{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,10,21]],"date-time":"2025-10-21T15:29:59Z","timestamp":1761060599343,"version":"3.37.3"},"reference-count":32,"publisher":"Wiley","issue":"4","license":[{"start":{"date-parts":[[2018,8,2]],"date-time":"2018-08-02T00:00:00Z","timestamp":1533168000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"DOI":"10.13039\/501100001691","name":"japan society for the promotion of science","doi-asserted-by":"publisher","award":["17K08711"],"award-info":[{"award-number":["17K08711"]}],"id":[{"id":"10.13039\/501100001691","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Histopathology"],"published-print":{"date-parts":[[2018,10]]},"abstract":"Aims<\/jats:title>Sessile serrated adenoma\/polyp (SSA<\/jats:styled-content>\/P) is regarded as a genetically homogeneous entity, with most lesions harbouring the BRAF<\/jats:styled-content><\/jats:italic> V600E mutation. The present study aimed to reappraise the genetic heterogeneity of SSA<\/jats:styled-content>\/Ps and its clinicopathological significance.<\/jats:p><\/jats:sec>Methods and results<\/jats:title>We performed next\u2010generation sequencing of 272 SSA<\/jats:styled-content>\/Ps without dysplasia and evaluated morphological and molecular features associated with the respective genotypes. BRAF<\/jats:styled-content><\/jats:italic> V600E, BRAF<\/jats:styled-content><\/jats:italic> non\u2010V600E, KRAS<\/jats:styled-content><\/jats:italic> and NRAS<\/jats:styled-content><\/jats:italic> mutations were found in 223 (82.0%), three (1.2%), 28 (10.3%) and one lesion (0.4%), respectively. Notably, all lesions with BRAF<\/jats:styled-content><\/jats:italic> non\u2010V600E mutations had either KRAS<\/jats:styled-content><\/jats:italic> or NRAS<\/jats:styled-content><\/jats:italic> mutations concurrently. Twenty SSA<\/jats:styled-content>\/Ps (7.4%) were negative for these mutations. KRAS<\/jats:styled-content><\/jats:italic>\u2010mutated SSA<\/jats:styled-content>\/Ps were located more often in the distal colon (42%) compared to those with the BRAF<\/jats:styled-content><\/jats:italic> V600E mutation (14%). Histologically, minimally serrated crypts and goblet cell\u2010rich crypts were more common in KRAS<\/jats:styled-content><\/jats:italic>\u2010mutated and mutation\u2010negative SSA<\/jats:styled-content>\/Ps. However, in most instances, SSA<\/jats:styled-content>\/Ps lacking the BRAF<\/jats:styled-content><\/jats:italic> V600E mutation were indistinguishable morphologically from those with the BRAF<\/jats:styled-content><\/jats:italic> V600E mutation. MUC<\/jats:styled-content>5AC<\/jats:styled-content> and MUC<\/jats:styled-content>6 expression was common regardless of the mutation status, but more extensive in SSA<\/jats:styled-content>\/Ps with the BRAF<\/jats:styled-content><\/jats:italic> V600E mutation. CpG island methylator phenotype\u2010high was more frequent in SSA<\/jats:styled-content>\/Ps with the BRAF<\/jats:styled-content><\/jats:italic> V600E mutation (60%), followed by mutation\u2010negative SSA<\/jats:styled-content>\/Ps (40%) and KRAS<\/jats:styled-content><\/jats:italic>\u2010mutated SSA<\/jats:styled-content>\/Ps (16%).<\/jats:p><\/jats:sec>Conclusions<\/jats:title>The present study confirmed the common presence of the BRAF<\/jats:styled-content><\/jats:italic> V600E mutation in SSA<\/jats:styled-content>\/Ps, but also demonstrated a degree of molecular heterogeneity of SSA<\/jats:styled-content>\/Ps. SSA<\/jats:styled-content>\/Ps with and without the BRAF<\/jats:styled-content><\/jats:italic> V600E mutation showed slightly different but overlapping histological and molecular features.<\/jats:p><\/jats:sec>","DOI":"10.1111\/his.13688","type":"journal-article","created":{"date-parts":[[2018,6,19]],"date-time":"2018-06-19T17:45:41Z","timestamp":1529430341000},"page":"672-680","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":11,"title":["Reappraisal of the genetic heterogeneity of sessile serrated adenoma\/polyp"],"prefix":"10.1111","volume":"73","author":[{"given":"Hourin","family":"Cho","sequence":"first","affiliation":[{"name":"Division of Pathology and Clinical Laboratories National Cancer Center Hospital Tokyo Japan"},{"name":"Endoscopy Division National Cancer Center Hospital Tokyo 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