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Serrated tubulovillous adenoma of the large intestine
Author(s) -
Bettington Mark,
Walker Neal,
Rosty Christophe,
Brown Ian,
Clouston Andrew,
McKeone Diane,
Pearson SallyAnn,
Klein Kerenaftali,
Leggett Barbara,
Whitehall Vicki
Publication year - 2016
Publication title -
histopathology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.626
H-Index - 124
eISSN - 1365-2559
pISSN - 0309-0167
DOI - 10.1111/his.12788
Subject(s) - kras , mlh1 , hyperplastic polyp , microsatellite instability , methylation , cpg site , biology , pathology , dna methylation , cancer research , colorectal cancer , medicine , cancer , genetics , dna mismatch repair , colonoscopy , microsatellite , gene , allele , gene expression
Aims Most colorectal polyps are classified readily, but a subset of tubulovillous adenomas (TVA) with prominent serrated architecture causes diagnostic confusion. We aimed to (i) identify histological features that separate serrated TVAs from both conventional TVAs and traditional serrated adenomas (TSA) and (ii) perform a clinicopathological and molecular analysis to determine if the serrated TVA has unique features. Methods and results We collected 48 serrated TVAs, 50 conventional TVAs and 66 BRAF wild‐type TSAs for analysis. For each polyp we performed a clinicopathological assessment, BRAF and KRAS mutation profiling, cytosine–phosphate–guanosine (CpG) island methylator phenotype status, MGMT methylation and immunohistochemical assessment of seven markers [MutL homologue 1 (MLH1), p16, p53, β‐catenin, Ki67, CK7 and CK20]. We found that serrated TVAs can be diagnosed reliably, and have features distinct from both conventional TVAs and TSAs. Compared to conventional TVAs, serrated TVAs are larger, more often proximal, more histologically advanced, show more CpG island methylation and more frequent KRAS mutation. Compared to TSAs they are more often proximal, show less CpG island methylation, more frequent MGMT methylation and more frequent nuclear staining for β‐catenin. Conclusions The serrated TVA can be diagnosed reliably and has unique features. It represents a precursor of KRAS mutated, microsatellite stable colorectal carcinoma.