Expression of p21WAF1/CIP1 in soft tissue sarcomas: a comparative immunohistochemical study with p53 and Ki-67.
The p53 gene controls the cell cycle by transactivating p21WAF1/CIP1, a cyclin dependent kinase (cdk) inhibitor. By inhibiting cdks, p21WAF1/CIP1 regulates the cell cycle by blocking the G1 to S phase transition. In this study, we analyzed the immunohistochemical expression of p21WAF1/CIP1 in 66 soft tissue sarcomas and its relationship to p53 and the cell cycle proliferation antigen Ki-67. Expression of p21WAF1/CIP1, was detected in 76% of the tumors and p53 in 26%. All malignant schwannomas, synovial sarcomas, leiomyosarcomas and gastrointestinal stromal tumors expressed p21WAF1/CIP1. The majority of angiosarcomas, dermatofibrosarcomas, and fibrosarcomas showed low expression or were negative for p21WAF1/CIP1. Ewing's sarcomas, liposarcomas, and malignant fibrous histiocytomas were heterogeneous in their expression of p21WAF1/CIP1. Combining p53 and p21WAF1/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 p21WAF1/CIP1. There was no correlation between Ki-67 and p21WAF1/CIP1 or p53 staining. Our results show that soft tissue sarcomas, independent of their histologic subtype, frequently express p21WAF1/CIP1 which is probably important in their tumorigenesis. Additionally, p21WAF1/CIP1 may play a role in determining the efficacy of various cell cycle-directed therapies in soft tissue sarcomas.
Pindzola
J A
JA
Department of Pathology, Anatomy and Cell Biology, Jefferson Medical College, Philadelphia, PA, USA.
Palazzo
J P
JP
Kovatich
A J
AJ
Tuma
B
B
Nobel
M
M
D050759:Cyclin-Dependent Kinase Inhibitor p21; D016213:Cyclins / Q000378:metabolism*; D004791:Enzyme Inhibitors / Q000378:metabolism*; D006801:Humans; D007124:Immunoenzyme Techniques; D019394:Ki-67 Antigen / Q000378:metabolism*; D012509:Sarcoma / Q000378:metabolism* / Q000473:pathology; D012983:Soft Tissue Neoplasms / Q000378:metabolism* / Q000473:pathology; D016159:Tumor Suppressor Protein p53 / Q000378:metabolism*
C493956:CDKN1A protein, human; D050759:Cyclin-Dependent Kinase Inhibitor p21; D016213:Cyclins; D004791:Enzyme Inhibitors; D019394:Ki-67 Antigen; D016159:Tumor Suppressor Protein p53