Expression of Cyclin-dependent Kinase Inhibitor p21(WAF1/CIP1) in Non-small Cell Lung Carcinomas: Relationship with p53 Status and Proliferative Activity

Myong, Na Hye

Abstract

PURPOSE: The objectives of this study are to elucidate the level of p21(WAF1/CIP1) expression in non-small cell lung carcinomas (NSCLCs) and to investigate the relationship between the p21(WAF1/CIP1) expression and clinicopathologic features; p53 overexpression; and proliferative activity measured by Ki-67 expression.
MATERIALS AND METHODS
The expressions of p21(WAF1/CIP1), p53, and Ki-67 proteins were analyzed by immunohistochemistry in 45 formalin-fixed and paraffin-embedded NSCLC specimens. 43 patients underwent curative resections and 2 patients had bronchoscopic biopsy specimens only. The correlations between p21(WAF1/CIP1) immunoexpression and p53 status; Ki-67 proliferative activity; and clinicopathologic parameters were analyzed statistically by chi-square or Fisher's exact test.
RESULTS
p21(WAF1/CIP1) expression in the carcinoma cells was found in 28 (62%) of 45 cases. There was no significant correlation between p21(WAF1/CIP1) expression and abnormal accumulation of p53 protein. In 16 (36%) of 45 cases, p21(WAF1/CIP1) was expressed inde pendently of p53 overexpressions. p21WAF1/CIP1 expression was not associated with patient sex, smoking history, pathological stage, tumor size, histological grade or type. However, p21WAF1/CIP1 immunoreactivity was significantly higher in older individuals over 59 years and tended to occur more intensely in the more highly differentiated portion of the squamous carcinoma. Also, a positive correlation between p21WAF1/CIP1 and Ki-67 expression was observed.
CONCLUSIONS
The present findings overall suggest that aberrations in the relationship between p21(WAF1/CIP1) and p53 expressions may be important in the development of NSCLCs; that a p53-independent pathway may be substantially involved in the induction of p21(WAF1/CIP1) expression in NSCLCs; and that the proliferative activity of lung cancers might be dependent on positive control of the cell cycle by p21(WAF1/CIP1).