Expression of cell-cycle regulators, cyclin E and p21WAF1/CIP1 potential prognostic markers for gastric cancer

Aims: The deregulation of cyclin, cyclin-dependent kinases (CDKs) and their inhibitors could have a crucial role in the development of diverse human cancers. Methods: In this study, we analysed the expression of cyclin D1, cyclin E, p21(WAF1/CIP1) and p27(KIP1) in 84 surgically resected gastric cancers by immunohistochemistry with long-term follow-up (median 38 months). We also evaluated the relation between each cell cycle regulator and various clinicopathological findings, including age, sex, histological grade, tumour location, tumour type and stage and lymph-node metastasis. Results: Overexpression of cyclin D1 and E was detected in 21/84 (25%) and 34/84 (40.5%) patients, respectively. Normal gastric epithelium showed consistently positive immunostain for p21(WAF1/CIP1) and p27(KIP1) in more than 50% of nuclei. Loss of p21(WAF1/CIP1) and p27(KIP1) expression was noted in 45/84 (53.6%) and 44/54 (52.4%) patients, respectively. Among the various clinicopathological findings, overexpression of cyclin E was associated with lymphnode metastasis (P=0.003) and recurrence (P=0.043). Loss of p21(WAF1/CIP1) expression was more frequent in diffuse type cancers (P=0.005) and was correlated with recurrence (P=0.002) and death (P=0.002). Overexpression of cyclin E and loss of p21(WAF1/CIP1) expression were significantly correlated with decreased disease-free (P=0.037; P= 0.001) and overall(P=0.031; P=0.001) survival. Conclusions: These results suggest that immunohistochemical analysis for cell cycle regulators, especially cyclin E and p21(WAF1/CIP1). might be a useful prognostic indicator in gastric cancer.