Observations on Tumor and Metastatic Suppressor Gene Status in Human Fibrous Neoplasms with Particular Emphasis on p53 and nm23

Abstract

Eighty-two soft-tissue sarcomas, including 50 patients with dermatofibrosarcoma protuberans (DFSP), 16 patients with fibrosarcomas (FS), and 16 patients with malignant fibrous histiocytoma (MFH), were investigated for the presence of p53 mutations and for p53, nm23 immunoreactivity with silver-staining polymerase chain reaction-single-strand conformation polymorphism and immunohistochemistry methods. The total mutation rate of p53 gene was 23% (3 of 50 DFSP, 7 of 16 FS and 9 of 16 MFH). Of 82 tumor samples, 22% (2 of 50 DFSP, 6 of 16 FS, and 10 of 16 MFH) were positive for p53 immunostaining. p53 gene mutation and expression were low in DFSP (6.0%; 4.0%) but high in FS (43.8%; 37.5%) and in MFH (56.3%; 62.5%). NDPK/nm23 expression was high in DFSP (84.0%) but was low in FS (31.3%) and in MFH (18.8%). High levels of p53 gene mutation and expression correlated with metastasis and degree of malignancy. On the contrary, low levels of NDPK/nm23 expression correlated with metastasis and degree of malignancy of human fibrous neoplasms. p53 mutations in soft-tissue sarcomas have a similar spectrum to those in carcinomas. Determination of p53 gene mutation and expression in combination with low nm23/NDPK expression may help predict metastasis and degree of malignancy of fibrous neoplasms. The precise association between the p53 gene and nm23 gene remains to be established.