Stomach Cancer and Apoptosis: A Review

Abstract

Apoptosis is a distinct form of cell death, distinguishable from necrosis. It is a natural, active process by which cells are eliminated from normal or neoplastic tissue. We describe apoptotic cells in human gastric mucosa, adenomas, and carcinomas with special reference to the role of the p53 gene. Apoptosis plays a role in the morphogenesis of gastritis mucosa, including intestinal metaplasia to eliminate unnecessary or possibly DNA-damaged cells. The frequent occurrence of apoptosis in gastric adenomas may reflect their rather static nature. Apoptosis correlates with proliferative activity and tumorigenesis of gastric carcinoma, in which the apoptotic index (AI) correlates with the histologic type and depth of invasion. Gastric carcinoma with lymphoid stroma (GCLS) demonstrated the lowest AI among the histologic types. This fact might partly correlate with their favorable postoperative prognosis of GCLS compared with ordinary gastric carcinomas. Although the mutated p53 gene attenuates apoptotic cell death, apoptosis of gastric cancer cells occurs in a cell cycle-dependent and a cell cycle-independent manner in vivo. Anticancer agents, transforming growth factor beta, and antiFas antibody variably induce apoptosis in the various human gastric cancer cell lines. In fact, preoperative administration of 5-fluorouracil significantly increased the number of apoptotic cancer cells. Thus apoptosis plays a crucial role in the tumorigenesis and progression of human gastric carcinoma. Selective induction of apoptosis of cancer cells is undoubtedly the best way to treat gastric cancer patients. Further studies should be conducted to clarify variable pathways of signal transduction, which might show a diverse spectrum of biologic effects depending on the apoptosis-inducible agents.