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Reappraisal of the genetic heterogeneity of sessile serrated adenoma/polyp
Author(s) -
Cho Hourin,
Hashimoto Taiki,
Yoshida Hiroshi,
Taniguchi Hirokazu,
Ogawa Reiko,
Mori Taisuke,
Hiraoka Nobuyoshi,
Saito Yutaka,
Sekine Shigeki
Publication year - 2018
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.13688
Subject(s) - kras , v600e , neuroblastoma ras viral oncogene homolog , mutation , biology , cancer research , genetic heterogeneity , genetics , phenotype , gene
Aims Sessile serrated adenoma/polyp ( SSA /P) is regarded as a genetically homogeneous entity, with most lesions harbouring the BRAF V600E mutation. The present study aimed to reappraise the genetic heterogeneity of SSA /Ps and its clinicopathological significance. Methods and results We performed next‐generation sequencing of 272 SSA /Ps without dysplasia and evaluated morphological and molecular features associated with the respective genotypes. BRAF V600E, BRAF non‐V600E, KRAS and NRAS mutations were found in 223 (82.0%), three (1.2%), 28 (10.3%) and one lesion (0.4%), respectively. Notably, all lesions with BRAF non‐V600E mutations had either KRAS or NRAS mutations concurrently. Twenty SSA /Ps (7.4%) were negative for these mutations. KRAS ‐mutated SSA /Ps were located more often in the distal colon (42%) compared to those with the BRAF V600E mutation (14%). Histologically, minimally serrated crypts and goblet cell‐rich crypts were more common in KRAS ‐mutated and mutation‐negative SSA /Ps. However, in most instances, SSA /Ps lacking the BRAF V600E mutation were indistinguishable morphologically from those with the BRAF V600E mutation. MUC 5 AC and MUC 6 expression was common regardless of the mutation status, but more extensive in SSA /Ps with the BRAF V600E mutation. CpG island methylator phenotype‐high was more frequent in SSA /Ps with the BRAF V600E mutation (60%), followed by mutation‐negative SSA /Ps (40%) and KRAS ‐mutated SSA /Ps (16%). Conclusions The present study confirmed the common presence of the BRAF V600E mutation in SSA /Ps, but also demonstrated a degree of molecular heterogeneity of SSA /Ps. SSA /Ps with and without the BRAF V600E mutation showed slightly different but overlapping histological and molecular features.