D. Anderson Cancer Center, Houston (Taggart)
| | - Yuho Ono
- From the Department of Pathology, Beth Israel Deaconess Medical Center, Boston, Massachusetts (Booth, Ono, Gonzalez)
| | - Raul S Gonzalez
- From the Department of Pathology, Beth Israel Deaconess Medical Center, Boston, Massachusetts (Booth, Ono, Gonzalez)
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3
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Batts KP, Atwaibi M, Weinberg DI, McCabe RP. Significance of serrated epithelial change in inflammatory bowel disease. Postgrad Med 2020; 133:66-70. [PMID: 32746680 DOI: 10.1080/00325481.2020.1802138] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 10/23/2022]
Abstract
OBJECTIVES The clinical significance of hyperplastic polyp-like histologic changes in random biopsy samples ('serrated epithelial change' or SEC) from patients with inflammatory bowel disease (IBD) remains uncertain, with some studies suggesting an increased risk of dysplasia and even carcinoma. Controlled studies are few. We studied the significance of SEC on the development of dysplasia in follow-up surveillance of IBD patients in our system. METHODS We identified 94 IBD patients with SEC and 187 IBD patients without SEC identified in index biopsy samples, and retrospectively collated results of follow-up surveillance samples in each group, with the development of dysplasia and/or adenocarcinoma as study endpoints. RESULTS IBD patients with SEC had a 12.8% likelihood of developing dysplasia of any type within IBD-affected areas vs a 4.3% likelihood in non-SEC patients (follow-up in the 1-4 year range for each group). This was significant in univariate analysis (p = 0.013) but not in multivariate analysis, likely due to increased frequency of follow-up sampling in the SEC patients. One cancer developed in each group (p = NS). CONCLUSION Our data, in the context of other studies, neither prove nor conclusively exclude an increased risk of dysplasia in IBD patients with SEC. But cancer risk appears low and continued surveillance at usual intervals seems reasonable.
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Affiliation(s)
- Kenneth P Batts
- Department of Pathology and Lab Medicine, Hospital Pathology Associates, PC , Minneapolis, MN, USA.,Virginia Piper Cancer Institute , Minneapolis, MN, USA
| | | | - David I Weinberg
- Virginia Piper Cancer Institute , Minneapolis, MN, USA.,Department of Gastroenterology, MNGI Digestive Health , Minneapolis, MN, USA
| | - Robert P McCabe
- Virginia Piper Cancer Institute , Minneapolis, MN, USA.,Department of Gastroenterology, MNGI Digestive Health , Minneapolis, MN, USA
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4
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Ünlü M, Uzun E, Bengi G, Sağol Ö, Sarıoğlu S. Molecular characteristics of colorectal hyperplastic polyp subgroups. TURKISH JOURNAL OF GASTROENTEROLOGY 2020; 31:573-580. [PMID: 32915145 DOI: 10.5152/tjg.2020.19322] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 11/22/2022]
Abstract
BACKGROUND/AIMS The importance of hyperplastic polyps during colorectal carcinogenesis is appreciated related to the understanding of serrated pathway. The morphologic subtypes of hyperplastic polyps in carcinogenesis and the nomenculature of lesions with both hyperplastic and adenomatous areas are controversial. We aimed to reveal the molecular properties of hyperplastic polyp subtypes and the molecular changes in polyps containing both hyperplastic and adenomatous areas. Matherial and Methods: 49 hyperplastic polyps [19 microvesicular (MVHP), 19 goblet-rich (GRHP), 11 mucin-poor (MPHP)] and 10 mixed hyperplastic and adenomatous polyps were analysed for KRAS, BRAF mutations and MSI with real-time PCR. RESULTS 68,4% of MVHPs and 81% of MPHPs which were localized in right colon had BRAF mutations. While none of the GRHPs showing a KRAS mutation with a rate of 73% was localized in the ascending colon, 63% of them were localized in the rectosigmoid area. In five (50%) of the mixed polyps, KRAS mutation was detected both in the hyperplastic and adenoma components. There was no BRAF mutation in any of the mixed polyps. However, in two cases, the hyperplastic component was MSI-H and the adenoma area was MSS. CONCLUSION Hyperplastic polyps, even if smaller than 5 mm, are precancerous lesions bearing different mutations. GRHPs with predominant KRAS mutations and MVHPs and MPHSs with predominant BRAF mutations are precancerous. Although the molecular investigations for HPP/SP are not necessary the morphological subtyping should be included if the case is diagnosed with HPP/SP as it will be useful for attracting the gastroenterologist's attention.
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Affiliation(s)
- Mehtat Ünlü
- Department of Pathology, Dokuz Eylül University School of Medicine, İzmir, Turkey
| | - Evren Uzun
- Department of Pathology, Dokuz Eylül University School of Medicine, İzmir, Turkey
| | - Göksel Bengi
- Department of Gastroenterology, Dokuz Eylül University School of Medicine, İzmir, Turkey
| | - Özgül Sağol
- Department of Pathology, Dokuz Eylül University School of Medicine, İzmir, Turkey
| | - Sülen Sarıoğlu
- Department of Pathology, Dokuz Eylül University School of Medicine, İzmir, Turkey
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5
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Altavilla G, Lanza G, Rossi S, Cavazzini L. Morphologic Changes, Mucin Secretion, Carcinoembryonic Antigen (Cea) and Peanut Lectin Reactivity in Colonic Mucosa of Patients at High Risk for Colorectal Cancer. TUMORI JOURNAL 2018; 70:539-48. [PMID: 6397881 DOI: 10.1177/030089168407000612] [Citation(s) in RCA: 6] [Impact Index Per Article: 0.9] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/15/2022]
Abstract
We studied 393 endoscopic colonic biopsies from 72 patients, classified in different groups after assessment of their risk factors, using: histologic, histochemical and immunohistochemical techniques (CEA-PAP and PNA-Px). In high risk patients (Groups A and B) the most relevant modifications were dysplasia with hyposecretion and hyperplasia with sialomucin secretion (TR-type change); in Group A 31 adenomas and 19 hyperplastic polyps also were found. A premalignant nature of dysplasia and predysplastic significance of TR change were suggested: 1) by finding the same alterations in mucosa of Group E (colectomized patients for carcinoma at after 1 year); 2) by increasing expression of CEA and PNA-Px ligands; 3) by their absence in Group D (normal controls). Hyperplastic polyps were confirmed not to be premalignant lesions, but since they had peculiar characteristics (increased CEA and PNA-Px positivity, association with adenomas) it does not seem justified to regard them as lesions unrelated to colorectal cancer, especially when associated with other risk factors. CEA and PNA-Px reactivity correlated well with the risk evaluation and with morphohistochemical changes in the mucosa; the reactivity significantly increased from normal mucosa to dysplasia.
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6
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Abstract
Serrated polyps (SPs) of the colorectum pose a novel challenge to practicing gastroenterologists. Previously thought benign and unimportant, there is now compelling evidence that SPs are responsible for a significant percentage of incident colorectal cancer worldwide. In contrast to conventional adenomas, which tend to be slow growing and polypoid, SPs have unique features that undermine current screening and surveillance practices. For example, sessile serrated polyps (SSPs) are flat, predominately right-sided, and thought to have the potential for rapid growth. Moreover, SSPs are subject to wide variations in endoscopic detection and pathologic interpretation. Unfortunately, little is known about the natural history of SPs, and current guidelines are based largely on expert opinion. In this review, we outline the current taxonomy, epidemiology, and management of SPs with an emphasis on the clinical and public health impact of these lesions.
