Clinicopathological features and phenotypic classification of de novo-type colorectal carcinomas differ from those of colorectal carcinomas derived from flat adenomas

Since adenoma components disappear with tumor progression, it is not known whether colorectal carcinomas (CRCs) are derived from an adenoma-carcinoma sequence or are de novo. We compared 38 cases of <= 10-mm flat CRCs without an adenoma component (de novo type) with 39 cases of <= 10-mm flat CRCs with an adenoma component (carcinoma in adenoma (CIA) type). Compared to the CIA type, the de novo-type CRCs were more frequently located in the proximal colon; more frequently invaded submucosa, and more frequently had venous permeation. Regarding the phenotypic classification based on the immunohistochemical expressions of CD10, MUC2 and MUC5AC, the incidence of unclassified type (CD10-, MUC2- and MUC5AC-) was significantly more frequent in the de novo (32%) than CIA (5%) type. In one de novo-type case, mismatch repair (MMR) protein loss was judged, because MLH1 and PMS2 protein expressions were immunohistochemically negative. BRAF mutation (V600E) was seen in one de novo-type case and two CIA-type cases, but none of these cases had MMR protein loss. In conclusion, small-intestinal type (CD10+ and MUC5AC-) is the most common in flat CRC and unclassified type is mainly characteristic of de novo type. In this study, small flat CRCs with BRAF mutation do not have MMR protein loss.