Expression of p21(WAF1/CIP1) in 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(WAF1/CIP1) regulates the cell cycle by blocking the G1 to S phase transition. In this study, we analyzed the immunohistochemical expression of p21(WAF1/CIP1) in 66 soft tissue sarcomas and its relationship to p53 and the cell cycle proliferation antigen Ki-67. Expression of p(21WAF1/CIP1) was detected in 76% of the tumors and p53 in 26%. All malignant schwannomas, synovial sarcomas, leiomyosarcomas and gastrointestinal stromal tumors expressed p21(WAF1/CIP1). The majority of angiosarcomas, dermatofibrosarcomas, and fibrosarcomas showed low expression or were negative for p21(WAF1/CIP1). Ewing's sarcomas, liposarcomas, and malignant fibrous histiocytomas were heterogeneous in their expression of p21(WAF1/CIP1). Combining p53 and p21(WAF1/CIP1) staining, the following four patterns were observed: 23% of the tumors showed the p53+/p21+ pattern; 53% showed the p53-/p21+ pattern; 3% showed the p53⁺/p21- pattern and 21% were negative for both p53 and p21(WAF1/CIP1). There was no correlation between Ki-67 and p21(WAF1/CIP1) or p53 staining. Our results show that soft tissue sarcomas, independent of their histologic subtype, frequently express p21(WAF1/CIP1) which is probably important in their tumorigenesis. Additionally, p21(WAF1/CIP1) may play a role in determining the efficacy of various cell cycle-directed therapies in soft tissue sarcomas.