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Detection of CAF-1/p60 in peripheral blood as a potential biomarker of HNSCC tumors. Oral Oncol 2021; 120:105367. [PMID: 34237585 DOI: 10.1016/j.oraloncology.2021.105367] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/18/2021] [Revised: 04/16/2021] [Accepted: 05/25/2021] [Indexed: 12/20/2022]
Abstract
To date, a very small number of serum biomarkers have been identified for clinical use in squamous carcinomas of the head and neck region. Chromatin Assembly Factor-1 (CAF-1) heterotrimeric complex subunit CAF1/p60 expression levels have been reported to be of prognostic value in Oral Squamous Cell Carcinoma (OSCC), as well as in other human solid tumors. Here our aim was to detect and quantify CAF1/p60 in the peripheral blood of Head and Neck Squamous Cell Carcinoma (HNSCC) patients, and to investigate the possible associations between serum concentration of CAF-1/p60 and HNSCC tumors. A total of 63 HNSCC patients (51 OSCC, 8 OPSCC, 3 laryngeal SCC, and 1 rhinopharynx SCC) and 30 healthy controls were enrolled. The serum levels of CAF-1/p60 were measured by ELISA assay before and after surgery. Serum CAF-1/p60 concentration resulted significantly higher in cancer patients, compared with healthy controls, in pre-surgery samples (P < 0.05). Serum levels of CAF-1/p60 significantly decreased in serum samples taken after surgery (P < 0.05). Our results demonstrated that CAF-1/p60 may be detected in serum, suggesting a role for CAF-1/p60 as potential soluble biomarkers in HNSCC tumors.
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Wan P, Ongkasuwan J, Martinez J, Sandulache V, Deng D, Jiang J, Sikora A, Altman KW. Biomarkers for Malignant Potential in Vocal Fold Leukoplakia: A State of the Art Review. Otolaryngol Head Neck Surg 2020; 164:751-758. [PMID: 32988279 DOI: 10.1177/0194599820957251] [Citation(s) in RCA: 9] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/14/2022]
Abstract
OBJECTIVE To explore biomarkers that are candidates for understanding potential degeneration to malignancy of vocal fold leukoplakia (VFL), with the goal of guiding future diagnostic and treatment recommendations. DATA SOURCES PubMed and Medline search engines. REVIEW METHODS A systematic review was conducted by searching the following key words: vocal fold or laryngeal, coupled with leukoplakia or dysplasia, and combined with the term prognostic markers. We collated the biomarkers and their significance, followed by observing the power of their evidence by assessing the quality of the studies according to guidelines of tumor marker prognostic studies (REMARK). CONCLUSIONS Prognostic biomarkers in the 16 studies are generally divided into 3 categories according to their biological roles: proliferation (Ki-67, CK-1 RS14024 SNP), cell cycle control (P53, p16, cyclin D1, p57kip2, interleukin-10 [IL-10], miR-10a, and miR-34c), cell adhesion, and invasion (neutrophil-to-lymphocyte ratio, OPN/CD44v6 axis, MMP-1, vascular endothelial growth factor A, MMP-9, serpin peptidase inhibitor 1, plasminogen activator, CTNN/B1, β-catenin, NANOG, HERG1). The prognostic use of these biomarkers is limited due to the variable methodologies, study design, assay methods, and statistical analysis performed. IMPLICATIONS FOR PRACTICE Prognostic factors in vocal fold leukoplakia have important clinical implications regarding the potential for malignant degeneration. Although further study is needed, the currently available evidence suggests that p53, p16, cyclin D1, IL-10, NLR, OPN and CD44v6, CTNNB1, and CTTN and FAK might be of particular interest in determining prognosis of VFL as related to malignancy. Future, large, well-designed, prospective studies are expected to determine the prognostic power of these biomarkers before their implementation in routine clinical practice.
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Affiliation(s)
- Ping Wan
- School of Rehabilitation Sciences, Shanghai University of Traditional Chinese Medicine, Shanghai, China
| | - Julina Ongkasuwan
- Department of Otolaryngology, Baylor College of Medicine, Houston, Texas, USA
| | - Julian Martinez
- Department of Otolaryngology, Baylor College of Medicine, Houston, Texas, USA
| | - Vlad Sandulache
- Department of Otolaryngology, Baylor College of Medicine, Houston, Texas, USA
| | - Defeng Deng
- Department of Otolaryngology, Baylor College of Medicine, Houston, Texas, USA
| | - Jack Jiang
- Department of Otolaryngology, University of Wisconsin, Madison, Wisconsin, USA
| | - Andrew Sikora
- Department of Otolaryngology, Baylor College of Medicine, Houston, Texas, USA
| | - Kenneth W Altman
- Department of Otolaryngology, Geisinger Health System, Danville, Pennsylvania, USA
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Jeyasivanesan DL, Mohamed SP, Pandiar D, Basheer S. Immunohistochemical analysis of osteopontin expression in oral squamous cell carcinoma. Indian J Dent Res 2019; 30:539-543. [PMID: 31745049 DOI: 10.4103/ijdr.ijdr_474_17] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/04/2022] Open
Abstract
Background Oral squamous cell carcinoma (OSCC) is the most common malignant neoplasm of the oral cavity. Osteopontin (OPN) has been proved as a biomarker in varying malignant tumors. Only limited studies detail the role of OPN in OSCC. Aims This study aims to demonstrate the expression of OPN in OSCC and to correlate the expression of OPN with the histologic grades of OSCC. Settings and Design This is a retrospective immunohistochemical study in Dravidian population (linguistically Malayalam). Materials and Methods Thirty diagnosed cases of OSCC were subjected to immunohistochemistry using OPN antibody for detection of OPN expression. Ten normal oral mucosal specimens were also stained as controls. Statistical Analysis Used Chi-square test and ANOVA followed by Bonferroni test. Results OPN expression was significantly higher in OSCC patients than in controls. In normal oral mucosal specimens, none of them showed OPN immunoreactivity. A significant difference was observed between total scores and intensities of normal and varying grades of OSCC. A significant difference was also observed between the percentage of positive cells for OPN expression of normal and varying grades of OSCC. However, no significant difference was observed between the percentage of positive cells for OPN expression of well-, moderate-, poorly-differentiated carcinomas. Correlation of OPN expression with lymph node status, site, and sex was found to be statistically insignificant. Conclusion Insights gained from this study may lead to research targeted at the treatment of OSCC.