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Affiliation(s)
| | - Seth D Crockett
- Division of Gastroenterology and Hepatology, University of North Carolina School of Medicine, Chapel Hill, NC, USA
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7
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Kawasaki K, Kurahara K, Yanai S, Oshiro Y, Yao T, Kobayashi H, Nakamura S, Fuchigami T, Sugai T, Matsumoto T. Colonoscopic features and malignant potential of sessile serrated adenomas: comparison with other serrated lesions and conventional adenomas. Colorectal Dis 2016; 18:795-802. [PMID: 26784017 DOI: 10.1111/codi.13276] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/07/2015] [Accepted: 09/24/2015] [Indexed: 12/11/2022]
Abstract
AIM Sessile serrated adenomas/polyps (SSA/Ps) have been proposed as precursors of colorectal cancer. The aims of this investigation were to compare the endoscopic findings of SSA/Ps with those of other serrated lesions and to compare the histological findings of SSA/Ps with those of conventional adenomas. METHOD We retrospectively reviewed colonoscopy records at our institution from 1984 to 2013 and identified cases of endoscopically or surgically resected conventional adenomas and serrated lesions, including SSA/Ps, hyperplastic polyps (HPs) and traditional serrated adenomas (TSAs). The colonoscopic findings of SSA/Ps were compared with those of the other two serrated lesions and histological findings were compared among all groups of lesions. RESULTS There were 79 HPs in 68 patients, 77 SSA/Ps in 63 patients, 167 TSAs in 145 patients and 6324 conventional adenomas in 4129 patients. The inverted type and flat-elevated type were more frequent among SSA/Ps than among the other two types of serrated lesions. Magnifying colonoscopy revealed that a round and open pit pattern, expanded crypt openings and varicose microvascular vessels were more frequently observed among SSA/Ps than among the other types. The incidence of high-grade dysplasia or carcinoma among SSA/Ps (13.0%) was significantly higher than that among HPs (0%, P < 0.001) and equivalent to that among conventional adenomas (12.3%). CONCLUSION SSA/Ps have colonoscopic features distinct from those of HPs and TSAs. The malignant potential of SSA/Ps seems to be equal to that of conventional adenomas.
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Affiliation(s)
- K Kawasaki
- Division of Gastroenterology, Department of Internal Medicine, Iwate Medical University, Morioka, Japan.,Division of Gastroenterology, Matsuyama Red Cross Hospital, Matsuyama, Japan
| | - K Kurahara
- Division of Gastroenterology, Matsuyama Red Cross Hospital, Matsuyama, Japan
| | - S Yanai
- Division of Gastroenterology, Department of Internal Medicine, Iwate Medical University, Morioka, Japan
| | - Y Oshiro
- Department of Pathology, Matsuyama Red Cross Hospital, Matsuyama, Japan
| | - T Yao
- Department of Human Pathology, Juntendo University School of Medicine, Tokyo, Japan
| | - H Kobayashi
- Division of Gastroenterology, Fukuoka Sanno Hospital, Fukuoka, Japan
| | - S Nakamura
- Division of Gastroenterology, Department of Internal Medicine, Iwate Medical University, Morioka, Japan
| | - T Fuchigami
- Division of Gastroenterology, Matsuyama Red Cross Hospital, Matsuyama, Japan
| | - T Sugai
- Department of Diagnostic Pathology, Iwate Medical University, Morioka, Japan
| | - T Matsumoto
- Division of Gastroenterology, Department of Internal Medicine, Iwate Medical University, Morioka, Japan
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8
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Matsuda T, Oka S, Ikematsu H, Matsushita HO, Mori Y, Takeuchi Y, Tamai N, Kawamura T, Chino A, Keum B, Khomvilai S, Uraoka T. Endoscopic diagnosis of colorectal serrated lesions: Current status and future perspectives based on the results of a questionnaire survey. Dig Endosc 2016; 28 Suppl 1:35-42. [PMID: 26864882 DOI: 10.1111/den.12632] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/19/2016] [Revised: 01/31/2016] [Accepted: 02/04/2016] [Indexed: 02/08/2023]
Abstract
Serrated lesions, especially sessile serrated adenoma/polyps (SSA/P) are considered one of the most important precursors of colorectal cancers. However, it is still difficult to endoscopically differentiate SSA/P from hyperplastic polyps. In the present review, we mainly focus on the current status and future perspectives of endoscopic diagnosis of colorectal serrated lesions based on the results of a questionnaire survey and report from the Endoscopic Forum Japan (EFJ) 2015 held in Tokyo in August 2015. The proposed diagnostic strategy recommended for colorectal serrated lesions is as follows. (i) For detection, use of an updated image-enhanced endoscopy system including autofluorescence imaging (AFI) and narrow-band imaging (NBI) may be promising. (ii) For differential diagnosis (hyperplastic polyp or SSA/P) of diminutive, small and large serrated lesions, NBI with magnification and magnifying chromoendoscopy using both indigocarmine and crystal violet should be applied, respectively. (iii) For differential diagnosis of SSA/P (with or without cytological dysplasia), magnifying chromoendoscopy, endocytoscopy and updated AFI system modalities might be promising.
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Affiliation(s)
- Takahisa Matsuda
- Cancer Screening Center, National Cancer Center Hospital, Tokyo, Japan.,Endoscopy Division, National Cancer Center Hospital, Tokyo, Japan
| | - Shiro Oka
- Department of Endoscopy, Hiroshima University Hospital, Hiroshima, Japan
| | - Hiroaki Ikematsu
- Department of Gastrointestinal Oncology & Endoscopy, National Cancer Center Hospital East, Kashiwa, Japan
| | | | - Yuichi Mori
- Digestive Disease Center, Showa University Northern Yokohama Hospital, Yokohama, Japan
| | - Yoji Takeuchi
- Department of Gastrointestinal Oncology, Osaka Medical Center for Cancer and Cardiovascular Diseases, Osaka, Japan
| | - Naoto Tamai
- Department of Endoscopy, The Jikei University School of Medicine, Tokyo, Japan
| | - Takuji Kawamura
- Department of Gastroenterology, Kyoto Second Red Cross Hospital, Kyoto, Japan
| | - Akiko Chino
- Department of Gastroenterology, Cancer Institute Hospital, Japanese Foundation for Cancer Research, Tokyo, Japan
| | - Bora Keum
- Division of Gastroenterology and Hepatology, Department of Internal Medicine, Korea University College of Medicine, Seoul, Korea
| | - Supakij Khomvilai
- Gastrointestinal Endoscopy Excellent Center, Department of Medicine, King Chulalongkorn Memorial Hospital, Chulalongkorn University, Bangkok, Thailand
| | - Toshio Uraoka
- Department of Gastroenterology, National Hospital Organization Tokyo Medical Center, Tokyo, Japan
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9
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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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10
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Crockett SD, Snover DC, Ahnen DJ, Baron JA. Sessile serrated adenomas: an evidence-based guide to management. Clin Gastroenterol Hepatol 2015; 13:11-26.e1. [PMID: 24216467 DOI: 10.1016/j.cgh.2013.10.035] [Citation(s) in RCA: 62] [Impact Index Per Article: 6.2] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/11/2013] [Revised: 10/29/2013] [Accepted: 10/31/2013] [Indexed: 02/07/2023]
Abstract
The concept of serrated colorectal neoplasia and a serrated pathway to colorectal cancer (CRC) is relatively new and continuing to evolve, but it has become highly relevant to gastroenterologists, pathologist, and oncologists alike. Sessile serrated adenomas (SSA) are now thought to be the major precursor lesion of serrated pathway cancers, which represent up to one-third of all sporadic CRC cases. However, despite their increasingly recognized importance, relatively little is known about the epidemiology and natural history of SSAs, and the molecular and epigenetic aspects are incompletely understood. Endoscopists must be aware of the unique features of SSAs so that the practice of colonoscopic screening for CRC can include optimized detection, removal, and appropriate surveillance of SSAs and other serrated precursor lesions. In this review, we discuss the history, epidemiology, and pathologic aspects of SSAs, as well as a recommended management approach and a discussion of uncertainties and opportunities for future research.
