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.


OBJECTIVE
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.
Drobnjak
M
M
Department of Pathology, Memorial Sloan-Kettering Cancer Center, New York, NY 10021.
Latres
E
E
Pollack
D
D
Karpeh
M
M
Dudas
M
M
Woodruff
J M
JM
Brennan
M F
MF
Cordon-Cardo
C
C
D000328:Adult; D000911:Antibodies, Monoclonal; D015870:Gene Expression; D006801:Humans; D007150:Immunohistochemistry; D019394:Ki-67 Antigen; D009363:Neoplasm Proteins / Q000032:analysis*; D009687:Nuclear Proteins / Q000032:analysis*; D010641:Phenotype; D011237:Predictive Value of Tests; D011379:Prognosis; D012509:Sarcoma / Q000737:chemistry* / Q000235:genetics / Q000473:pathology; D016019:Survival Analysis; D016159:Tumor Suppressor Protein p53 / Q000032:analysis* / Q000235:genetics
D000911:Antibodies, Monoclonal; D019394:Ki-67 Antigen; D009363:Neoplasm Proteins; D009687:Nuclear Proteins; D016159:Tumor Suppressor Protein p53