Loss of p27(Kip1) 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 poten tial tumor suppressor gene. Reduced expression of p27(Kip1) is a powerful n egative prognostic marker in primary lung, breast, colon, bladder, and pros tate carcinomas. In the current study, the prognostic value of p27(Kip1) in gastric cancer was evaluated and compared with other histopathologic param eters and p53 expression. METHODS. p27(Kip1) and p53 protein expression were determined by immunohist ochemistry in 96 gastric carcinomas. The tumors were from a low incidence p opulation and were selected for the absence of lymph node involvement. RESULTS. Reduced expression of p27(Kip1) (less than or equal to 50% positiv e cells) and nuclear p53 accumulation (> 30% positive cells) were observed in 67 (69.8%) and 9 (9%) tumors, respectively, and were not related to eith er the pT category or tumor histology. Kaplan-Meier analyses revealed a sig nificant 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 independe nt predictor of reduced survival (P = 0.005; relative risk = 3.348) out wei ghing the pT category (P = 0.010; relative risk = 2.257) and p53 overexpres sion (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 ri sk of death, even in the absence of lymph node involvement, and who might b enefit from an adjuvant treatment following surgery. Cancer 2000;89:2247-57 . (C) 2000 American Cancer Society.