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Affiliation(s)
| | | | - Deepak Pandiar
- Department of Dentistry, Faculty of Dental Sciences, Institute of Medical Sciences, BHU, Varanasi, Uttar Pradesh, India
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The role of heavy metals and polychlorinated biphenyls (PCBs) in the oncogenesis of head and neck tumors and thyroid diseases: a pilot study. Biometals 2018. [PMID: 29520558 PMCID: PMC5978909 DOI: 10.1007/s10534-018-0091-9] [Citation(s) in RCA: 13] [Impact Index Per Article: 1.9] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/22/2022]
Abstract
Previous literature has highlighted the mechanisms of molecular toxicity induced by substances such as arsenic, cadmium, chromium, nickel, lead, barium and PCBs. The research was carried out on 20 volunteers, all the patients gave their consent to the research: the aim of the study was to evaluate the presence of metals and PCBs in these different matrices (blood and hair), correlating the biochemical data to pathological conditions present, and also to the area in which patients resided. Various quantitative determinations were carried out on samples of blood and hair for 14 heavy metals and on blood samples for 12 PCBs. For the 11 patients the results indicated that blood levels for half of the 14 displayed heavy metals measured considerably higher compared to the reference values, whilst the levels measured in hair evidenced some positive values significantly higher than the maximum reference. Of the 12 PCBs assayed in blood some showed higher positive values compared to the maximum tabular reference (although there is no clear reference quantified in the WHO-2005 report). In the 9 healthy patients heavy metals in the blood were within the expected target range, with those showing positive results (≤ 3 out of 14 heavy metals for each patient) having values only slightly higher than the reference maximum. The levels of 14 heavy metals measured in hair were below thresholds, and levels for the 12 PCBs measured in blood showed negativity or positivity with values close to the minimum benchmarks. The analyses carried out on biological matrices have uncovered important and significant differences between healthy and unhealthy subjects, both qualitative and quantitative differences with respect to heavy metals and PCBs. All patients with head and neck cancer enlisted for the study had heavy metal and PCB blood levels at least twice the maximum reference level. The levels of heavy metals in hair were at least double the maximum reference. In contrast, all healthy volunteers enrolled showed no significant levels for either metals or PCBs.
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Aravind T, Janardhanan M, Rakesh S, Savithri V, Unnikrishnan UG. Immunolocalization of osteopontin in dysplasias and squamous cell carcinomas arising from oral epithelium. J Oral Maxillofac Pathol 2017; 21:18-23. [PMID: 28479681 PMCID: PMC5406806 DOI: 10.4103/0973-029x.203764] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/24/2023] Open
Abstract
Background: Early detection of oral squamous cell carcinoma (OSCC) remains one of the most efficient ways to ensure patient survival and improved quality of life. Although specific biomarkers related to OSCC have been investigated, a useful biomarker that assesses the transition potential of potentially malignant lesion to OSCC remains to be found. Osteopontin (OPN) has been recognized as an important factor in tumorigenesis and their expression in OSCC have been investigated earlier. In the present study, evaluation of OPN expression in premalignant and malignant lesions has been carried out to assess their possible role as a biomarker in the early diagnosis and prognosis of OSCC. Objectives: The objective of this study is to evaluate the role of OPN as a biomarker in the diagnosis and prognosis of OSCC. Materials and Methods: The study group consisted of archival paraffin-embedded blocks of ten cases each of varying grades of OSCC, oral epithelial dysplasias and epithelial hyperplasias. Sections were subjected to immunohistochemical staining for the biomarker OPN. Results: A positive OPN expression was noticed in epithelial dysplasias and SCC arising from the oral epithelium. A progressive increase in the intensity of staining was seen with increasing grades of dysplasias and a decrease in OPN expression with an increase in grades was observed in OSCC. Conclusion: The expression of OPN in full thickness of epithelium in severe dysplasias, carcinoma in situ, and in the superficial epithelium of OSCC suggest the possibility of considering OPN expression in full epithelial thickness in dysplasias as an indicator for malignant transformation.
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Affiliation(s)
- Thara Aravind
- Department of Oral Pathology and Microbiology, Amrita School of Dentistry, AIMS, Amrita Vishwa Vidyapeetham, Kochi, Kerala, India
| | - Mahija Janardhanan
- Department of Oral Pathology and Microbiology, Amrita School of Dentistry, AIMS, Amrita Vishwa Vidyapeetham, Kochi, Kerala, India
| | - S Rakesh
- Department of Oral Pathology and Microbiology, Amrita School of Dentistry, AIMS, Amrita Vishwa Vidyapeetham, Kochi, Kerala, India
| | - Vindhya Savithri
- Department of Oral Pathology and Microbiology, Amrita School of Dentistry, AIMS, Amrita Vishwa Vidyapeetham, Kochi, Kerala, India
| | - U G Unnikrishnan
- Department of Biostatistics, Amrita School of Dentistry, AIMS, Amrita Vishwa Vidyapeetham, Kochi, Kerala, India
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Méry B, Guy JB, Espenel S, Wozny AS, Simonet S, Vallard A, Alphonse G, Ardail D, Rodriguez-Lafrasse C, Magné N. Targeting head and neck tumoral stem cells: From biological aspects to therapeutic perspectives. World J Stem Cells 2016; 8:13-21. [PMID: 26839637 PMCID: PMC4723718 DOI: 10.4252/wjsc.v8.i1.13] [Citation(s) in RCA: 20] [Impact Index Per Article: 2.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/25/2015] [Revised: 11/09/2015] [Accepted: 12/14/2015] [Indexed: 02/06/2023] Open
Abstract
Head and neck squamous cell cancer (HNSCC) is the sixth most common cancer in the world. Effective therapeutic modalities such as surgery, radiation, chemotherapy and combinations of each are used in the management of the disease. In most cases, treatment fails to obtain total cancer cure. In recent years, it appears that one of the key determinants of treatment failure may be the presence of cancer stem cells (CSCs) that escape currently available therapies. CSCs form a small portion of the total tumor burden but may play a disproportionately important role in determining outcomes. CSCs have stem features such as self-renewal, high migration capacity, drug resistance, high proliferation abilities. A large body of evidence points to the fact that CSCs are particularly resistant to radiotherapy and chemotherapy. In HNSCC, CSCs have been increasingly shown to have an integral role in tumor initiation, disease progression, metastasis and treatment resistance. In the light of such observations, the present review summarizes biological characteristics of CSCs in HNSCC, outlines targeted strategies for the successful eradication of CSCs in HNSCC including targeting the self-renewal controlling pathways, blocking epithelial mesenchymal transition, niche targeting, immunotherapy approaches and highlights the need to better understand CSCs biology for new treatments modalities.
