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Distinct profile of HIF 1α, PTCH , E ph B 2, or DNA repair protein expression and BRAF mutation in colorectal serrated adenoma
Author(s) -
Morimoto Takashi,
Mitomi Hiroyuki,
Saito Tsuyoshi,
Takahashi Michiko,
Murakami Takashi,
Sakamoto Naoto,
Yao Takashi,
Watanabe Sumio
Publication year - 2014
Publication title -
journal of gastroenterology and hepatology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.214
H-Index - 130
eISSN - 1440-1746
pISSN - 0815-9319
DOI - 10.1111/jgh.12553
Subject(s) - mutation , microbiology and biotechnology , cancer research , downregulation and upregulation , medicine , biology , gene , genetics
Background and Aims The serrated colorectal carcinoma ( CRC ) as proposed to arise from serrated adenoma ( SA ) is characterized by upregulation of HIF 1α, suppression of PTCH or E ph B 2, loss of DNA repair proteins, and BRAF mutation. The aim of this study was to evaluate alterations of these candidates involved in the serrated pathway in colorectal polyps. Methods We analyzed immunoreactivity of these proteins, methylation of PTCH and E ph B 2, and mutation of BRAF and K ras in sessile SAs ( SSAs ; n = 32), traditional SA s ( n = 28), hyperplastic polyps ( HP s; n = 24), and conventional adenomas ( AD s; n = 21). Results Increase of nuclear HIF 1α expression was more frequent in SA than HP , but less frequent in SA than AD ( P < 0.001). Increase of PTCH expression was not found in SSA or HP , but was evident in about half of traditional SA and all AD ( P < 0.001). Decrease of EphB2 expression was more prominent in SA than HP or AD ( P ≤ 0.005). Loss of hMLH 1 and MGMT expression were most frequent in SSA ( P < 0.001). Loss of hMSH 2 showed more pronounced in SA and HP than AD ( P ≤ 0.004). Methylations of PTCH and E ph B 2 were rare in all categories. BRAF mutation harbored frequently in SA , but not AD ; only AD harbored K ras mutation. Conclusions This work provides evidence of similarity of HIF 1α, E ph B 2 or DNA repair proteins expression, and BRAF mutation in serrated CRCs and their precursors, especially SSA , compared with AD and HP .