Expression of doublecortin and CaM kinase-like-1 protein in serrated neoplasia of the colorectum.

The adenoma-carcinoma sequence (ACS) and the serrated pathway are two distinct developmental routes leading to the formation of colorectal carcinoma. Recently, the doublecortin and CaM kinase-like-1 protein (DCLK1) has been reported to serve as an intestinal cancer stem cell marker and has been demonstrated to be overexpressed through the ACS; however, there is a lack of reports on the role of DCLK1 in the serrated pathway. To clarify the correlation between DCLK1 protein expression and clinicopathological characteristics of the serrated tumorigenic pathway, the present study used immunohistochemistry to examine the expression of DCLK1 in endoscopically resected samples of 62 serrated polyps [20 hyperplastic polyps (HPs), 16 traditional serrated adenomas (TSAs) and 26 sessile serrated adenoma-polyps (SSA/Ps)], as well as 20 non-serrated adenomas, 20 carcinoma in adenomas (CIAs) and 18 early pure colorectal carcinomas without any adenoma component (EPCs). Based on immunostaining score, high DCLK1 expression was detected in 20.0% of HPs (23.1% of microvesicular HPs and 14.3% of goblet cell HPs), 37.5% of TSAs, 7.7% of SSA/Ps, 80.0% of non-serrated adenomas, 75.0% of CIAs and 50.0% of EPCs. Negative or low DCLK1 expression was frequently observed in TSAs (P<0.005), SSA/Ps (P<0.00001) and EPCs (P<0.04) compared with non-serrated adenomas and CIAs. In addition, negative or low DCLK1 expression was significantly more frequent in SSA/Ps (92.3%) compared with TSAs (62.5%; P<0.05). Thus, the expression pattern of DCLK1 between the serrated pathway and ACS differed, indicating that DCLK1 expression may perform a secondary role in serrated tumorigenesis. In addition, the data indicates that EPCs may contain tumors derived from the serrated pathway as well as the ACS.