Loss of p27Kip1 expression is a strong independent prognostic factor of reduced survival in NO gastric carcinomas

BACKGROUND. p27(Kip1) is a cyclin-dependent kinase inhibitor and is a potential tumor suppressor gene. Reduced expression of p27(Kip1) is a powerful negative prognostic marker in primary lung, breast, colon, bladder, and prostate carcinomas. In the current study, the prognostic value of p27(Kip1) in gastric cancer was evaluated and compared with other histopathologic parameters and p53 expression. METHODS. p27(Kip1) and p53 protein expression were determined by immunohistochemistry in 96 gastric carcinomas. The tumors were from a low incidence population and were selected for the absence of lymph node involvement. RESULTS. Reduced expression of p27(Kip1) (less than or equal to 50% positive cells) and nuclear p53 accumulation (> 30% positive cells) were observed in 67 (69.8%) and 9 (9%) tumors, respectively, and were not related to either the pT category or tumor histology. Kaplan-Meier analyses revealed a significant impact on survival by p27(Kip1) (P = 0.0001 by log rank test), p53 (P < 0.0001) expression, and the pT category (P < 0.0001). On multivariate analysis, reduced p27(Kip1) protein expression was the strongest independent predictor of reduced survival (P = 0.005; relative risk = 3.348) out weighing the pT category (P = 0.010; relative risk = 2.257) and p53 overexpression (P = 0.016; relative risk = 2.618). CONCLUSIONS. These data indicated that immunohistochemical detection of p27(Kip1) could help to identify gastric carcinoma patients who are at high risk of death, even in the absence of lymph node involvement, and who might benefit from an adjuvant treatment following surgery. Cancer 2000;89:2247-57. (C) 2000 American Cancer Society.