Analysis of the p53-hMDM2-p21 (WAF1/CIP1) Cell Cycle Regulation Pathway in Malignant Fibrous Histiocytomas

Abstract

This study was undertaken to analyze patterns of expression of critical cell cycle regulators (CCR) involved in the p53 pathway in malignant fibrous histiocytomas (MFH). Protein expression was assessed using immunohistochemistry analyzing p53, hMDM2 and p21 (WAF1/CIP1) phenotypes. p53- and hMDM2-positive phenotypes were found to be associated with low p21 levels (p<0.01). Positive hMDM2 phenotype did not correlate with any hMDM2 mutations, which in our tumor collective were not found. High-grade MFH differed from MFH grade I and II concerning higher p53 and lower p21 levels, while hMDM2 expression was independent of grade. Inclusion of categorized values into a Cox regression study proved the independent prognostic relevance of p53, hMDM2 and p21 phenotypes.