Low level of p27(Kip1) protein expression in gastric adenocarcinoma is associated with disease progression and poor outcome

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Abstract
Background and Objectives Low tumor expression of the p27Kip1 protein, which is involved in cell cycle control and apoptosis, is considered a negative prognostic factor in different types of cancer. The aim of this study was to evaluate the clinical and pathological significance of low p27Kip1 protein expression in patients who had undergone resection for gastric adenocarcinoma. Methods p27Kip1 protein was studied by immunohistochemistry in formalin‐fixed tumor sections from 95 patients who underwent resection for gastric adenocarcinoma between 1991 and 1996. Based on the median value of protein expression, p27Kip1 protein expression was classified as low or high. Results Low p27Kip1 protein expression was significantly associated with tumor de‐differentiation, increased penetration through the gastric wall, lymph node metastasis, and advanced tumor stage. In the group of 84 patients who underwent curative surgery, 5‐year survival was 74% in cases with high p27Kip1 protein expression and 38% in those with low p27Kip1 protein expression (P < 0.001). At multivariate analysis, low p27Kip1 protein expression was an independent negative prognostic factor for survival (RR = 3.671; P = 0.004). Conclusions In gastric adenocarcinoma, low p27Kip1 protein expression is associated with poorly differentiated and advanced tumors and is a negative prognostic factor of potential clinical value. J. Surg. Oncol. 2002;81:167–176. © 2002 Wiley‐Liss. Inc.