Nuclear accumulation of p53 correlates significantly with clinical features and inversely with the expression of the cyclin-dependent kinase inhibitor p21(WAF1/CIP1) in pancreatic cancer

Recent studies have suggested a p53 independent expression of p21(WAF1/CIP1). We investigated the correlation between p53 overexpression and the expression of p21(WAF1/CIP1) in 57 patients with pancreatic adenocarcinoma. By means of reverse transcription and polymerase chain reaction (RT-PCR), we examined the mRNA levels of WAF1/CIP1 and compared them with the p53 status in 20 patients and in a further six pancreatic tumour cell lines. In pancreatic cancer tissues, immunohistological evaluation revealed a significant correlation between active p53 and p21(WAF1/CIP1) (P < 0.005) as well as WAF1/CIP1 mRNA expression (P < 0.005). This coherence was also evident in human pancreatic carcinoma cell lines. The analysis of p53 and p21(WAF1/CIP1) expression in relation to clinicopathological features revealed a significant correlation between p53 overexpression and tumour stage, tumour size, grading and lymph node metastases, whereas p21(WAF1/CIP1) expression correlated only with tumour size. We conclude that the expression of p21(WAF1/CIP1) normally depends on active p53, but that there may also exist p53-independent pathways of induction that reduce the correlation of p21(WAF1/CIP1) to clinicopathological features.