Immunohistochemical and genetic characteristics of a colorectal mucin‐rich variant of traditional serrated adenoma

• Published in: Histopathology 2018-09, Vol.73 (3), p.444-453
• Main Authors: Hiromoto, Takafumi, Murakami, Takashi, Akazawa, Yoichi, Sasahara, Noriko, Saito, Tsuyoshi, Sakamoto, Naoto, Mitomi, Hiroyuki, Nagahara, Akihito, Yao, Takashi
• Format: Article
• Language: English
• Subjects: Adenoma; Adenoma - genetics; Adenoma - pathology; Adult; Aged; Aged, 80 and over; Biomarkers, Tumor - analysis; BRAF; Catenin; Colorectal carcinoma; Colorectal Neoplasms - genetics; Colorectal Neoplasms - pathology; Female; Humans; Immunohistochemistry; KRAS; Male; Middle Aged; MLH1 protein; Morphology; Mucin; Mucins; mucin‐rich variant; Mutation; Proto-Oncogene Proteins B-raf - genetics; serrated tubulovillous adenoma; traditional serrated adenoma; Tumors
• ISSN: 0309-0167; 1365-2559
• DOI: 10.1111/his.13643

Aims Recently, several morphological variants of traditional serrated adenoma (TSA) of the colorectum have been recognised, and mucin‐rich TSA (MR‐TSA) and serrated tubulovillous adenoma (S‐TVA) were introduced as distinct morphological variants separate from conventional TSA (C‐TSA). This aim of this study was to elucidate the immunohistochemical and genetic characteristics of MR‐TSAs. Methods and results We performed immunostaining for cytokeratins (CKs) (e.g. CK7 and CK20), mucins (e.g. MUC2, MUC5AC, MUC6, and CD10), β‐catenin, and MLH1, and direct sequencing of BRAF/KRAS, in 32 MR‐TSAs, 35 C‐TSAs, and 23 S‐TVAs. Immunohistochemically, all studied cases were positive for CK20, whereas few cases were positive for CK7, with no significant differences between the three groups. Regarding mucin‐phenotypic expression, all cases were positive for MUC2 but negative for MUC6 and CD10. MUC5AC positivity was found significantly more frequently in MR‐TSAs (53%) than in C‐TSAs (26%; P = 0.026). Nuclear β‐catenin expression in MR‐TSAs was significantly less frequent than in S‐TVAs (P = 0.002). MLH1 nuclear staining was retained in all cases. Genetically, MR‐TSAs (75%) more frequently harboured BRAF mutation than C‐TSAs (49%; P = 0.044) or S‐TVAs (4%; P < 0.001), whereas only two cases (6%) of MR‐TSA harboured a KRAS mutation, a frequency that was significantly lower than that in C‐TSAs (26%; P = 0.047) or S‐TVAs (57%; P < 0.001). Conclusions MR‐TSAs more frequently harboured BRAF mutations than C‐TSAs, and had distinct immunohistochemical characteristics. Our findings indicated that MR‐TSAs could be important precursors of BRAF‐mutated, microsatellite‐stable subtypes of colorectal carcinoma.