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Adamopoulos PG, Kontos CK, Tsiakanikas P, Scorilas A. Identification of novel alternative splice variants of the BCL2L12 gene in human cancer cells using next-generation sequencing methodology. Cancer Lett 2016; 373:119-129. [PMID: 26797417 DOI: 10.1016/j.canlet.2016.01.019] [Citation(s) in RCA: 24] [Impact Index Per Article: 2.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/18/2015] [Revised: 01/09/2016] [Accepted: 01/11/2016] [Indexed: 12/11/2022]
Abstract
The next-generation sequencing (NGS) technology has enabled genome-wide studies, providing massively parallel DNA sequencing. NGS applications constitute a revolution in molecular biology and genetics and have already paved new ways in cancer research. BCL2L12 is an apoptosis-related gene, previously cloned from members of our research group. Like most members of the BCL2 gene family, it is highly implicated in various types of cancer and hematological malignancies. In the present study, we used NGS to discover novel alternatively spliced variants of the apoptosis-related BCL2L12 gene in many human cancer cell lines, after 3'-RACE nested PCR. Extensive computational analysis uncovered new alternative splicing events and patterns, resulting in novel alternative transcripts of the BCL2L12 gene. PCR was then performed to validate NGS data and identify the derived novel transcripts of the BCL2L12 gene. Therefore, 50 novel BCL2L12 splice variants were discovered. Since BCL2L12 is involved in the apoptotic machinery, the quantification of distinct BCL2L12 transcripts in human samples may have clinical applications in different types of cancer.
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Affiliation(s)
| | - Christos K Kontos
- Department of Biochemistry and Molecular Biology, University of Athens, Athens, Greece
| | | | - Andreas Scorilas
- Department of Biochemistry and Molecular Biology, University of Athens, Athens, Greece.
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Chen J, Zhou Q, Zhu C, Zhu M, Tian Y, Li G, Tao X, Zheng H. Functional characterization of OPN in human laryngeal squamous cell carcinoma and its xenograft model in nude mice. Int J Clin Exp Med 2015; 8:164-172. [PMID: 25784985 PMCID: PMC4358440] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/12/2014] [Accepted: 01/14/2015] [Indexed: 06/04/2023]
Abstract
BACKGROUND Osteopontin (OPN) is involved in promotion of cancer cells by regulating various facets of tumor progression such as cell proliferation, angiogenesis and metastasis. To understand the role of OPN in laryngeal squamous cell carcinoma (LSCC), we thus explored the biological function of OPN in LSCC after silencing OPN expression by RNA interference (RNAi). METHOD The OPN expression in tumor tissues of LSCC was determined immunohistochemically in both LSCC and adjacent normal tissues. Lentivirus vector with RNAi small hairpin gene sequence of OPN (named LV-shOPN) was transfected into Hep-2 cells and transplanted into BALB/c-nu mice. After siRNA transfection, the viability of Hep-2 cells was examined by MTS, OPN expression was detected by Western blotting, and tumor angiogenesis was assessed by microvessel densities (MVD). RESULTS The difference of positive rate of OPN in 72 cases LSCC (54 cases, 75.0%) and adjacent normal tissues (15 cases, 20.8%) was statistically significant (P<0.001) and the OPN expression was also significantly correlated with tumor stage, grade and the presence of lymph node. Hep-2 cells infected with LV-shOPN significantly decreased OPN expression, in comparison to cells with LV-shNon transfection (as the control) (P<0.05). The constructed LV-shOPN effectively inhibited the viability of Hep-2 cell and growth of xenograft tumors in nude mice (all P<0.050). The expression of OPN and MVD was significantly decreased in xenograft tumors (all P<0.05). CONCLUSION RNAi silencing of OPN expression can significantly inhibit tumor growth and angiogenesis of Hep-2 cells, and OPN may be considered as one of gene targeting therapy for LSCC.
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Affiliation(s)
- Jianqiu Chen
- Department of Otolaryngology Head and Neck Surgery, General Hospital of Jinan Military RegionJinan 250031, Shandong Province, PR China
| | - Qi Zhou
- Department of Tumor Biological Treatment, The Third Affiliated Hospital, Soochow UniversityChangzhou 213003, Jiangsu Province, China
| | - Chunsheng Zhu
- Department of Otolaryngology Head and Neck Surgery, General Hospital of Jinan Military RegionJinan 250031, Shandong Province, PR China
| | - Minhui Zhu
- Department of Otolaryngology Head and Neck Surgery, Changhai Hospital of The Second Military Medical UniversityShanghai 200433, PR China
| | - Yongsheng Tian
- Department of Otolaryngology Head and Neck Surgery, Aerospace Center Hospital of Beijing universityBeijing 100049, PR China
| | - Guojun Li
- Department of Head and Neck Surgery, U.T. M.D. Anderson Cancer CenterHouston, TX 77030, USA
| | - Xiaofeng Tao
- Department of Radiology, Shanghai Ninth People’s Hospital Affiliated Shanghai Jiaotong University School of MedicineChina
| | - Hongliang Zheng
- Department of Otolaryngology Head and Neck Surgery, Changhai Hospital of The Second Military Medical UniversityShanghai 200433, PR China
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CD147 and Ki-67 overexpression confers poor prognosis in squamous cell carcinoma of oral tongue: a tissue microarray study. Oral Surg Oral Med Oral Pathol Oral Radiol 2015; 119:553-65. [PMID: 25747176 DOI: 10.1016/j.oooo.2014.12.022] [Citation(s) in RCA: 23] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/07/2014] [Revised: 12/17/2014] [Accepted: 12/22/2014] [Indexed: 12/12/2022]
Abstract
OBJECTIVE Squamous cell carcinoma of the oral tongue (SCCOT) exhibits high risk for recurrence and regional metastasis even after surgical resection. We assessed the clinicopathologic and prognostic significance of a group of functionally related biomarkers. STUDY DESIGN We used a tissue microarray consisting of SCCOT from 32 patients for this study. These patients were treated at the University of Texas MD Anderson Cancer Center from 1995 to 2008. Biomarker expression levels were examined by immunohistochemistry and graded semiquantitatively to determine their prognostic significance. RESULTS CD147 and Tp63 expressions were significantly associated with a higher T stage and Ki-67 labeling index, as well as a shorter overall survival (OS) rate. Expression of Tp63 associated positively with poorly differentiated histology. There was significant association of Tp63 with the expression levels of CD147 and Glut-1. Glut-1 overexpression was marginally associated with a higher T stage. There was no prognostic significance of CD44 v6 expression in SCCOT. CONCLUSION SCCOT with CD147 overexpression in combination with high Ki-67 labeling index had poor OS. CD147 and Ki-67 overexpression is associated with aggressive disease with poor prognosis in SCCOT.
