p53 Mutations and Tumor Progression in Well-differentiated Liposarcoma and Dermatofibrosarcoma Protuberans

Mutations of the tumor suppressor gene p53 have been identified in a wide variety of human tumors, including soft tissue sarcomas. Most missense mutations of p53 increase the half-life of the protein resulting in its accumulation in the nucleus. Immunohistochemical staining with a monoclonal antibody PABI801 (Oncogene Science, Uniondale, NY) detects the intranuclear accumulation of p53 protein in formalin-fixed tissue, and, thus, indicates the presence of missense mutations within the p53 gene. We compared p53 immunoreactivity in paraffin sections of low-grade sarcomas that progressed to high-grade lesions with low-grade sarcomas that had not progressed to high-grade lesions to determine if (1) histologic progression is associated with increasing incidence of p53 missense mutations, and (2) p53 missense mutations within low-grade areas are predictive of which lesions undergo histologic progression. To examine these questions we studied well-differentiated liposarcoma with and without dedifferentiation and dermatofibrosarcoma protuberans with and without areas of fibrosarcoma. Nuclear p53 immunoreactivity was detected in 48% (12/25) of well-differentiated liposarcoma with dedifferentiation compared to only 6% (1/17) of well-differentiated liposarcoma alone. p53 nuclear immunoreactivity was also detected in 25% (4/16) of dermatofibrosarcoma protuberans with fibrosarcoma, and in 0% (0/24) of dermatofibrosarcoma protuberans lacking fibrosarcoma. In cases of well-differentiated liposarcoma with dedifferentiation and dermatofibrosarcoma protuberans with fibrosarcoma displaying immunoreactivity, the staining occurred almost exclusively in the high-grade areas and very infrequently in the low-grade regions as well. We conclude that histologic progression of well-differentiated liposarcoma and dermatofibrosarcoma protuberans is associated with increased nuclear p53 immunoreactivity. Since p53 immunoreactivity occurs infrequently in the low-grade areas of those sarcomas that had transformed to higher grade lesions, it does not appear to be a useful predictor of tumor progression in low-grade lesions. Int J Surg Pathol 3(1):35-42, 1995