p21(WAF1) expression is associated with improved survival after adjuvant chemoradiation for pancreatic cancer

Background. Cell cycle arrest after DNA damage is partly mediated through t he transcriptional activation of p21(WAF1) by the p53 tumor suppressor gene , p21(WAF1) and P53 are both critical in maintaining cell cycle control in response to DNA damage from radiation or chemotherapy. Therefore, we examin ed the role of p21(WAF1) and p53 in the determination of outcome for patien ts who receive radiation and/or chemotherapy for pancreatic cancer. Methods, p21(WAF1) and p53 protein expression were determined (with the use of immunohistochemistry) in specimens from 90 patients with pancreatic can cer Forty-four patients underwent surgical resection, and 46 patients had e ither locally unresectable tumors (n = 9 patients) or distant metastases (n = 37 patients). Seventy-three percent of the patients who underwent resect ion and 63% of the patients who did not undergo resection received radiatio n and/or chemotherapy. Results. p21(WAF1) expression was present in 48 of 86 tumors (56%) and was significantly (P <.05) associated with advanced tumor stage. Median surviva l among patients with resected pancreatic cancer who received adjuvant chem oradiation with p21(WAF1)-positive tumors was significantly longer than in patients with no p22(WAF1) staining (25 vs 11 months; P =.01). Fifty of 89 tumors (56%) stained positive for p53 protein. p53 overexpression was assoc iated with decreased survival in patients who did not undergo resection. Conclusions. Normal p21(WAF1) expression may be necessary for a beneficial response to current adjuvant chemoradiation protocols for pancreatic cancer Alternate strategies for adjuvant therapy should be explored for patients with pancreatic cancer who lack functional p21(WAF1).