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Chen J, Zhou J, Lu J, Xiong H, Shi X, Gong L. Significance of CD44 expression in head and neck cancer: a systemic review and meta-analysis. BMC Cancer 2014; 14:15. [PMID: 24410905 PMCID: PMC3893437 DOI: 10.1186/1471-2407-14-15] [Citation(s) in RCA: 109] [Impact Index Per Article: 9.9] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/21/2013] [Accepted: 01/06/2014] [Indexed: 02/08/2023] Open
Abstract
BACKGROUND CD44 has been reported to be involved with tumor growth and metastasis and has also been implicated as a CSC marker in head and neck squamous cell cancer (HNSCC). However, the prognostic value of CD44 still remains controversial; hence, we investigated the correlation between CD44 and the clinicopathological features of HNSCC by meta-analysis. METHODS A comprehensive search was performed using PubMed, ISI web of Science and China National Knowledge Infrastructure (CNKI) up to April 2013. Only studies with immunohistochemical staining of HNSCC were considered. Data on TNM classification, tumor grade, disease free survival and 3- or 5-year overall survival rate were extracted. RESULTS Thirty studies with 2102 patients met the inclusion criteria for the meta-analysis. Fifteen studies used anti-pan-CD44 antibody, 9 used anti-CD44-v6 antibody, 2 used anti-CD44-v3 and 2 used anti-CD44s antibody, 1 used anti-CD44-v9, and 1 used anti-CD44-v6,-v3 and -v4-5 simultaneously. The total percentage of CD44 expression was 57.8%, with 49.3% in oral cancer patients, 66.4% in pharynx and 54.7% in larynx cancer patients expressing CD44. No significant correlation between clinical features and CD44 expression was revealed for oral cancer patients, but CD44 was shown to be associated with advanced T categories (larynx: RR = 1.33, 95% CI 1.01-1.76; larynx & pharynx RR = 1.21, 95% CI 1.08-1.35), worse N categories (larynx: RR = 2.53, 95% CI 1.99-3.21; larynx & pharynx RR = 1.95, 95% CI 1.35-2.82), higher tumor grades (larynx & pharynx RR = 1.71, 95% CI 1.04-2.79) and 5-year OS rates (larynx: RR = 0.62, 95% CI 0.47-0.83; larynx & pharynx RR = 0.66, 95% CI 0.47-0.94) in patients with laryngeal and pharyngolaryngeal cancer. In stratified analysis, pan-CD44 and CD44-v6 expression were both correlated with 5-year OS rate of patients with laryngeal (CD44: RR = 0.66, 95% CI 0.46-0.95; CD44-v6 RR = 0.53, 95% CI 0.37-0.77) and pharyngolaryngeal cancer (CD44: RR = 0.56, 95% CI 0.34-0.93; CD44-v6 RR = 0.53, 95% CI 0.37-0.77). CONCLUSIONS Our analysis suggested that CD44 is related to worse T category, N category, tumor grade and prognosis, in pharyngeal and laryngeal cancer, but no clear association was revealed between CD44 expression and oral cancer.
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Affiliation(s)
- Jianqiang Chen
- Department of Otorhinolaryngology, Affiliated Cixi Hospital of Wenzhou Medical, College, Cixi 315300, China
| | - Jianding Zhou
- Department of Otorhinolaryngology, Affiliated Cixi Hospital of Wenzhou Medical, College, Cixi 315300, China
| | - Jie Lu
- Department of Otorhinolaryngology, Affiliated Cixi Hospital of Wenzhou Medical, College, Cixi 315300, China
| | - Hua Xiong
- Department of Otorhinolaryngology, Affiliated Cixi Hospital of Wenzhou Medical, College, Cixi 315300, China
| | - Xueli Shi
- Department of Otorhinolaryngology, Affiliated Cixi Hospital of Wenzhou Medical, College, Cixi 315300, China
| | - Liang Gong
- Department of Otorhinolaryngology, Affiliated Cixi Hospital of Wenzhou Medical, College, Cixi 315300, China
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Chai L, Liu H, Zhang Z, Wang F, Wang Q, Zhou S, Wang S. CD44 Expression Is Predictive of Poor Prognosis in Pharyngolaryngeal Cancer: Systematic Review and Meta-Analysis. TOHOKU J EXP MED 2014; 232:9-19. [DOI: 10.1620/tjem.232.9] [Citation(s) in RCA: 17] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/18/2022]
Affiliation(s)
- Liang Chai
- Department of Otorhinolaryngology, First Affiliated Hospital, Medical School, Zhejiang University
| | - Hongyan Liu
- Department of Otorhinolaryngology, First Affiliated Hospital, Medical School, Zhejiang University
| | - Zhili Zhang
- Department of Otorhinolaryngology, First Affiliated Hospital, Medical School, Zhejiang University
| | - Feng Wang
- Department of Otorhinolaryngology, First Affiliated Hospital, Medical School, Zhejiang University
| | - Qingying Wang
- Department of Otorhinolaryngology, First Affiliated Hospital, Medical School, Zhejiang University
| | - Shuihong Zhou
- Department of Otorhinolaryngology, First Affiliated Hospital, Medical School, Zhejiang University
| | - Shenqing Wang
- Department of Otorhinolaryngology, First Affiliated Hospital, Medical School, Zhejiang University
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Szafarowski T, Szczepanski MJ. Cancer stem cells in head and neck squamous cell carcinoma. Otolaryngol Pol 2013; 68:105-11. [PMID: 24837904 DOI: 10.1016/j.otpol.2013.10.010] [Citation(s) in RCA: 12] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/27/2013] [Revised: 10/30/2013] [Accepted: 10/31/2013] [Indexed: 01/24/2023]
Abstract
Recent studies have demonstrated that cancer stem cells (CSC) play an important role in the pathobiology of head and neck squamous cell carcinomas (HNSCC). This subpopulation of undifferentiated, self-renewing cells is responsible for resistance to conventional anti-cancer therapy, cancer recurrence, metastasis and ability to form a heterogeneous tumor. CSC are identified on the basis of specific markers, including membrane proteins or cell enzymes, or by using their self-renewal properties. As their resistance to standard HNSCC treatment may eventually lead to the lack of treatment success, there is an urgent need to better understanding CSC biology and identify them as potential target new treatment modality.
