Expression of CDK inhibitor p16(CDKN2/MTS1/INK4A) in human gastric carcinomas

The expression of a cyclin-dependent kinase inhibitor p16(CDKN2/MTS1/INK4A) in adenocarcinoma of the stomach was immunohistochemically examined. The expression of p16 was detected in 81% (47/56) of the adenocarcinomas, among which 29% expressed p16 strongly. The incidence of p16 expression did not differ by histological types of gastric carcinoma. Since p16 acts as a tumor suppressor through inhibition of cell cycle progression, we focused on p16-negative tumors. The p16-negative tumors were frequently found in the cases invading into muscularis propria or the cases of stages 2, 3 and 4 in comparison with that in carcinomas limited to submucosa or the stage 1 cases. The incidence of p16-negative cases was significantly higher in carcinomas with lymph node metastasis (31%) than those without metastasis (10%). There was no apparent correlation between the p16 expression and the expression of p53, Ki-67, p21, and cyclin E. These findings suggest that loss of p16 expression might be associated with the progression of gastric cancer.