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Affiliation(s)
- Seth D Crockett
- Division of Gastroenterology and Hepatology, University of North Carolina School of Medicine, Chapel Hill, North Carolina.
| | - Dale C Snover
- Department of Pathology, Fairview Southdale Hospital, Edina, Minnesota
| | - Dennis J Ahnen
- Division of Gastroenterology, Department of Veterans Affairs Eastern Colorado Health Care System and University of Colorado School of Medicine, Denver, Colorado
| | - John A Baron
- Division of Gastroenterology and Hepatology, University of North Carolina School of Medicine, Chapel Hill, North Carolina
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11
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Abstract
Colonoscopy offers incomplete protection from colorectal cancer, particularly in the right colon. Part of this inadequacy may be related to serrated neoplasia. Serrated polyps of the colorectum are now understood to be a heterogeneous group of polyps, some of which are cancer precursors, such as the sessile serrated adenoma (SSA) and the traditional serrated adenoma (TSA). In contrast to conventional adenomas, there is limited published literature on the epidemiology and natural history of these lesions. Furthermore, existing guidelines regarding screening and surveillance practices for these polyps are based largely on expert opinion without firm evidence. In this review, we describe the current understanding of the molecular biology, histopathology, and endoscopic features of serrated neoplasia of the colorectum, with an emphasis on aspects relevant to the practicing gastroenterologist.
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12
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Verseveld M, Barendse RM, Dawson I, Vos EL, de Graaf EJR, Doornebosch PG. Intramucosal carcinoma of the rectum can be safely treated with transanal endoscopic microsurgery; clinical support of the revised Vienna classification. Surg Endosc 2014; 28:3210-5. [PMID: 24939156 DOI: 10.1007/s00464-014-3593-8] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/16/2013] [Accepted: 05/06/2014] [Indexed: 12/19/2022]
Abstract
AIM The revised Vienna criteria were proposed for classifying rectal neoplasia and subsequent treatment strategies. Restaging intramucosal carcinoma to a non-invasive subgroup seems logical, but clinical support is lacking. In this study, we investigated whether distinction between intramucosal carcinomas (IMC) and rectal adenoma (RA) is of clinical relevance and whether these neoplasms can all be similarly and safely treated by transanal endoscopic microsurgery (TEM). METHODS All consecutive patients with IMC and RA, treated with TEM between 1996 and 2010 in tertiary referral centre for TEM were included. Long-term outcome of 88 IMC was compared to 356 pure rectal adenomas (RA). Local recurrence (LR) rate was the primary endpoint. Risk factors for LR were analysed. RESULTS LR was diagnosed in 7/88 patients (8.0 %) with IMC and in 33/356 patients with primary RA (9.3 %; p = 0.700) and LR-free survival did not differ (p = 0.438). Median time to recurrence was 10 months (IQR IMC 5-30; RA 6-16). Overall recurrence occurred mainly in the first 3 years (38/40; 95 %). None of the LR revealed malignancy on pathological evaluation. No differences could be found in complication rates (IMC 9 %; RA 13 %; p = 0.34). Metastases did not occur in either group. Independent risk factors for LR were irradical margins at final histopathology (HR 2.32; 95 % CI 1.17-4.59; p = 0.016) and more proximal tumours (HR 0.84; 95 % CI 0.77-0.92; P = <0.001). CONCLUSION In this study, IMC of the rectum and RA have similar recurrence rates. This supports the revised Vienna classification. Both entities can be safely treated with TEM.
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Affiliation(s)
- Maria Verseveld
- Department of Surgery, IJsselland Hospital, P.O. Box 960, Capelle aan den IJssel, The Netherlands,
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13
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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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14
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The CIMP Phenotype in BRAF Mutant Serrated Polyps from a Prospective Colonoscopy Patient Cohort. Gastroenterol Res Pract 2014; 2014:374926. [PMID: 24812557 PMCID: PMC4000649 DOI: 10.1155/2014/374926] [Citation(s) in RCA: 36] [Impact Index Per Article: 3.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/22/2013] [Accepted: 02/22/2014] [Indexed: 12/22/2022] Open
Abstract
Colorectal cancers arising via the serrated pathway are often associated with BRAF V600E mutation, CpG island methylator phenotype (CIMP), and microsatellite instability. Previous studies have shown a strong association between BRAF V600E mutation and serrated polyps. This study aims to evaluate CIMP status of all the serrated polyp subtypes and its association with functionally important genes such as MLH1, p16, and IGFBP7. CIMP status and methylation were evaluated using the real-time based MethyLight assay in 154 serrated polyps and 63 conventional adenomas. Results showed that CIMP-high serrated polyps were strongly associated with BRAF mutation and proximal colon. CIMP-high was uncommon in conventional adenomas (1.59%), occurred in 8.25% of hyperplastic polyps (HPs), and became common in sessile serrated adenomas (SSAs) (51.43%). MLH1 methylation was mainly observed in the proximal colon and was significantly associated with BRAF mutation and CIMP-high. The number of samples methylated for p16 and IGFBP7 was the highest in SSAs. The methylation panel we used to detect CIMP is highly specific for CIMP-high cancers. With this panel, we demonstrate that CIMP-high is much more common in SSAs than HPs. This suggests that CIMP-high correlates with increased risk of malignant transformation which was also observed in methylation of functionally important genes.
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16
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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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17
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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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18
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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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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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20
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Leonard DF, Dozois EJ, Smyrk TC, Suwanthanma W, Baron TH, Cima RR, Larson DW. Endoscopic and surgical management of serrated colonic polyps. Br J Surg 2011; 98:1685-94. [PMID: 22034178 DOI: 10.1002/bjs.7654] [Citation(s) in RCA: 17] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 06/02/2011] [Indexed: 12/22/2022]
Abstract
BACKGROUND Serrated polyps are an inhomogeneous group of lesions that harbour precursors of colorectal cancer. Current research has been directed at further defining the histopathological characteristics of these lesions, but definitive treatment recommendations are unclear. The aim was to review the current literature regarding classification, molecular genetics and natural history of these lesions in order to propose a treatment algorithm for surgeons to consider. METHODS The PubMed database was searched using the following search terms: serrated polyp, serrated adenoma, hyperplastic polyp, hyperplastic polyposis, adenoma, endoscopy, surgery, guidelines. Papers published between 1980 and 2010 were selected. RESULTS Sixty papers met the selection criteria. Most authors agree that recommendations regarding endoscopic or surgical management should be based on the polyp's neoplastic potential. Polyps greater than 5 mm should be biopsied to determine their histology so that intervention can be directed accurately. Narrow-band imaging or chromoendoscopy may facilitate the detection and assessment of extent of lesions. Complete endoscopic removal of sessile serrated adenomas in the left or right colon is recommended. Follow-up colonoscopy is recommended in 2-6 months if endoscopic removal is incomplete. If the lesion cannot be entirely removed endoscopically, segmental colectomy is strongly recommended owing to the malignant potential of these polyps. Left-sided lesions are more likely to be pedunculated, making them more amenable to successful endoscopic removal. CONCLUSION Even though the neoplastic potential of certain subtypes of serrated polyp is heavily supported, further studies are needed to make definitive endoscopic and surgical recommendations.
