EXPRESSION OF P21(WAF1 CIP1), SOFT-TISSUE SARCOMAS - A COMPARATIVE IMMUNOHISTOCHEMICAL STUDY WITH P53 AND KI-67/

The p53 gene controls the cell cycle by transactivating p21(WAF1/CIP1) , a cyclin dependent kinase (cdk) inhibitor. By inhibiting cdks, p21(W AF1/CIP1) regulates the cell cycle by blocking the G1 to S phase trans ition. In this study, we analyzed the immunohistochemical expression o f p21(WAF1/CIP1) in 66 soft tissue sarcomas and its relationship to p5 3 and the cell cycle proliferation antigen Ki-67. Expression of p21(WA F1/CIP1) was detected in 76% of the tumors and p53 in 26%. All maligna nt schwannomas, synovial sarcomas, leiomyosarcomas and gastrointestina l stromal tumors expressed p21(WAF1/CIP1). The majority of angiosarcom as, dermatofibrosarcomas, and fibrosarcomas showed low expression or w ere negative for p21(WAF1/CIP1). Ewing's sarcomas, liposarcomas, and m alignant fibrous histiocytomas were heterogeneous in their expression of p21(WAF1/CIP1). Combining p53 and p21(WAF1/CIP1) staining, the foll owing four patterns were observed: 23% of the tumors showed the p53+/p 21+ pattern; 53% showed the p53-/p21+ pattern; 3% showed the p53(+)/p2 1- pattern and 21% were negative for both p53 and p21(WAF1/CTP1). Ther e was no correlation between Ki-67 and p21(WAF1/CIP1) or p53 staining. Our results show that soft tissue sarcomas, independent of their hist ologic subtype, frequently express p21(WAF1/CIP1) which is probably im portant in their tumorigenesis. Additionally, p21(WAF1/CIP1) may play a role in determining the efficacy of various cell cycle-directed ther apies in soft tissue sarcomas.