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Affiliation(s)
- Tomasz Szafarowski
- Department of Otorhinolaryngology, Faculty of Medicine and Dentistry, Medical University of Warsaw, Head: prof. dr n. med. Antoni Krzeski, Warsaw, Poland
| | - Miroslaw J Szczepanski
- Department of Otorhinolaryngology, Faculty of Medicine and Dentistry, Medical University of Warsaw, Head: prof. dr n. med. Antoni Krzeski, Warsaw, Poland; Department of Clinical Immunology, University of Medical Sciences in Poznan, Head: prof. dr n. med. Grzegorz Dworacki, Poznan, Poland.
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Sun BS, Li Y, Zhang ZF, You J, Wang CL. Osteopontin combined with CD44v6, a novel prognostic biomarker in non-small cell lung cancer undergoing curative resection. Ann Thorac Surg 2013; 96:1943-51. [PMID: 24094519 DOI: 10.1016/j.athoracsur.2013.07.089] [Citation(s) in RCA: 25] [Impact Index Per Article: 2.1] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/20/2013] [Revised: 07/24/2013] [Accepted: 07/29/2013] [Indexed: 02/06/2023]
Abstract
BACKGROUND Osteopontin (OPN) is identified as one of the leading genes that promote the metastasis of malignant tumor through binding to CD44v6 and integrin. The purpose of the current study was to assess the prognostic significance of OPN and CD44v6 in patients with non-small cell lung cancer (NSCLC). METHODS Tissue microarray was used to detect the expression of OPN and CD44v6 in 159 NSCLC patients undergoing complete pulmonary resection in our hospital between 2003 and 2006. The correlations among OPN, CD44v6, and clinicopathologic data were analyzed using χ(2) testing analysis. The prognostic values of OPN and CD44v6 were evaluated by univariate Kaplan-Meier survival analysis and multivariate Cox proportional hazard model analysis. RESULTS OPN and CD44v6 were both independent predictors for overall survival and disease-free survival. When OPN and CD44v6 were considered together, the predictive range was extended and the sensitivity was improved, especially for those patients with stage I NSCLC. The 6-year overall survival and disease-free survival rates in OPN+ or CD44v6+ patients were 49.1% and 39.6%, respectively, which were significantly lower than those of OPN-/CD44v6- patients (64.4% and 47.7%, respectively), and were higher than those of OPN+/CD44v6+ patients (16.4% and 14.8%, respectively). Stratification into OPN+/CD44v6+, OPN+ or CD44v6+, or OPN-/CD44v6- groups, based on the expression OPN and CD44v6, could efficiently predicted outcomes (p < 0.001) of NSCLC patients. CONCLUSIONS The combination of OPN and CD44v6 is a valuable independent predictor of tumor recurrence and survival in NSCLC patients.
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Affiliation(s)
- Bing-Sheng Sun
- Department of Lung Cancer, Tianjin Cancer Institute and Hospital, Tianjin Medical University, Tianjin Lung Cancer Center, Key Laboratory of Cancer Prevention and Therapy of Tianjin, Tianjin, China
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Abstract
Cancer stem cells (CSCs), also called “cells that start the tumor,” represent in themselves one of the most topical and controversial issues in the field of cancer research. Tumor stem cells are able to self-propagate in vitro (self-renewal), giving rise both to other tumor stem cells and most advanced cells in the line of differentiation (asymmetric division). A final characteristic is tumorigenicity, a fundamental property, which outlines the tumor stem cell as the only cell able to initiate the formation of a tumor when implanted in immune-deficient mice. The hypothesis of a hierarchical organization of tumor cells dates back more than 40 years, but only in 1997, thanks to the work of John Dick and Dominique Bonnet, was there the formal proof of such an organization in acute myeloid leukemia. Following this, many other research groups were able to isolate CSCs, by appropriate selection markers, in various malignancies, such as breast, brain, colon, pancreas, and liver cancers and in melanoma. To date, however, it is not possible to isolate stem cells from all types of neoplasia, particularly in solid tumors. From a therapeutic point of view, the concept of tumor stem cells implies a complete revision of conventional antineoplastic treatment. Conventional cytotoxic agents are designed to target actively proliferating cells. In the majority of cases, this is not sufficient to eliminate the CSCs, which thanks to their reduced proliferative activity and/or the presence of proteins capable of extruding chemotherapeutics from the cell are not targeted. Therefore, the theory of cancer stem cells can pose new paradigms in terms of cancer treatment. Potential approaches, even in the very early experimental stages, relate to the selective inhibition of pathways connected with self-renewal, or more specifically based on the presence of specific surface markers for selective cytotoxic agent vehicles. Finally, some research groups are trying to induce these cells to differentiate, thus making them easier to remove. For all these reasons, we have collected existing literature on head and neck cancer stem cells that correlate the biological characteristics of this subpopulation of cancer cells with the clinical behavior of tumors.
