Stomach cancer highly expresses both initiator and effector caspases; an immunohistochemical study

Caspases play an essential role during apoptotic cell death. While caspases 8 and 10 act as initiator caspases of the extrinsic apoptosis pathway, caspase 9 acts as an initiator caspase of the intrinsic apoptosis pathway. Caspase 3 is considered to be the main effector caspase involved in both intrinsic and extrinsic pathways. Alteration of apoptosis is essential for cancer development. Thus, analysis of the expression status of caspases, the main executioners of apoptosis, in cancer tissues is needed for a sophisticated understanding of cancer biology. In the current study, we analyzed the expression of caspases 3, 8, 9 and 10 in 60 advanced gastric adenocarcinomas by immunohistochemistry using a tissue microarray approach. Immunopositivity was observed for caspase 3 in 57 (95%), caspase 8 in 56 (93%), caspase 9 in 54 (90%), and caspase 10 in 58 (97%) of the 60 cancers. While 46 cancers (77%) expressed all of the caspases examined, 14 cancers (23%) showed loss of expression in one or more caspases examined. Normal gastric mucosal cells showed no or weak expression of caspases 3, 8, 9 and 10. Taken together, these results suggest that stomach cancer cells in vivo may need caspase expression for apoptosis. Also, higher expression of the caspases in stomach cancer cells than in normal gastric mucosal cells suggests that apoptosis in susceptible stomach cancer cells might be easily triggered, thereby producing selective pressure to make more apoptosis-resistant cells during tumor development.