Progression of a Sessile Serrated Adenoma to an Early Invasive Cancer Within 8 Months

Oono, Yasuhiro; Fu, Kuang‐I; Nakamura, Hisashi; Iriguchi, Yousuke; Yamamura, Akihiko; Tomino, Yasuhiro; Oda, Johji; Mizutani, Masaru; Takayanagi, Shunsaku; Kishi, Daisuke; Shinohara, Tomoaki; Yamada, Kozo; Matumoto, Jun; Imamura, Kazuhiro

doi:10.1007/s10620-008-0407-7

Cited by 112 publications

(83 citation statements)

References 17 publications

(13 reference statements)

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“…Serrated adenoma and hyperplastic polyps have a greater malignant potential (31). Transformation from serrated polyps to invasive CRC can be rapid (32). In this study, the seroreactivities of the 5-phage peptide clones were significantly higher in the patients with colorectal polyps than in the healthy controls, whereas the seroreactivities of 4 of the 5-phage peptide clones were significantly higher in the CRC patients than in those with colorectal polyps.…”

Section: Discussionmentioning

confidence: 49%

Development of Autoantibody Signatures as Biomarkers for Early Detection of Colorectal Carcinoma

Chang

Wu²,

Cao³

et al. 2011

Clinical Cancer Research

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Purpose: To select autoantibody signatures for early detection of colorectal cancer (CRC). Experimental Design: A phage cDNA expression library was constructed with fresh tumors from 30 CRC patients and biopanned by using serum pools of 20 CRC patients and 20 healthy controls. A classifier was discovered in the training set of 30 CRC patients at stages I and II and 30 matched healthy controls and then blindly validated in an independent set of 60 CRC patients, 60 healthy controls, 52 polyps patients, and 30 autoimmune diseases patients. Expression of proteins was examined by using immunohistochemistry.Results: Five-phage peptide clones showing higher discriminatory power than others in training set were selected for validation. The five-phage peptide classifier was able to discriminate between early CRC patients and healthy controls, with sensitivities of 90.0% to 92.7% and specificities of 91.7% to 93.3%. In those with serum carcinoembryonic antigen less than 5 ng/mL, the classifier was efficient in discriminating CRC from healthy controls, with an area under the curve of 0.975. The classifier was able to discriminate all of the 9 patients with serrated adenoma from healthy controls. Thirteen (43.3%) of the patients with autoimmune diseases were misclassified. Of the five phage peptides, one encoded a peptide identical to immunoglobulin G (IgG) heavy-chain constant region. IgG immunostaining was stronger in mesenchymal cells than in cancer cells in the tumors and was apparent in serrated adenoma.Conclusions: The five-phage peptide classifier stands out as promising early diagnostic biomarkers for CRC, but it is unsuitable for discriminating CRC from autoimmune diseases. Truncated IgGs generated from the tumors might be novel CRC-associated antigens. Clin Cancer Res; 17(17); 5715-24. Ó2011 AACR.

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Section: Discussionmentioning

confidence: 49%

Development of Autoantibody Signatures as Biomarkers for Early Detection of Colorectal Carcinoma

Chang

Wu²,

Cao³

et al. 2011

Clinical Cancer Research

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“…Recent case reports suggest that the progression of an SSA to a carcinoma may take as little as 8 months [18]. In a larger cohort, a significant association between large serrated polyps and synchronous advanced adenocarcinomas could also be detected [19].…”

Section: Introductionmentioning

confidence: 89%

Serrated polyps of the colon and rectum (hyperplastic polyps, sessile serrated adenomas, traditional serrated adenomas, and mixed polyps)—proposal for diagnostic criteria

Aust

Baretton

2010

Virchows Arch

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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, represent a heterogeneous group of polyps with characteristic serrated morphology some of which exhibit a significant risk of neoplastic progression. These serrated lesions show characteristic epigenetic alterations not commonly seen in colorectal adenomas and progress to colorectal carcinoma via the so-called serrated pathway (CpG-island-methylation-phenotype pathway). This group of polyps is comprised not only of hyperplastic polyps, but also of sessile serrated adenomas, traditional serrated adenomas and mixed polyps, showing serrated and "classical" adenomatous features. Diagnostic criteria and nomenclature for these lesions are not uniform and, therefore, somewhat confusing. In a consensus conference of the Working Group of Gastroenterological Pathology of the German Society of Pathology, standardization of nomenclature and diagnostic criteria as well as recommendations for clinical management of these serrated polyps were formulated and are presented herein.

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“…22 HPS is associated with an increased CRC risk. 5,7,19,[22][23][24][25][26][27] Previously published case series report CRC at clinical presentation in up to 50% of patients with HPS and interval carcinomas, ie, carcinomas occurring after HPS diagnosis and during endoscopic surveillance, in up to 25% of patients. 24,28 However, because HPS is a heterogeneous condition, comprising serrated polyps of different categories, (ie, HPs and SSAs but also coexistent conventional adenomas 22,23,28 -30 ) it is uncertain which polyps eventually lead to CRC in these patients and, thus, are clinically relevant.…”

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confidence: 99%

A Serrated Colorectal Cancer Pathway Predominates over the Classic WNT Pathway in Patients with Hyperplastic Polyposis Syndrome

Boparai

Dekker

Polak

et al. 2011

The American Journal of Pathology

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Hyperplastic polyposis syndrome (HPS) is character-ized by the presence of multiple colorectal serrated polyps and is associated with an increased colorectal cancer (CRC) risk. The mixture of distinct precursor lesion types and malignancies in HPS provides a unique model to study the canonical pathway and a proposed serrated CRC pathway in humans. To establish which CRC pathways play a role in HPS and to obtain new support for the serrated CRC pathway, we assessed the molecular characteristics of polyps (n ‫؍‬ 84) and CRCs (n ‫؍‬ 19) in 17 patients with HPS versus control groups of various sporadic polyps (n ‫؍‬ 59) and sporadic microsatellite-stable CRCs (n ‫؍‬ 16). In HPS and sporadic polyps, APC mutations were exclusively identified in adenomas, whereas BRAF mutations were confined to serrated polyps. Six of 19 HPS CRCs (32%) were identified in a serrated polyp. Mutation analysis performed in the CRC and the serrated component of these lesions showed identical BRAF mutations. One HPS CRC was located in an adenoma, both components harboring an identical APC mutation. Overall, 10 of 19 HPS CRCs (53%) carried a BRAF mutation versus none in control group CRCs (P ‫؍‬ 0.001). Six BRAF-mutated HPS CRCs (60%) were microsatellite unstable owing to MLH1 methylation. These findings provide novel supporting evidence for the existence of a predominant serrated CRC pathway in HPS, generating microsatellite-stable and microsatellite-instable CRCs.

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Progression of a Sessile Serrated Adenoma to an Early Invasive Cancer Within 8 Months

Cited by 112 publications

References 17 publications

Development of Autoantibody Signatures as Biomarkers for Early Detection of Colorectal Carcinoma

Development of Autoantibody Signatures as Biomarkers for Early Detection of Colorectal Carcinoma

Serrated polyps of the colon and rectum (hyperplastic polyps, sessile serrated adenomas, traditional serrated adenomas, and mixed polyps)—proposal for diagnostic criteria

A Serrated Colorectal Cancer Pathway Predominates over the Classic WNT Pathway in Patients with Hyperplastic Polyposis Syndrome

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