Distinct profile of HIF1a, PTCH, EphB2, or DNA repair protein expression and BRAF mutation in colorectal serrated adenoma

作者：Morimoto Takashi; Mitomi Hiroyuki^*; Saito Tsuyoshi; Takahashi Michiko; Murakami Takashi; Sakamoto Naoto; Yao Takashi; Watanabe Sumio

来源：Journal of Gastroenterology and Hepatology, 2014, 29(6): 1192-1199.

DOI：10.1111/jgh.12553

• BRAF
• EphB2
• HIF1
• PTCH
• serrated adenoma

Background and AimsThe serrated colorectal carcinoma (CRC) as proposed to arise from serrated adenoma (SA) is characterized by upregulation of HIF1, suppression of PTCH or EphB2, 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. %26lt;br%26gt;MethodsWe analyzed immunoreactivity of these proteins, methylation of PTCH and EphB2, and mutation of BRAF and Kras in sessile SAs (SSAs; n=32), traditional SAs (n=28), hyperplastic polyps (HPs; n=24), and conventional adenomas (ADs; n=21). %26lt;br%26gt;ResultsIncrease of nuclear HIF1 expression was more frequent in SA than HP, but less frequent in SA than AD (P%26lt;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%26lt;0.001). Decrease of EphB2 expression was more prominent in SA than HP or AD (P0.005). Loss of hMLH1 and MGMT expression were most frequent in SSA (P%26lt;0.001). Loss of hMSH2 showed more pronounced in SA and HP than AD (P0.004). Methylations of PTCH and EphB2 were rare in all categories. BRAF mutation harbored frequently in SA, but not AD; only AD harbored Kras mutation. %26lt;br%26gt;ConclusionsThis work provides evidence of similarity of HIF1, EphB2 or DNA repair proteins expression, and BRAF mutation in serrated CRCs and their precursors, especially SSA, compared with AD and HP.

• 出版日期2014-6