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Affiliation(s)
- D F Leonard
- Division of Colon and Rectal Surgery, Department of Anatomic Pathology, Division of Gastroenterology, Mayo Clinic, Gonda 9 South, 200 First Street SW, Rochester, Minnesota 55905, USA
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21
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Rosty C, Parry S, Young JP. Serrated polyposis: an enigmatic model of colorectal cancer predisposition. PATHOLOGY RESEARCH INTERNATIONAL 2011; 2011:157073. [PMID: 21660283 PMCID: PMC3109311 DOI: 10.4061/2011/157073] [Citation(s) in RCA: 25] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 11/11/2010] [Revised: 02/12/2011] [Accepted: 02/25/2011] [Indexed: 01/30/2023]
Abstract
Serrated polyposis has only recently been accepted as a condition which carries an increased personal and familial risk of colorectal cancer. Described over four decades ago, it remains one of the most underrecognized and poorly understood of all the intestinal polyposes. With a variety of phenotypic presentations, it is likely that serrated polyposis represents a group of diseases rather than a single entity. Further, neoplastic progression in serrated polyposis may be associated with premature aging in the normal mucosa, typified by widespread gene promoter hypermethylation. From this epigenetically altered field, arise diverse polyps and cancers which show a range of molecular features. Despite a high serrated polyp count, only one-third of colorectal cancers demonstrate a BRAF V600E mutation, the molecular hallmark of the canonical serrated pathway, suggesting that though multiple serrated polyps act as a marker of an abnormal mucosa, the majority of CRC in these patients arise within lesions other than BRAF-mutated serrated polyps.
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Affiliation(s)
- Christophe Rosty
- Pathology Queensland and UQ Centre for Clinical Research, Royal Brisbane and Women's Hospital, Herston, QLD 4029, Australia
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22
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Abstract
Until recently, colonic polyps were traditionally classified as either hyperplastic or adenomatous, and only the latter were believed to have the potential to progress to carcinoma. However, it is now appreciated that a subset of serrated polyps also appear to have malignant potential. Serrated polyps are a heterogeneous group of colon polyps that include hyperplastic polyps, sessile serrated adenomas (SSAs), traditional serrated adenomas, and mixed polyps. Insights into these polyps were derived, in part, from studies of patients with the hyperplastic polyposis syndrome. SSAs show a predilection for the right colon, have a distinct histology, and their molecular genetic profile has recently been linked to a pathway for colon tumorigenesis that is characterized by microsatellite instability. Based upon available evidence, it is recommended that patients with serrated adenomas undergo colonoscopic follow-up at the same frequency as for conventional adenomas. It is important that physicians are aware of serrated polyps, particularly serrated adenomas and their relationship to colon cancer, and their proper clinical management.
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Affiliation(s)
- Aravind Sugumar
- Division of Gastroenterology & Hepatology and Division of Oncology, Mayo Clinic and Mayo College of Medicine 200 First Street SW, Rochester, MN 55905 USA
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23
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Buchanan DD, Roberts A, Walsh MD, Parry S, Young JP. Lessons from Lynch syndrome: a tumor biology-based approach to familial colorectal cancer. Future Oncol 2010; 6:539-49. [PMID: 20373868 DOI: 10.2217/fon.10.16] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/22/2022] Open
Abstract
Colorectal cancer (CRC) develops within precursor lesions in the single-celled epithelial lining of the gut. The two most common epithelial lesions are the adenoma and the serrated polyp. CRC is also one of the most familial of the common cancers, and just as there are syndromes associated with increased risk of CRC arising in adenomas, there are also syndromes with increased CRC risk associated with serrated polyps. In this article, we describe the features of such a syndrome, familial serrated neoplasia, which distinguish it from the well-characterized condition Lynch syndrome (or hereditary nonpolyposis CRC), and show that the molecular pathology of tumors forms the basis for this distinction. Lynch syndrome CRC arises almost exclusively within adenomatous precursor lesions, in contrast with familial serrated neoplasia where at least half of the cancers develop in serrated polyps. Finally, rare families exist in which both conditions segregate independently, producing a difficult diagnostic picture.
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McGarrity TJ, Amos C. Less common colorectal cancer predisposition syndromes. Surg Oncol Clin N Am 2009; 18:647-61. [PMID: 19793572 DOI: 10.1016/j.soc.2009.07.005] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 10/20/2022]
Abstract
A variety of syndromes confer increased risk for intestinal polyp development, outside the more commonly occurring syndromes. Each of these uncommon syndromes predispose to pathognomonic histologies that are uncommonly observed. Accurate diagnosis of these syndromes is contingent on higher-level pathology review, evaluation of signs and symptoms beyond sole consideration of the polyps, and collection of a detailed family history. When a genetic mutation can be identified in the proband, the management of intestinal and extra-intestinal cancer screening can be more appropriately tailored.
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Affiliation(s)
- Thomas J McGarrity
- Department of Medicine, Penn State Hershey Medical Center, Hershey, PA 17033-0850, USA.
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25
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Abstract
The fundamental view that colon adenocarcinomas arise only from conventional adenomas has been challenged by the now recognized hyperplastic polyp-serrated adenoma-adenocarcinoma pathway. This article describes the history of the serrated adenoma (both the traditional serrated adenoma and the sessile serrated adenoma) as well as the histology and endoscopic appearance of these lesions in comparison with hyperplastic polyps and mixed polyps. Although the exact pathway is the subject of ongoing research, compelling histologic associations and molecular phenotypes that define the model of the serrated polyp-carcinoma sequence, including microsatellite instability, BRAF/KRAS mutations, and CpG island methylator phenotype, provide strong evidence that this is a genuine pathway. Management of serrated neoplasia of the colon includes careful colonoscopy, complete removal of colonic polyps, sampling fields of diminutive polyps of the rectosigmoid, and basing surveillance on histology of removed polyps.
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26
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Abstract
The colorectal polyposes are uncommon and frequently present diagnostic difficulties. Although the final diagnostic arbiter is the demonstration of a germline mutation, this may not always be demonstrable, and some forms of colorectal polyposis have no known genetic basis. Therefore, an accurate description of the phenotype by the pathologist is central to the establishment of a working diagnosis. This can direct the search for the underlying genetic cause (if any) and is also essential for establishing the magnitude of risk of colorectal malignancy for the patient and the patient's relatives. The pathologist may be provided with only a small and selected sample of endoscopically resected polyps or with prodigious numbers of polyps (too many to sample) when receiving a surgical specimen. Each type of polyposis presents its own particular diagnostic problems that may relate to polyp numbers, gross recognition of small or flat polyps, incomplete development of the full phenotype at the stage of investigation, and the histological classification of unusual or mixed polyps. The aim of this review is to highlight the principles and pitfalls in achieving a comprehensive description of the various types of colorectal polyposis, including classical FAP, attenuated FAP, MUTYH- (formerly MYH-) associated polyposis (MAP), other presentations of multiple adenomas, Peutz-Jeghers syndrome (P-JS), juvenile polyposis syndrome (JPS), Cowden syndrome (CS), hereditary mixed polyposis syndrome (HMPS), and hyperplastic polyposis syndrome (HPS).
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Affiliation(s)
- Jeremy R Jass
- Academic Department of Cellular Pathology, St Mark's Hospital, Imperial College, Wartford Road, London, Harrow, Middlesex HA1 3UJ, UK
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27
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East JE, Saunders BP, Jass JR. Sporadic and syndromic hyperplastic polyps and serrated adenomas of the colon: classification, molecular genetics, natural history, and clinical management. Gastroenterol Clin North Am 2008; 37:25-46, v. [PMID: 18313538 DOI: 10.1016/j.gtc.2007.12.014] [Citation(s) in RCA: 165] [Impact Index Per Article: 9.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/07/2023]
Abstract
There is now strong evidence for an alternative pathway of colorectal carcinogenesis implicating hyperplastic polyps and serrated adenomas. This article briefly reviews the evidence for this serrated pathway, provides diagnostic criteria for clinically significant hyperplastic polyps and allied serrated polyps, and suggests how this information may be translated into safe, effective guidelines for colonoscopy-based colon cancer prevention. Consideration also is given to the definition and management of hyperplastic polyposis syndrome. The currently proposed management plan for serrated polyps is tentative because of incomplete knowledge of the nature and behavior of these polyps. This article highlights key areas warranting further research.
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Affiliation(s)
- James E East
- Wolfson Unit for Endoscopy, St. Mark's Hospital, Watford Road, Harrow, Middlesex HA1 3UJ, UK.
