Distinct profile of HIF1α, PTCH, Eph B2, or DNA repair protein expression and BRAF mutation in colorectal serrated adenoma.

Background and Aims The serrated colorectal carcinoma ( CRC) as proposed to arise from serrated adenoma ( SA) is characterized by upregulation of HIF1α, suppression of PTCH or Eph B2, 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 Eph B2, 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). Results Increase of nuclear HIF1α 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 hMLH1 and MGMT expression were most frequent in SSA ( P < 0.001). Loss of hMSH2 showed more pronounced in SA and HP than AD ( P ≤ 0.004). Methylations of PTCH and Eph B2 were rare in all categories. BRAF mutation harbored frequently in SA, but not AD; only AD harbored Kras mutation. Conclusions This work provides evidence of similarity of HIF1α, Eph B2 or DNA repair proteins expression, and BRAF mutation in serrated CRCs and their precursors, especially SSA, compared with AD and HP. [ABSTRACT FROM AUTHOR]