Correlation between reduced p21^WAF1/CIP1 expression and abnormal p53 expression in esophageal carcinomas

p21^WAF1/CIP1 is a potent inhibitor of various cyclin-dependent kinases, the expression of which is transcriptionally regulated by tumor suppressor gene product p53. We immunohistochemically examined the expression of p53 and p21^WAF1/CIP1in 61 esophageal squamous cell carcinomas. p53 protein was expressed in 37 (61%) of 61 carcinomas. p21^WAF1/CIP1 was consistently expressed in the normal stratified esophageal mucosa. In the carcinomas, the expression of p21^WAF1/CIP1 protein was markedly reduced or not expressed in 33 (54%) cases. Clinicopathologic analyses revealed that no significant correlation exists either between p53-positive and -negative cases or between p21^WAF1/CIP1-positive and -negative cases. Twenty-four cases were p53-positive/ p21^WAF1/CIP1-negative, 15 were p53-negative/p21^WAF1/CIP1-positive, 13 were positive for both and 9 were negative for both, and these findings thus showed an inverse correlation of the positivity between p53 and P21^WAF1/CIP1 (p<0.05). Furthermore, of the 13 cases with positive staining for both, the distribution of the expression was mutually exclusive in 6 cases and coincidental in the remaining 7 cases. These findings showed the p53-dependent expression of p21^WAF1/CIP1 was observed in esophageal squamous cell carcinomas, while the lack of an absolute correlation between abnormal p53 expression and p21^WAF1/CIP1 expression suggested that the p53-independent expression of p21^WAF1/CIP1 might also occur in some portions of the esophageal squamous carcinomas, suggesting that the molecular mechanisms of esophageal carcinogenesis appear to be complicated.