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28
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Jass JR. Gastrointestinal polyposes: clinical, pathological and molecular features. Gastroenterol Clin North Am 2007; 36:927-46, viii. [PMID: 17996798 DOI: 10.1016/j.gtc.2007.08.009] [Citation(s) in RCA: 37] [Impact Index Per Article: 2.1] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/21/2023]
Abstract
This article focuses mainly on noninflammatory epithelial polyposes, particularly the diagnostically important morphological and molecular features of the more recently recognized and/or more poorly understood conditions. One of the most important, but often neglected, of these is hyperplastic polyposis.
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Affiliation(s)
- Jeremy R Jass
- Department of Cellular Pathology, St Mark's Hospital & Imperial College, Watford Road, Harrow, Middlesex HA1 3UJ, UK.
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29
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Kurobe M, Abe K, Kinoshita N, Anami M, Tokai H, Ryu Y, Wen CY, Kanematsu T, Hayashi T. Hyperplastic polyposis associated with two asynchronous colon cancers. World J Gastroenterol 2007; 13:3255-8. [PMID: 17589908 PMCID: PMC4436615 DOI: 10.3748/wjg.v13.i23.3255] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/06/2023] Open
Abstract
We report a patient with hyperplastic polyposis who had two asynchronous colon cancers, a combined adenoma-hyperplastic polyp, a serrated adenoma, and tubular adenomas. Hyperplastic polyposis is thought to be a precancerous lesion; and adenocarcinoma arises from hyperplastic polyposis through the hyperplastic polyp-adenoma-carcinoma sequence. Most polyps in patients with hyperplastic polyposis present as bland-looking hyperplastic polyps, which are regarded as non-neoplastic lesions; however, the risk of malignancy should not be underestimated. In patients with multiple hyperplastic polyps, hyperplastic polyposis should be identified and followed up carefully in order to detect malignant transformation in the early stage.
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Affiliation(s)
- Masaya Kurobe
- Department of Pathology, Nagasaki University Hospital, 1-7-1 Sakamoto, Nagasaki 852-8501, Japan
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30
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Chow E, Lipton L, Lynch E, D'Souza R, Aragona C, Hodgkin L, Brown G, Winship I, Barker M, Buchanan D, Cowie S, Nasioulas S, du Sart D, Young J, Leggett B, Jass J, Macrae F. Hyperplastic polyposis syndrome: phenotypic presentations and the role of MBD4 and MYH. Gastroenterology 2006; 131:30-9. [PMID: 16831587 DOI: 10.1053/j.gastro.2006.03.046] [Citation(s) in RCA: 148] [Impact Index Per Article: 7.8] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/30/2005] [Accepted: 03/23/2006] [Indexed: 12/14/2022]
Abstract
BACKGROUND & AIMS Hyperplastic polyposis syndrome (HPS) is defined phenotypically with multiple, large and/or proximal hyperplastic polyps. There is no known germ-line predisposition. We aimed to characterize the clinicopathologic features of 38 patients with HPS and explore the role of germ-line mutations in the base excision repair genes MBD4 and MYH. METHODS Utilizing clinical databases of The Royal Melbourne Hospital Bowel Cancer Surveillance Service and the Familial Cancer Clinic, 38 patients with HPS were recruited. The patients were analyzed for age at first diagnosis, features of hyperplastic polyposis, family histories of polyposis and colorectal cancer (CRC), coexisting adenomas, serrated adenomas, incidence of CRC, and microsatellite instability in the tumours. Mutation analysis of MBD4 and MYH were performed. RESULTS Serrated adenomas were common (26%), and 19 (50%) of the 38 patients had a first-degree relative with CRC. Family history of HPS was uncommon, with only 2 cases found. Ten patients developed CRC, and 3 required surgery for polyposis. No pathogenic mutations in MBD4 were detected in the 27 patients tested, but 6 single nucleotide polymorphisms of uncertain functional significance were identified. Pathogenic biallelic MYH mutations were detected in 1 patient. CONCLUSIONS Mutations in MBD4 are unlikely to be implicated in HPS; MYH mutations should be studied, especially when adenomas occur in the same patient. The clinical, histopathologic, and molecular findings of this study should contribute to our understanding of HPS and its relationship to the serrated neoplasia pathway.
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Affiliation(s)
- Elizabeth Chow
- Familial Cancer Clinic, Royal Melbourne Hospital, Melbourne, Victoria, Australia.
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Abstract
Serrated neoplasia of the gastro-intestinal tract have peculiar microscopic and molecular features that are still incompletely described. Some serrated polyps seem to be involved in a new carcinogenic pathway in the colon: the serrated neoplasia pathway, with hypermethylation of the cytosine-guanine dinucleotides, located in the promoter of some genes such as h-MLH1, BRAF and MGMT. The natural history of the serrated polyps and their risk for progression to malignancy are still unclear. There is no official guideline for the management of serrated polyps. The aim of this article is to describe the epidemiological, morphological, immunohistochemical and molecular characteristics of the serrated neoplasia of the gastrointestinal tract: hyperplastic polyps, "traditional" serrated adenomas, mixed hyperplastic and adenomatous polyps, sessile serrated adenomas, hyperplastic polyposis and serrated adenocarcinomas.
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Affiliation(s)
- Denis Chatelain
- Service d'Anatomie Pathologique, CHU Amiens, Place Victor Pauchet, 80000 Amiens Cedex 01
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32
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Abstract
Serrated adenomas (SA) of the colorectum show features intermediate between hyperplastic polyps (HP) and adenomas. HP and SA are related lesions and there is now strong evidence for a 'serrated-polyp pathway' to colorectal cancer (CRC) that is largely independent of the classic adenoma-to-carcinoma sequence. A recently recognized lesion in this pathway is a HP variant characterized by relatively large size, atypical histology and proximal location in the colorectum. This HP variant has been given a variety of names in the literature including 'sessile SA' and 'type I SA'. Because this lesion lacks the traditional cytology of colorectal adenoma and in order to avoid confusion with SA, it is referred to in this review as sessile serrated polyp. SA are characterized by a heterogeneous group of changes at the molecular level, but a high proportion have BRAFmutations and DNA methylation. They may develop in HP or sessile serrated polyps, or may arise de novo. In the serratedpolyp pathway, the advent of genetic instability is likely to be an important rate-limiting step that drives rapid neoplastic evolution. Methylation and inactivation of the DNA repair genes MLH1 and MGMT (O-6-methylguanine-DNA methyltransferase) have been proposed as critical steps leading to genetic instability. Stretches of DNA rich in the bases guanine and cytosine (CpG islands; where p represents a phosphodiester bond linking adjacent cytosine and guanine bases) that are normally unmethylated may become methylated in malignant human colorectal tumors. Subsets of colorectal cancers with an unusually high number of methylated CpG islands have been described as having the 'CpG-island-methylator phenotype' It is possible that many, if not all, CRCs with the CpG-island-methylator phenotype evolve through the serrated-polyp pathway that would, therefore, explain approximately 20% of all CRCs. The current lack of guidelines for managing serrated polyps may explain the static incidence of proximal CRC, despite the falling incidence rates for left-sided CRC during the same time period.
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Affiliation(s)
- Jeremy R Jass
- Department of Pathology, McGill University, Duff Medical Building, 3775 University Street, Montreal, Quebec H3A 2B4, Canada.
