P53 overexpression in human soft tissue sarcomas: Relation to biological aggressiveness

Abstract

The tumor suppressor protein p53 is overexpressed in a large fraction of human tumors. It has been supposed that p53 abnormalities may be an early event that contributes to the neoplastic transformation; alternatively, p53 overexpression might be related to progression toward more aggressive tumor phenotypes. The aim of the present work was to better clarify the role of p53 overexpression in human soft tissue sarcomas (IISTS). p53 immunohistochemistry analysis using the Pab 1801 was performed in frozen samples of HSTS obtained from 61 patients. Tumors were classified according to the WHO criteria, histologic grading was based on the criteria of Enzinger and Weiss, and DNA ploidy and S-phase determination was performed by flow cytometrical analysis. Of all the HSTS we analyzed, p53 protein over-expression occurred more frequently in G3 grade tumors (p < 0.01), HSTS of III A-B stage (p = 0.02) and in aneuploid tumors (p < 0.01). The association of p53 overexpression with parameters of biological aggressiveness suggests an involvement of p53 in the neoplastic progression of HSTS. This assumption is supported by the findings that in tumors with a mixed diploid/aneuploid neoplastic cell population p53 protein expression was significantly (p < 0.01) higher in the aneuploid cell subpopulation. In conclusion, our study suggests that overexpression of p53 is present mainly in the most biologically aggressive forms of HSTS and may therefore represent a neoplastic progression index possibly useful for prognostic purposes.