Pathological and biomolecular analyses of colorectal endocrine carcinoma.

Colorectal endocrine carcinomas are a heterogeneous group of tumors that display aggressive clinical behavior and have a poorer prognosis compared with common colorectal adenocarcinomas. On the other hand, poorly differentiated (PD) colorectal carcinomas (CRCs) can rapidly metastasize to distant organs and have a poorer prognosis than do well-differentiated or moderately differentiated CRCs. In 2001, Grabowski et al. reported that neuroendocrine (NE) cell differentiation can be used as an independent prognostic factor in stage III and stage IV CRCs. PDCRCs often show NE cell differentiation in some parts of the tumor and are found more frequently than well-differentiated or moderately differentiated CRCs. Recent research shows that many types of cancer contain their own stem cells, that is cancer stem cells have self-renewing capacity and differentiation ability. It is thought that gastrointestinal cancer stem cells can differentiate into epithelial cells or endocrine cells. However, the mechanism underlying the aggressiveness of endocrine carcinomas and the role of NE cell differentiation in CRC remain unclear. The aims of this study were to investigate the expression of NE cell differentiation in PDCRC tissue and to examine the clinicopathological significance of the expression and its biological metastatic mechanisms. Furthermore, we focused on the anticancer activity of STI571 (i.e., the c-kit tyrosine kinase inhibitor that exhibits substantial therapeutic activity in patients with chronic myeloid leukemia and gastrointestinal stromal tumors associated with the constitutive activation of the BCR-ABL and c-kit tyrosine kinases, respectively) in human colorectal endocrine carcinoma cells in vitro.