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33
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Higuchi T, Sugihara K, Jass JR. Demographic and pathological characteristics of serrated polyps of colorectum. Histopathology 2005; 47:32-40. [PMID: 15982321 DOI: 10.1111/j.1365-2559.2005.02180.x] [Citation(s) in RCA: 157] [Impact Index Per Article: 7.9] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/15/2022]
Abstract
AIMS To characterize a series of colorectal polyps, focusing on the clinicopathological features of serrated adenoma (SA), mixed polyp (MP) and the recently recognized sessile serrated adenoma (SSA). METHODS AND RESULTS Eight hundred and ninety-one conventional adenomas (AD), 298 hyperplastic polyps (HP), 27 SSA, 10 MP and 24 traditional SA were obtained from patients during colonoscopic examination. SSA were more likely to be proximally located than other polyps. All SA, MP and SSA and a randomly selected subset of HP (n = 61) and ADs (n = 93) were assessed for expression of mucin, MLH1, MGMT, and Ki67. SSA expressed more MUC5AC than either HP or SA. Loss of MLH1 was not observed in any serrated polyps and in only one AD. Loss of MGMT occurred in 13% of AD, and showed no correlation with histological type, size or location. Loss of MGMT occurred in 24% of SSA, MP and SA (combined), and was more frequent in proximal lesions and larger lesions. SSA had a higher proliferative index than HP. In MP, the proliferative index of the non-dysplastic component was closer to HP than SSA, while the dysplastic component was intermediate between SA and AD. CONCLUSIONS SSA differ from other serrated polyps of colorectum in terms of location, morphology and immunophenotype.
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Affiliation(s)
- T Higuchi
- Department of Pathology, McGill University, Montreal, Quebec, Canada
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34
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Sano Y, Maeda N, Kanzaki A, Fujii T, Ochiai A, Takenoshita S, Takebayashi Y. Angiogenesis in colon hyperplastic polyp. Cancer Lett 2005; 218:223-8. [PMID: 15670900 DOI: 10.1016/s0304-3835(03)00183-6] [Citation(s) in RCA: 7] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/05/2002] [Revised: 01/31/2003] [Accepted: 02/14/2003] [Indexed: 11/20/2022]
Abstract
Despite the significance of tumor angiogenesis and the extensive knowledge on the molecular basis of blood vessel formation in carcinoma of colorectum, no data exist in hyperplastic polyp. This prompted us to examine angiogenesis in hyperplastic polyp. Eleven small hyperplastic polyps, 13 large hyperplastic polyps and their adjacent normal mucosas were included in this study. Angiogenesis was assessed by immunohistochemistry using monoclonal antibody against CD34. Angiogenic factor, thymidine phosphorylase was also examined by immunohistochemistry. Intra-tumoral microvessel density (IMD) in large hyperplastic polyp was significantly higher than that in small hyperplastic polyp (P<0.01) and that in normal mucosa (P<0.01). DAD in small hyperplastic polyp was also significantly higher than that in normal mucosa (P<0.01). Expression of dThdPase was almost observed in stromal cells in normal, small and large hyperplastic polyp. In addition, the proportion of the stromal cells expressing dThdPase in large hyperplastic polyp was significantly higher than that in small hyperplastic polyp and normal tissue (P<0.01, respectively). The proportion of the stromal cells expressing dThdPase in small hyperplastic polyp was significantly higher than that in normal tissue (P<0.01). The present study provides that angiogenesis may have an important role(s) in the development of hyperplastic polyp and dThdPase in stromal cells may support angiogenesis in hyperplastic polyp. Anti-angiogenic therapy might be available for suppression of hyperplastic polyp.
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Affiliation(s)
- Yasushi Sano
- Division of Gastrointestinal Endoscopy, National Cancer Center Hospital East, Chiba, Japan.
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35
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Stellakis MLC, Reddy KM, Arnaout A, Swift RI. Hyperplastic polyps and serrated adenomas: colonoscopic surveillance? Surgeon 2004; 2:112-4. [PMID: 15568437 DOI: 10.1016/s1479-666x(04)80055-6] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 10/20/2022]
Abstract
Hyperplastic polyps are not thought to carry a malignant potential. They are, therefore, not regularly screened by the majority of clinicians. We present two case reports of serrated adenomas that add to a small but expanding body of clinical and histological evidence that suggests a hyperplastic to neoplastic pathway. Regular colonoscopic surveillance may be indicated in at least some cases of hyperplastic polyposis
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Affiliation(s)
- M L C Stellakis
- Colorectal Unit, Mayday University Hospital, 530 London Road, Croydon, London CR7 7YE.
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36
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Ferrández A, Samowitz W, DiSario JA, Burt RW. Phenotypic characteristics and risk of cancer development in hyperplastic polyposis: case series and literature review. Am J Gastroenterol 2004; 99:2012-8. [PMID: 15447765 DOI: 10.1111/j.1572-0241.2004.30021.x] [Citation(s) in RCA: 78] [Impact Index Per Article: 3.7] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/06/2023]
Abstract
OBJECTIVES Hyperplastic polyposis (HP) is a poorly understood condition. The aim of this study is to describe the phenotype and the risk of cancer in HP. METHODS Patients with HP, as defined by the WHO International Classification, were identified through the University of Utah and the Huntsman Cancer Institute databases. Family history was retrieved when possible. RESULTS Fifteen patients were identified (10 M, 5 F) with a mean age at diagnosis of 52.6 +/- 16.4 yr (18-71). Sixty-five colonoscopies were performed (2-11 per person). A median of 90 polyps (16-210) per person and 15 polyps (range, 0-100) per procedure were reported. The median follow-up was 33 months (3-133); no cancer occurred during this period. Polyps were more frequent in the distal than the proximal colon (74%vs 26%; p < 0.001). The median polyp size was 4 mm (1-40 mm). Fifty-one hyperplastic polyps >10 mm were identified in 10 patients (38 proximal, 13 distal; p= 0.089). Forty-eight adenomas were found in 11 patients and were uniformly distributed. Serrated adenomas (n = 3) were found in one patient. A unique patient had 20 large hyperplastic polyps, 24 adenomas, 3 serrated adenomas, and 118 hyperplastic polyps. None of the patients had a first-degree relative with colon cancer. CONCLUSIONS In HP, hyperplastic polyps are more frequently distal colonic, and vary greatly in size and number. Most patients also develop adenomas that are distributed throughout the colon. No cancers developed within 3 yr of follow-up. Colonoscopic surveillance at intervals of 1-3 yr, depending upon the number and size of both adenomatous and hyperplastic polyps, appears prudent.
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Affiliation(s)
- Angel Ferrández
- Department of Prevention and Outreach, Huntsman Cancer Institute, University of Utah, 2000 Circle of Hope, Salt Lake City, UT 84112, USA
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Torlakovic E, Skovlund E, Snover DC, Torlakovic G, Nesland JM. Morphologic reappraisal of serrated colorectal polyps. Am J Surg Pathol 2003; 27:65-81. [PMID: 12502929 DOI: 10.1097/00000478-200301000-00008] [Citation(s) in RCA: 425] [Impact Index Per Article: 19.3] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/07/2023]
Abstract
The "hyperplastic polyp" is considered a benign lesion with no malignant potential, whereas "serrated adenoma" is a precursor of adenocarcinoma. The morphologic complexity of the serrated adenoma varies from being clearly adenomatous to being difficult to distinguish from hyperplastic polyp, which creates a need for more detailed morphologic analysis of all serrated polyps. We evaluated 24 morphologic variables in 289 serrated polyps from the colon and rectum. Cluster analysis and discriminant analysis were performed. A subset of polyps was immunostained for hMLH1 and hMSH2. Major differences were found between right-sided and left-sided polyps. A distinct group of serrated polyps with abnormal proliferation was identified throughout the colon and rectum. These polyps demonstrated decreased expression of hMHL1 and hMSH2 compared with polyps with normal proliferation. Left-sided serrated polyps with normal proliferation further clustered into three groups: vesicular cell-type, goblet cell-type, and mucin-poor-type. We recommend evaluation of the localization, size, and morphologic features when serrated polyps are included in colorectal carcinogenesis research. Polyps with abnormal proliferation are similar to the polyps in "hyperplastic polyposis" and, because of their decreased expression of hMLH1 and hMSH2, may be the subset of polyps associated with the development of colorectal carcinoma via the microsatellite instability pathway.
