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Serrated precursor lesions

Published on Nov 1, 2011in Pathologe0.546
· DOI :10.1007/S00292-011-1494-3
Gustavo B. Baretton28
Estimated H-index: 28
(TUD: Dresden University of Technology),
Baretton Gb1
Estimated H-index: 1
,
Aust De1
Estimated H-index: 1
Abstract
: The so-called serrated pathway has in recent years been well established as a second route of colorectal carcinogenesis. Sessile serrated polyps, especially sessile serrated adenomas (SSA) and traditional serrated adenomas (TSA) were identified as precursor lesions of this pathway. Activating mutations in either the BRAF (in SSAs) or the KRAS oncogene (in TSAs) have been determined as the initiating molecular alterations, followed by epigenetic methylation of CpG islands in promoter regions of genes which are implicated in cell cycle control or DNA repair. These findings have led to a paradigm shift in gastrointestinal pathology as lesions without cytological dysplasia, such as SSAs and certain forms of hyperplastic polyps, are now accepted to be precancerous lesions. In addition, carcinomas that have developed through the serrated pathway of colorectal carcinogenesis show varying biological behavior relevant for the clinical management of these tumors depending on the molecular aberrations.
  • References (42)
  • Citations (1)
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References42
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#1Mashaal Dhir (Johns Hopkins University)H-Index: 14
#2Shinichi Yachida (Johns Hopkins University)H-Index: 31
Last. Nita Ahuja (Johns Hopkins University)H-Index: 50
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The diagnosis of sessile serrated adenomas (SSAs) is challenging, and there is a great deal of interobserver variability amongst pathologists in differentiating SSAs from hyperplastic polyps (HPPs). The aim of this study was (i) to assess the utility of epigenetic changes such as DNA methylation in differentiating SSAs from HPPs and (ii) to identify common methylation based molecular markers potentially useful for early detection of premalignant neoplastic lesions of gastrointestinal tract. A to...
39 CitationsSource
#1Lydia Kriegl (LMU: Ludwig Maximilian University of Munich)H-Index: 16
#2Jens Neumann (LMU: Ludwig Maximilian University of Munich)H-Index: 25
Last. Thomas Kirchner (LMU: Ludwig Maximilian University of Munich)H-Index: 54
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P16(Ink4a) is an important factor in carcinogenesis and its expression can be linked to oncogene-induced senescence. Oncogene-induced senescence is characterized by growth arrest and occurs as a consequence of oncogene activation due to KRAS or BRAF mutation. It has been shown that the induction of p16(Ink4a) in premalignant lesions and its loss during malignant transformation is an important mechanism in the carcinogenesis of several tumours. Loss of p16(Ink4a) is often caused by CDKN2A promote...
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#1Joanna Gibson (Mayo Clinic)H-Index: 9
#2Hejin P. HahnH-Index: 6
Last. Robert D. OdzeH-Index: 71
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Previous studies have shown that hyperplastic and serrated polyps of the colon show variable degrees of gastric and intestinal differentiation. MUCs are a class of approximately 20 genes that encode high-molecular-weight glycoproteins, or mucopolysaccharides, that are widely expressed in epithelial cells and show organ specificity. The role of MUC in serrated carcinogenesis is unknown. One previously published study suggested that expression of MUC6 is specific for sessile serrated adenoma/polyp...
36 CitationsSource
#1Matthew F. Kalady (Cleveland Clinic)H-Index: 31
#1Matthew F. KaladyH-Index: 22
Last. James M. Church (Cleveland Clinic)H-Index: 77
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BACKGROUND:Hyperplastic polyposis syndrome is a rare syndrome of colorectal cancer predisposition. Patterns of inheritance of hyperplastic polyposis syndrome are not obvious and the clinical definition is relatively arbitrary. We hypothesize that there are multiple phenotypes included in what is cur
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#1Sakiko Hiraoka (Okayama University)H-Index: 16
#2Jun Kato (Okayama University)H-Index: 30
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BACKGROUND & AIMS: There is evidence that serrated polyps (serrated adenomas and hyperplastic polyps) have different malignant potential than traditional adenomas. We used a colonoscopy database to determine the association between the presence of serrated colorectal polyps and colorectal neoplasia. METHODS: We performed a multicenter observational study of 10,199 subjects who underwent first-time colonoscopies. Data collected on study subjects included age and sex and the location, size, and hi...
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Background and aims Sessile serrated adenomas (SSAs) are recognised as precursors to microsatellite unstable adenocarcinomas. This study attempts to estimate the progression rate of SSAs based upon the epidemiology of a large cohort as well as identify relationships to other colorectal polyps. Methods Pathological reports generated at Caris Diagnostics from 290810 colonoscopic specimens on 179111 patients were analysed using computerised algorithms. Results SSAs with or without dysplasia/carcino...
197 CitationsSource
#1Daniela Aust (TUD: Dresden University of Technology)H-Index: 33
#2Gustavo B. Baretton (TUD: Dresden University of Technology)H-Index: 28
Until recently, two major types of colorectal epithelial polyps were distinguished: the adenoma and the hyperplastic polyp. While adenomas—because of their cytological atypia—were recognized as the precursor lesions for colorectal carcinoma, hyperplastic polyps were perceived as harmless lesions without any potential for malignant progression mainly because hyperplastic polyps are missing cytological atypia. Meanwhile, it is recognized that the lesions, formerly classified as hyperplastic, repre...
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#1Fang-I Lu (UBC: University of British Columbia)H-Index: 1
#2De Wet van NiekerkH-Index: 1
Last. Douglas L WebberH-Index: 6
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Sessile serrated adenomas (SSAs) are associated with colorectal carcinomas (CRCs) that demonstrate high microsatellite instability (MSI-H). Currently, SSAs are managed clinically in a similar fashion to adenomatous polyps (APs). We studied the natural history of SSA by analyzing the outcome of previ
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#1Barbara Leggette (Royal Brisbane and Women's Hospital)
#1Barbara A. Leggett (Royal Brisbane and Women's Hospital)H-Index: 69
Last. Vicki L. J. Whitehall (Queensland Health)H-Index: 31
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The "serrated neoplastic pathway" describes the progression of serrated polyps, including sessile serrated adenomas and traditional serrated adenomas, to colorectal cancer. The recognition of this pathway during the last 15 years has led to a paradigm shift in our understanding of the molecular basis of colorectal cancer and significant changes in clinical practice. These findings are particularly relevant to prevention of interval cancers through colonoscopy surveillance programs—an important i...
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#1Mustafa A. Arain (UMN: University of Minnesota)H-Index: 17
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OBJECTIVES:Colon cancers diagnosed in the interval after a complete colonoscopy may occur due to limitations of colonoscopy or due to the development of new tumors, possibly reflecting molecular and environmental differences in tumorigenesis resulting in rapid tumor growth. In a previous study from
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