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Affiliation(s)
- Eugenia Allegra
- Otolaryngology - Head and Neck Surgery, University Magna Graecia of Catanzaro, Catanzaro, Italy
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Salehinejad J, Saghafi S, Sharifi N, Zare-Mahmoodabadi R, Saghravanian N, Ghazi N, Shakeri MT. Evaluation of osteopontin and CD44v6 expression in odontogenic cystic lesions by immunohistochemistry. Pathol Res Pract 2012; 208:410-4. [DOI: 10.1016/j.prp.2012.04.005] [Citation(s) in RCA: 9] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/07/2012] [Revised: 03/29/2012] [Accepted: 04/10/2012] [Indexed: 11/24/2022]
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Mannelli G, Gallo O. Cancer stem cells hypothesis and stem cells in head and neck cancers. Cancer Treat Rev 2011; 38:515-39. [PMID: 22197808 DOI: 10.1016/j.ctrv.2011.11.007] [Citation(s) in RCA: 52] [Impact Index Per Article: 3.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/27/2011] [Revised: 11/23/2011] [Accepted: 11/24/2011] [Indexed: 12/26/2022]
Abstract
There is increasing evidence that the growth and spread of cancer is driven by a small subpopulation of cancer cells, defined as cancer stem cells (CSCs). Recent data indicate that the initiation, growth, recurrence and metastasis of cancers are related to the behavior of a small population of malignant cells with properties of stem cells, and information about them are potentially helpful in identifying the target for the tumor's therapeutic elimination. The presence of subpopulation cells with phenotypic and behavioral characteristics corresponding to both normal epithelial stem cells and to cells capable of initiating tumors has been also reported in head and neck squamous cell carcinomas (HNSCCs).
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Affiliation(s)
- Giuditta Mannelli
- First University Clinic of Otorhinolaryngology-Head and Neck Surgery, Director Prof. Oreste Gallo, University of Florence, Azienda Ospedaliera Universitaria Careggi, Via Largo Brambilla 3, 50134 Firenze, Italy.
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Biomarkers predicting malignant progression of laryngeal epithelial precursor lesions: a systematic review. Eur Arch Otorhinolaryngol 2011; 269:1073-83. [DOI: 10.1007/s00405-011-1831-4] [Citation(s) in RCA: 15] [Impact Index Per Article: 1.1] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/11/2011] [Accepted: 10/30/2011] [Indexed: 01/02/2023]
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Marcos CÁ, Alonso-Guervós M, Prado NR, Gimeno TS, Iglesias FD, Hermsen M, Llorente JL. Genetic model of transformation and neoplastic progression in laryngeal epithelium. Head Neck 2011; 33:216-24. [PMID: 20629083 DOI: 10.1002/hed.21432] [Citation(s) in RCA: 17] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/12/2022] Open
Abstract
BACKGROUND The aim of this study was to analyze genetic alterations in the transformation-progression model of laryngeal tumors. METHODS Copy number changes of 37 genes were analyzed by multiple ligation-dependent probe amplification (MLPA) in 94 tissue samples. RESULTS In the smoker normal mucosa group TP53 loss was predominant, whereas in the precursor lesions CDKN2A loss and CDKN2D gain were most frequent. Precursor lesions with progression presented CTNNB1 loss. In the carcinoma group the most common changes were CDKN2A, MLH1, CTNNB1, and CASP6 losses and RECQL4, CCND1, and EMS1 gains. Positive lymph node primary tumors were related to TP53, IL1A, and RB1 losses and STK11 gain. The lymph node metastases differed from their corresponding primary tumor in LMNA, RECQL4, and IGF1R losses, and N33 and CDKN2D gains. CONCLUSIONS Genetic changes and new key genes were found to be associated with specific steps. We included new steps, not presented in the classic models: normal mucosa tobacco exposed, positive lymph node primary tumor, and corresponding lymph node metastases.
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Affiliation(s)
- César Álvarez Marcos
- Department of Otorhinolaryngology, Hospital Universitario Central de Asturias, Oviedo, Asturias, Spain
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Wang SJ, Bourguignon LYW. Role of hyaluronan-mediated CD44 signaling in head and neck squamous cell carcinoma progression and chemoresistance. THE AMERICAN JOURNAL OF PATHOLOGY 2011; 178:956-63. [PMID: 21356346 DOI: 10.1016/j.ajpath.2010.11.077] [Citation(s) in RCA: 104] [Impact Index Per Article: 7.4] [Reference Citation Analysis] [Abstract] [Track Full Text] [Subscribe] [Scholar Register] [Received: 08/01/2010] [Revised: 10/24/2010] [Accepted: 11/16/2010] [Indexed: 01/22/2023]
Abstract
Head and neck squamous cell carcinoma (HNSCC) is an aggressive malignancy that may involve the oral cavity, pharynx, larynx, and paranasal sinuses. The mechanisms of tumor progression underlying the clinical behavior of HNSCC remain unclear. CD44 comprises a family of transmembrane receptors that can give rise to multiple CD44 variant isoforms. Hyaluronan (HA), a major extracellular matrix component is the primary ligand for CD44 receptors. HA and CD44 signaling play an important role in HNSCC progression. Several CD44 variant isoforms (including v3-, v6-, and v10-containing isoforms) are associated with advanced disease, possibly through unique growth factor interactions with binding domains in the inserted variant regions of the cytoplasmic domain of CD44. In HNSCC, HA mediates the formation of a complex including CD44 and the epidermal growth factor receptor (EGFR) which is overexpressed in a large proportion of HNSCCs. Downstream effectors under EGFR regulation are activated, promoting promote cell growth and tumor survival. The leukemia-associated Rho-guanine nucleotide exchange factor (LARG) also associates with CD44 and EGFR to promote several Ras and RhoA pathway effectors, leading to cell migration, growth, and tumor survival. The secretion of matrix metalloproteinases, necessary for tumor cell invasion, is also regulated by these HA/CD44-mediated pathways. Finally, EGFR-mediated pathways play major roles in the HA/CD44 promotion of chemoresistance in HNSCC. Understanding HA/CD44-mediated signaling pathways may lead to improved treatment of HNSCC.