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Affiliation(s)
- Emina Torlakovic
- Department of Pathology, the Norwegian Radium Hospital, University of Oslo, Norway
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Tonooka T, Sano Y, Fujii T, Kato S, Yoshino T, Fu KI, Hironaka SI, Ochiai A, Yoshida S. Adenocarcinoma in solitary large hyperplastic polyp diagnosed by magnifying colonoscope: report of a case. Dis Colon Rectum 2002; 45:1407-11. [PMID: 12394444 DOI: 10.1007/s10350-004-6434-3] [Citation(s) in RCA: 13] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/08/2023]
Abstract
We report a case of carcinoma in a hyperplastic polyp in a 78-year-old female that was diagnosed before resection using a magnifying colonoscope. The patient presented with fecal occult blood and underwent total colonoscopy, which revealed a 12-mm sessile polyp in the cecum. When seen in magnified view, an irregularly shaped pit was evident at the center of the polyp that was distinct from the asteroid-type pits observed over most of the lesion. We diagnosed this lesion as a hyperplastic polyp with a carcinoma component. The patient underwent endoscopic mucosal resection, and histologic section revealed a well-differentiated intramucosal adenocarcinoma in the hyperplastic polyp. Hyperplastic polyps of the colon are regarded as benign, nonneoplastic lesions. Few have reported carcinomas in or with hyperplastic polyps, and most of those were diagnosed after resection and histologic investigation. The literature suggests a precise observation and consideration of resection for large solitary hyperplastic polyps in the right side of the colon, because the risk of malignancy is high. Magnifying colonoscopy is helpful for observing the surface in detail and for correctly diagnosing and managing the lesion.
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Affiliation(s)
- Toru Tonooka
- Division of Digestive Endoscopy and Gastrointestinal Oncology, National Cancer Center Research Institute East, Chiba, Japan
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Abstract
The significance of multiple hyperplastic polyps in relation to the risk of colon cancer is unknown although recent investigation suggests a causative link. We have prospectively identified a small but distinct group of patients that also suggests an association. These patients have either numerous (usually more than twenty, in sites other than the rectosigmoid alone) or large (greater than 1 cm) hyperplastic polyps, in association with either adenomatous polyps, polyps of mixed pathology or carcinoma of the colon and rectum. Additionally, there is frequently a first or second degree family history of colorectal carcinoma.
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Affiliation(s)
- A. J Renaut
- Colorectal Surgical Unit, Prince of Wales Hospital, Sydney, Australia
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Kanamori T, Itoh M, Yoshimi N. Pressure dye-spray: a simple and reliable method for differentiating adenomas from hyperplastic polyps in the colon. Gastrointest Endosc 2002; 55:695-700. [PMID: 11979252 DOI: 10.1067/mge.2002.123620] [Citation(s) in RCA: 19] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/10/2022]
Abstract
BACKGROUND Based on 10 years of experience with chromoendoscopy, our hypothesis was that colonic adenomas can be differentiated from hyperplastic polyps by use of a high-pressure spray-jet of dye (pressure dye-spray). To test the accuracy of pressure dye-spray, classification of colonic polyps as adenomas and hyperplastic polyps by pressure dye-spray and ordinary colonoscopic findings (shape, size, and color surface appearance) were compared. METHODS Pressure dye-spray chromoendoscopy was performed by using 0.035% indigo carmine, a spray-type cannula, and a water pump. Polyps were first classified as adenomas or hyperplastic polyps by ordinary colonoscopic findings. One or more pressure dye-spray bursts were then focused on the polyp from a distance of 1 to 2 cm. Polyps were classified as adenomas only if oozing of blood was evident; otherwise, they were classified as hyperplastic polyps. A histologic diagnosis was obtained for all polyps, and the results of ordinary colonoscopic findings and pressure dye-spray were compared. RESULTS This study examined 1468 polyps (1201 adenomas, 267 hyperplastic polyps; mean diameter 4 mm). The sensitivities for polyp differentiation with pressure dye-spray and ordinary colonoscopic findings were, respectively, 97.9% and 73.4% (p < 0.0001); specificities were, respectively, 96.6% and 92.1% (p = 0.077). CONCLUSIONS Pressure dye-spray was found to be a reliable technique for differentiation between adenomas and hyperplastic polyps.
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Abstract
The non-inherited gastrointestinal polyposis syndromes represent a group of rare disorders characterized by the presence of multiple, non-adenomatous polyps on the gastrointestinal mucosa occurring in unrelated patients. We present here a review of the clinical and histo- pathological aspects of the syndromes to include the Cronkhite-Canada syndrome, hyperplastic polyposis and lipomatous polyposis. While infrequently encountered, these diseases can have devastating clinical effects that may be aggravated by delays in diagnosis and treatment. Prompt accurate diagnosis and treatment of these uncommon disorders depend on a sound working knowledge of the distinct clinical and pathological features described herein.
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Affiliation(s)
- E M Ward
- Department of Internal Medicine and Division of Gastroenterology and Hepatology, Mayo Clinic, Jacksonville, FL 32224, USA
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Affiliation(s)
- B J Rembacken
- Centre for Digestive Diseases, The General Infirmary at Leeds, United Kingdom.
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Tanaka M, Kusumi T, Sasaki Y, Yamagata K, Ichinohe H, Nishida J, Kudo H. Colonic intra-epithelial carcinoma occurring in a hyperplastic polyp via a serrated adenoma. Pathol Int 2001; 51:215-20. [PMID: 11328539 DOI: 10.1046/j.1440-1827.2001.01177.x] [Citation(s) in RCA: 11] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/20/2022]
Abstract
We present a case of intra-epithelial carcinoma occurring in a serrated adenoma of the colon. The pedunculated polyp, which measured 12 x 10 x 6 mm, was endoscopically removed from the ascending colon of a 78-year-old woman. Histologically, the polyp mainly consisted of serrated adenomatous glands, and had foci of intra-epithelial carcinoma at the top. Hyperplastic (metaplastic) areas were also present in both borders between the serrated adenomatous area and the surrounding normal mucosa. A sequential increase in the degree of dysplasia, and in the number of nuclei positively reactive for Ki-67 and p53 was evident from the hyperplastic areas toward the foci of carcinoma. The polyp described here may represent a carcinogenic potential of hyperplastic polyp via serrated adenoma.
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Affiliation(s)
- M Tanaka
- Department of Pathology, Hirosaki University School of Medicine, 5 Zaifu-Cho, Hirosaki 036-8562, Japan.
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Rashid A, Houlihan PS, Booker S, Petersen GM, Giardiello FM, Hamilton SR. Phenotypic and molecular characteristics of hyperplastic polyposis. Gastroenterology 2000; 119:323-32. [PMID: 10930367 DOI: 10.1053/gast.2000.9361] [Citation(s) in RCA: 174] [Impact Index Per Article: 7.0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/27/2022]
Abstract
BACKGROUND & AIMS Patients with hyperplastic polyposis are reported to have multiple and/or large hyperplastic polyps (HPs) and an increased risk of colorectal cancer, but the phenotype and genetic alterations in hyperplastic polyposis have not been studied in detail. METHODS We evaluated clinical-pathological and molecular characteristics of 129 HPs, 6 serrated adenomas, and 3 admixed hyperplastic-adenomatous polyps from 13 patients with hyperplastic polyposis (more than 20 HPs), 5 patients with a large HP (>/=1 cm in diameter), and 5 patients with multiple HPs (5-10 HPs). RESULTS HPs in the right colon in contrast to the left colorectum had more frequent topographic dysregulation of p21(Waf-1/Cip1) expression (94% vs. 76%, P = 0.03) and of proliferation (92% vs. 53%, P = 0. 0001), but less frequent allelic loss of chromosome 1p (4% vs. 17%, P = 0.03). K-ras mutation was present in 8% of HPs, p53 gene product overexpression in none, and microsatellite instability in 3% without relationship to microsatellite instability in synchronous cancer. Patients with a large HP differed from those with multiple HPs in having a high frequency of right-sided HP (63% vs. 22%, P = 0.01) and of right-sided colon cancer (100% vs. 8%, P = 0.003). Hyperplastic polyposis was associated with a family history of colorectal cancer (P = 0.01) and with loss of chromosome 1p in HP (21% vs. 0%, P = 0.001). CONCLUSIONS A hyperplastic polyp/dysplasia-to-adenocarcinoma sequence can be manifested in 3 distinct phenotypes consisting of patients with hyperplastic polyposis and chromosome 1p allelic loss in some HPs, in contrast to patients who have large, right-sided HPs or small numbers of HPs that lack 1p loss.
