THE CLINICAL-SIGNIFICANCE OF P21(WAF1 CIP-1) AND P53 EXPRESSION IN PANCREATIC ADENOCARCINOMA/

BACKGROUND. Wild-type p53 protein activates the WAF1/CIP-1 (p21) gene, leading to G1 arrest after DNA damage. The authors investigated the r elation of p21 and p53 expression in pancreatic adenocarcinomas to dis ease stage, overall patient survival, and survival when chemotherapy o r radiation therapy was given. METHODS. Paraffin embedded tissue secti ons of 75 ductal adenocarcinomas of the pancreas were immunostained fo r p53 and p21. Nuclear expression was scored as absent, focal (<10%), moderate (10-50%), or strong or diffuse (>50%). RESULTS. The median su rvival of patients whose pancreatic tumors expressed the p21 protein ( 43 of 75 cases, 57%) was better than that for patients whose tumors we re p21 negative (32 of 75 cases, 43%) (median survival, 13,5 vs. 9.8 m onths, respectively; P = 0.23). No difference in survival was found wi th regard to p53 protein expression (43 of 75 cases, 57%); however, st rong p53 expression was significantly associated with advanced disease stage (70% in Stage IV vs. 13-28% in lower stages). Expression of p21 correlated with earlier clinical stage. Stage specific comparisons sh owed a trend toward increased survival among p21 positive tumor patien ts diagnosed at clinical Stages I and III but not among those diagnose d at Stage IV, Adjuvant chemotherapy or radiation improved survival si gnificantly if tumors expressed p21 or no p53. CONCLUSIONS. Expression of p21 is significantly associated with earlier clinical stage in pan creatic adenocarcinoma, perhaps accounting far the better survival obs erved in this patient group than among those whose tumors were p21 neg ative. Improved survival with either chemotherapy or radiation therapy was observed for patients whose tumors were p21 positive or p53 negat ive. (C) 1997 American Cancer Society.