Prognostic implications of p53 nuclear overexpression and high proliferation index of Ki-67 in adult soft-tissue sarcomas

Background: Morphologically similar soft-tissue sarcomas may behave in very different fashions, making it difficult to predict clinical outcomes and to properly design therapeutic interventions. In a preliminary study, we observed that TP53 mutations and nuclear overexpression of p53 protein were frequent events in soft-tissue sarcoma, and we noticed an association between p53-positive phenotype and poor clinical outcome. Purpose: We examined the potential clinical relevance of p53 overexpression in adults with soft-tissue sarcomas. We also studied the clinical implications of a high proliferation index. Methods: A cohort of 174 adults with soft-tissue sarcomas were analyzed using anti-p53 and anti- Ki-67 antibodies and immunohistochemical assays on consecutive fresh frozen tissue samples. Results: We observed a significant association between p53 nuclear overexpression and tumor grade (P = .001) and tumor size (P = .01). Patients displaying a p53- positive phenotype had significantly reduced survival (P = .02). Similarly, a significant difference was observed between high proliferation index and tumor grade (P<.001) and reduced patient survival (P = .03). A high Ki-67 proliferation index was detected in association with p53 nuclear overexpression. Conclusions: Overexpression of p53 protein and a high proliferation index strongly correlate with poor clinical outcome and reduced survival in patients having soft-tissue sarcomas. [J Natl Cancer Inst 86:549-554,1994].