Immunohistochemical analysis of cell death pathways in gastrointestinal adenocarcinoma.

Caspase-8 and caspase-9 play crucial roles in the extrinsic and intrinsic apoptotic pathways, respectively. The nuclear translocation of apoptosis-inducing factor (AIF) is involved in caspase-independent apoptosis. Microtubule-associated protein 1 light chain 3 (LC3) plays a pivotal role in autophagy. In the present study, we analyzed the expression of cleaved caspase-8 (CC8), cleaved caspase-9 (CC9), AIF, and LC3 in 160 gastrointestinal adenocarcinomas. The nuclear expression of AIF was rare. The expression of CC8 in gastric and colorectal adenocarcinomas did not differ, whereas the percentage of CC9-positive tumors in gastric adenocarcinomas was significantly higher than in colorectal adenocarcinomas. In contrast, the percentage of LC3-positive tumors in gastric adenocarcinomas was significantly lower than in colorectal adenocarcinomas. CC8 and CC9 occasionally co-existed in the same tumor cells in gastric adenocarcinoma. However, LC3-positive tumor cells in colorectal adenocarcinomas were constantly negative for CC8. No correlation was identified between the expression of any markers and clinicopathological parameters. These results suggest that different cell death pathways are activated in a manner that depends upon the primary site and cell type. The extrinsic and intrinsic apoptotic pathways may be mutually regulated in gastric adenocarcinomas. Also, autophagy may function as a cellular guardian to avoid apoptosis in colorectal adenocarcinomas.