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Affiliation(s)
- Steven J Wang
- Department of Otolaryngology-Head and Neck Surgery, University of California at San Francisco, San Francisco, California 94115, USA.
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Sayed SI, Dwivedi RC, Katna R, Garg A, Pathak KA, Nutting CM, Rhys-Evans P, Harrington KJ, Kazi R. Implications of understanding cancer stem cell (CSC) biology in head and neck squamous cell cancer. Oral Oncol 2011; 47:237-43. [PMID: 21382740 DOI: 10.1016/j.oraloncology.2011.02.009] [Citation(s) in RCA: 51] [Impact Index Per Article: 3.6] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/04/2010] [Revised: 02/05/2011] [Accepted: 02/07/2011] [Indexed: 12/17/2022]
Abstract
Head and neck squamous cell cancer (HNSCC) is the sixth most common cancer in the world. Effective therapeutic modalities such as surgery, radiation, chemotherapy and combinations of each are used in the management of this disease. Efforts are ongoing throughout the world to improve early detection and prevention of HNSCCs. Often, treatment fails to obtain total cancer cure and this is more likely with advanced stage disease. In recent years it appears that one of the key determinants of treatment failure may be the presence of cancer stem cells (CSC) that 'escape' currently available therapies. CSCs form a minute portion of the total tumour burden but may play a disproportionately important role in determining outcomes. Molecular mechanisms which underlie the genesis of CSCs are yet not fully understood and their detection within the total tumour bulk remains a challenge. Specific markers like Aldehyde dehydrogenase 1 (ALDH1), CD44 and Bmi-1 have shown early promising results both in CSC detection and in guiding treatment protocols. CSCs have been shown to be relatively resistant to standard treatment modalities. It is hoped that developing robust in vitro and in vivo experimental models of CSCs might provide a means of devising more effective therapeutic strategies.
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Affiliation(s)
- Suhail I Sayed
- ENT Dept., Grant Medical College, B.R. Ambedkar Road, Byculla, Mumbai 8, India.
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Nankivell P, Weller M, McConkey C, Paleri V, Mehanna H. Biomarkers in laryngeal dysplasia: A systematic review. Head Neck 2010; 33:1170-6. [DOI: 10.1002/hed.21592] [Citation(s) in RCA: 22] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/24/2010] [Revised: 07/26/2010] [Accepted: 07/27/2010] [Indexed: 12/19/2022] Open
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Chien CY, Su CY, Chuang HC, Fang FM, Huang HY, Chen CH, Chen CM, Huang CC. Comprehensive study on the prognostic role of osteopontin expression in oral squamous cell carcinoma. Oral Oncol 2009; 45:798-802. [PMID: 19213594 DOI: 10.1016/j.oraloncology.2008.12.006] [Citation(s) in RCA: 27] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/02/2008] [Revised: 12/07/2008] [Accepted: 12/08/2008] [Indexed: 12/28/2022]
Abstract
Osteopontin is a tumor-associated protein that promotes tumor development and metastasis. The preoperative blood samples of 94 oral squamous cell carcinoma (OSCC) patients and 28 healthy individuals were analyzed for plasma osteopontin levels, and another 256 paraffin-embedded OSCC specimens were analyzed by osteopontin immunostaining. The patients with advanced tumor (T) stage (T3/T4 vs. T1/T2) and positive nodal (N) status had significantly higher plasma levels of osteopontin (both p<0.001). Positive osteopontin immunostaining also correlated significantly with advanced T stage (p<0.001), positive N status (p<0.001), advanced TNM stage (p<0.001) and male gender (p=0.016). Unfavorable cumulative 5-year overall survival rates correlated significantly with positive osteopontin immunostaining (p<0.001), advanced T stage (p<0.001), positive N status (p<0.001) and advanced TNM stage (p<0.001). However, Cox regression analysis revealed that T stage and N status were independent prognostic factors for survival (both p<0.001) and osteopontin immunostaining was marginally significant for survival (p=0.056). The present study demonstrated that high expression level of osteopontin in either the plasma or the tumor of the patients with OSCC was associated with tumor progression, suggesting that osteopontin expression is an important prognostic factor for OSCC.
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Affiliation(s)
- Chih-Yen Chien
- Department of Otolaryngology, Chang Gung Memorial Hospital-Kaohsiung Medical Center, Chang Gung University College of Medicine, Taiwan
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Spielmann PM, Palmer T, McClymont L. 15-Year review of laryngeal and oral dysplasias and progression to invasive carcinoma. Eur Arch Otorhinolaryngol 2009; 267:423-7. [DOI: 10.1007/s00405-009-1013-9] [Citation(s) in RCA: 27] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/08/2009] [Accepted: 06/04/2009] [Indexed: 11/29/2022]
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Fleskens S, Slootweg P. Grading systems in head and neck dysplasia: their prognostic value, weaknesses and utility. HEAD & NECK ONCOLOGY 2009; 1:11. [PMID: 19432960 PMCID: PMC2686689 DOI: 10.1186/1758-3284-1-11] [Citation(s) in RCA: 74] [Impact Index Per Article: 4.6] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 03/29/2009] [Accepted: 05/11/2009] [Indexed: 11/10/2022]
Abstract
BACKGROUND Grading of dysplasia, including head and neck lesions, continues to be a hotly debated subject. It is subjective and lacks intra- and inter-observer reproducibility due to the insufficiency of validated morphological criteria and the biological nature of dysplasia. Moreover, due to the absence of a consensus, several systems are currently employed. OBJECTIVES The aims of this review are to: 1) Highlight the significance of dysplasia and the importance of a valid method for assessing precursor lesions of the head and neck. 2) Review the different histopathological classification systems for grading intraepithelial lesions of the head and neck. 3) Discuss and review quality requirements for these grading systems. CONCLUSION Regarding the different classification systems, data concerning the WHO classification system are the most available in current literature. There is no simple relationship or overlapping between the classification systems. Further studies should be done to see whether other systems have advantages above the current WHO system and to discover indications that could lead to an universal classification system for intraepithelial lesions of the head and neck.