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Affiliation(s)
- A Rashid
- Department of Pathology, The Johns Hopkins University School of Medicine, Baltimore, Maryland, USA
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Colorectal carcinomas arising in the hyperplastic polyposis syndrome progress through the chromosomal instability pathway. THE AMERICAN JOURNAL OF PATHOLOGY 2000; 157:385-92. [PMID: 10934143 PMCID: PMC1850120 DOI: 10.1016/s0002-9440(10)64551-8] [Citation(s) in RCA: 42] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 01/14/2023]
Abstract
The hyperplastic polyposis syndrome is characterized by the presence within the colon of multiple large hyperplastic polyps. We describe a case of hyperplastic polyposis syndrome associated with two synchronous carcinomas, one of which arises within a pre-existing hyperplastic lesion. Comparative genomic hybridization was used to determine genetic changes in both carcinomas and several associated hyperplastic lesions. Microsatellite analysis at five loci was performed on carcinomas and representative hyperplastic polyps, and p53 status was analyzed by immunohistochemistry. Both carcinomas showed multiple genetic aberrations, including high level gains of 8q and 13q, and loss of 5q. These changes were not seen in the hyperplastic polyps. Microsatellite instability was not seen in the carcinomas, four separate hyperplastic polyps, the hyperplastic polyp with mild adenomatous change associated with the carcinoma, or a separate serrated adenoma. Allelic imbalance in the cancers at D5S346 and D17S938 suggested allelic loss of both p53 and APC, as well as at the loci D13S263, D13S174, D13S159, and D18S49. An early invasive carcinoma in one hyperplastic polyp stained for p53 protein, but the associated hyperplastic polyp was negative. In this case, neoplastic progression followed the typical genetic pathway of common colorectal carcinoma and occurred synchronously with mutation of p53.
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Biemer-Hüttmann AE, Walsh MD, McGuckin MA, Ajioka Y, Watanabe H, Leggett BA, Jass JR. Immunohistochemical staining patterns of MUC1, MUC2, MUC4, and MUC5AC mucins in hyperplastic polyps, serrated adenomas, and traditional adenomas of the colorectum. J Histochem Cytochem 1999; 47:1039-48. [PMID: 10424888 DOI: 10.1177/002215549904700808] [Citation(s) in RCA: 115] [Impact Index Per Article: 4.4] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/18/2022] Open
Abstract
We studied the distribution of the four human apomucins MUC1, MUC2, MUC4, and MUC5AC in hyperplastic polyps, serrated adenomas, and traditional adenomas of the colorectum using immunohistochemical techniques, with the aim of comparing and contrasting their patterns of expression. A series of 12 hyperplastic polyps, 27 serrated adenomas, and 20 traditional adenomas was studied. No significant change in apomucin expression was observed in traditional adenomas compared with normal colorectal epithelium, except for MUC5AC, which was present in 12 of the adenomas (60%) and only 20% of the normal samples. In both hyperplastic polyps and serrated adenomas, MUC2 and MUC5AC mucin expression was consistently and markedly increased. In 50% of the hyperplastic polyps, MUC4 was reduced but in the remaining cases was similar to normal. Loss of MUC4 expression was observed in all serrated adenomas. MUC1 was not increased in the hyperplastic polyps but increased expression was seen in 17 of the serrated adenomas (63%). Similar altered distribution patterns of MUC2, MUC4, and MUC5AC were seen in hyperplastic polyps and serrated adenomas, whereas traditional adenomas showed little change from normal patterns of expression. Although hyperplastic polyps are commonly defined as benign lesions without neoplastic potential, the similar phenotypes of hyperplastic and serrated adenomas and the existence of mixed polyps suggest that these lesions may represent a histogenetic continuum.
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Affiliation(s)
- A E Biemer-Hüttmann
- Department of Pathology, Mayne Medical School, University of Queensland, Herston, Australia
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Yokoo H, Usman I, Wheaton S, Kampmeier PA. Colorectal polyps with extensive absorptive enterocyte differentiation: histologically distinct variant of hyperplastic polyps. Arch Pathol Lab Med 1999; 123:404-10. [PMID: 10235498 DOI: 10.5858/1999-123-0404-cpweae] [Citation(s) in RCA: 9] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/06/2022]
Abstract
BACKGROUND The histologic classification of colorectal polyps is well established. However, practicing pathologists may still occasionally encounter colorectal polyps that are difficult to classify. We studied 6 colorectal polyps that showed uncommon histologic features that have not been described in the English language literature. MATERIALS AND METHODS The polyps were studied using standard hematoxylin-eosin stain, mucin histochemistry, and electron microscopy. RESULTS The 6 polyps we studied showed extensive papillary and villous structures with alternating villi and crypts. The villi were lined by well-differentiated absorptive cells, whereas the crypts were lined by immature glandular cells, thus mimicking the histology of the small intestinal mucosa. CONCLUSIONS These polyps appear to represent a variant of the hyperplastic polyp, in as much as cellular maturation (immature glandular cells differentiate into the mature surface absorptive cells) is the essential feature distinguishing hyperplastic polyps from adenomas.
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Affiliation(s)
- H Yokoo
- Department of Pathology, Northwestern Memorial Hospital, Chicago, Ill 60611, USA
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Keljo DJ, Weinberg AG, Winick N, Tomlinson G. Rectal cancer in an 11-year-old girl with hyperplastic polyposis. J Pediatr Gastroenterol Nutr 1999; 28:327-32. [PMID: 10067739 DOI: 10.1097/00005176-199903000-00023] [Citation(s) in RCA: 25] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/06/2023]
Affiliation(s)
- D J Keljo
- Department of Pediatrics, University of Texas, Southwestern Medical School Center at Dallas, USA
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Croizet O, Moreau J, Arany Y, Delvaux M, Rumeau JL, Escourrou J. Follow-up of patients with hyperplastic polyps of the large bowel. Gastrointest Endosc 1997; 46:119-23. [PMID: 9283860 DOI: 10.1016/s0016-5107(97)70058-0] [Citation(s) in RCA: 24] [Impact Index Per Article: 0.9] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/05/2023]
Abstract
BACKGROUND Adenomatous colonic polyps are accepted as premalignant lesions. There is controversy regarding the significance of the hyperplastic polyp. The aim of this study was to determine the incidence of further polyps in patients with only hyperplastic polyps on a first colonoscopy in comparison with patients without polyps and with adenomatous polyps. METHODS Ninety patients had only hyperplastic polyps (group I). These patients were paired according to age and sex with subjects having no polyps (group II) and with patients having adenomas (group III). RESULTS Fifty-six patients in group I had at least one follow-up examination. New polyps were found in 46.4% in group I versus 15.5% in group II (p < 0.001) and 50% in group III (NS). In group I, 30.7% of new polyps were hyperplastic and 69.3% were adenomas. In fact, 32.2% of group I patients developed further adenomas (mean 1.5 +/- 0.8 adenomas). These adenomas occurred 1 to 4 years after the first polypectomy (mean 2.4 +/- 0.8 years). Most of these adenomas were small and tubular, but 16.6% were villous or had severe dysplasia. CONCLUSION Patients with hyperplastic polyps were 2.4 times more likely to have further adenomas than were those without polyps.
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Affiliation(s)
- O Croizet
- Department of Gastroenterology, Rangueil Hospital, Toulouse, France
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