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Affiliation(s)
- Stijn Fleskens
- Department of Otolaryngology/Head and Neck Surgery, University Medical Center St Radboud, PO Box 9101, 6500 HB Nijmegen, the Netherlands
| | - Piet Slootweg
- Department of Pathology, Radboud University Nijmegen Medical Centre, PO Box 9101, 6500 HB Nijmegen, the Netherlands
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Katsinelos P, Kountouras J, Chatzimavroudis G, Zavos C, Beltsis A, Paroutoglou G, Kamarianis N, Pournaras A, Pilpilidis I. Should inspection of the laryngopharyngeal area be part of routine upper gastrointestinal endoscopy? A prospective study. Dig Liver Dis 2009; 41:283-8. [PMID: 18701359 DOI: 10.1016/j.dld.2008.06.015] [Citation(s) in RCA: 14] [Impact Index Per Article: 0.9] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/03/2008] [Revised: 06/11/2008] [Accepted: 06/26/2008] [Indexed: 12/11/2022]
Abstract
BACKGROUND Examination of the laryngopharyngeal area is not always performed during routine upper gastrointestinal (UGI) endoscopy although initial studies reported pathological findings in 0.9-3.5% of cases. The aim of this study was to prospectively evaluate the accuracy of screening the laryngopharyngeal area during routine UGI endoscopy, before insertion of endoscope into the oesophagus, to avoid a misinterpretation of trauma-related hyperaemia or erythema as signs of laryngitis. METHODS The study included 1297 patients undergoing elective UGI endoscopy, asymptomatic in the laryngopharyngeal area, who underwent a carefully structured examination of the laryngopharyngeal area, videotaped for later blinded review. If pathological findings were suspected, patients were referred to otorhinolaryngologists for additional evaluation. In all cases the DVDs were reviewed by two ear, nose, and throat (ENT) specialists blinded to the endoscopic findings. RESULTS In 1130 (87.12%) patients the examination was performed successfully before insertion of the endoscope into the oesophagus. Gastro-oesophageal reflux disease (GORD) symptoms were present in 254 (22.5%) patients, and erosive oesophagitis was documented in 89 (7.9%) patients. In 44 (3.89%) patients the pathology was suspected by the endoscopist and confirmed by the otorhinolaryngologists. Moreover, 8 (0.71%) patients were found to have laryngeal pathology in the DVDs reviewed by the ENT specialists, further confirmed by laryngoscopy. Sensitivity, specificity, positive, and negative predictive values were 84.61%, 100%, 100%, and 99.26%, respectively, for detecting laryngeal abnormalities by the endoscopist. The most important findings were leukoplakia (n=4), posterior laryngitis (n=16), Reinke's oedema (n=2), and hyperkeratosis of arytenoid folds (n=2). A strict correlation emerged between GORD and posterior laryngitis (75%) and between GORD and Reinke's oedema (100%), documented by pHmetry. A significant association was also observed between heavy smoking and leukoplakia (75%), and hypertrophy of pharyngeal tonsils (100%), respectively. All other findings were lesions without clinical significance. CONCLUSIONS Screening examination of the laryngopharyngeal area should be part of each UGI endoscopy revealing important laryngeal pathology.
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Affiliation(s)
- P Katsinelos
- Department of Endoscopy and Motility Unit, Central Hospital, Thessaloniki, Greece
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Mack B, Gires O. CD44s and CD44v6 expression in head and neck epithelia. PLoS One 2008; 3:e3360. [PMID: 18852874 PMCID: PMC2566597 DOI: 10.1371/journal.pone.0003360] [Citation(s) in RCA: 119] [Impact Index Per Article: 7.0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/24/2008] [Accepted: 09/12/2008] [Indexed: 01/09/2023] Open
Abstract
Background CD44 splice variants are long-known as being associated with cell transformation. Recently, the standard form of CD44 (CD44s) was shown to be part of the signature of cancer stem cells (CSCs) in colon, breast, and in head and neck squamous cell carcinomas (HNSCC). This is somewhat in contradiction to previous reports on the expression of CD44s in HNSCC. The aim of the present study was to clarify the actual pattern of CD44 expression in head and neck epithelia. Methods Expression of CD44s and CD44v6 was analysed by immunohistochemistry with specific antibodies in primary head and neck tissues. Scoring of all specimens followed a two-parameters system, which implemented percentages of positive cells and staining intensities from − to +++ (score = %×intensity; resulting max. score 300). In addition, cell surface expression of CD44s and CD44v6 was assessed in lymphocytes and HNSCC. Results In normal epithelia CD44s and CD44v6 were expressed in 60–95% and 50–80% of cells and yielded mean scores with a standard error of a mean (SEM) of 249.5±14.5 and 198±11.13, respectively. In oral leukoplakia and in moderately differentiated carcinomas CD44s and CD44v6 levels were slightly increased (278.9±7.16 and 242±11.7; 291.8±5.88 and 287.3±6.88). Carcinomas in situ displayed unchanged levels of both proteins whereas poorly differentiated carcinomas consistently expressed diminished CD44s and CD44v6 levels. Lymphocytes and HNSCC lines strongly expressed CD44s but not CD44v6. Conclusion CD44s and CD44v6 expression does not distinguish normal from benign or malignant epithelia of the head and neck. CD44s and CD44v6 were abundantly present in the great majority of cells in head and neck tissues, including carcinomas. Hence, the value of CD44s as a marker for the definition of a small subset of cells (i.e. less than 10%) representing head and neck cancer stem cells may need revision.
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Affiliation(s)
- Brigitte Mack
- Department of Otorhinolaryngology, Head and Neck Surgery, Grosshadern Medical Center, Ludwig-Maximilians-University of Munich, Munich, Germany
| | - Olivier Gires
- Clinical Cooperation Group Molecular Oncology, Helmholtz-Zentrum München, German Research Center for Environmental Health, Head and Neck Research Department, Ludwig-Maximilians-University of Munich, Munich, Germany
- * E-mail:
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