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The relationship of molecular markers of p53 function and angiogenesis to prognosis of stage I epithelial ovarian cancer
Journal article   Open access   Peer reviewed

The relationship of molecular markers of p53 function and angiogenesis to prognosis of stage I epithelial ovarian cancer

Michael J. Goodheart, Justine M Ritchie, Stephen L. Rose, John P Fruehauf, Barry R De Young and Richard E Buller
Clinical Cancer Research, Vol.11(10), pp.3733-3742
05/15/2005
DOI: 10.1158/1078-0432.CCR-04-0056
PMID: 15897570
url
https://doi.org/10.1158/1078-0432.CCR-04-0056View
Published (Version of record) Open Access

Abstract

Purpose: Multiple angiogenic factors may influence tumor progression and metastasis. Several are modified by the p53 gene. We sought to identify molecular markers for high-risk stage I epithelial ovarian cancers. Experimental design: Seventy-seven consecutive stage I epithelial ovarian cancers were evaluated for p53, CD31 microvessel density, thrombospondin-1, vascular endothelial growth factor (VEGF), p21 immunohistochemical staining, and p53 gene mutations. Molecular marker impact upon disease-specific survival, disease recurrence, and distant recurrence was evaluated with Cox regression. Results: There were 12 deaths from disease. Twelve of the 77 tumors contained p53 mutations-10 missense and 3 null (one tumor had two mutations). Fesddration Internationale des Gynaecologistes et Obstetristes substage (IA/IB versus IC; P < 0.001) and VEGF staining (P = 0.02) were significant in bivariate models with relationship to disease-specific survival. Stage (P = 0.0004), grade (P = 0.008), histology (P = 0.0025), p53 dysfunction (positive stain and/or mutation; P = 0.048), and microvessel density (P = 0.04) were significant in bivariate models with relationship to time to recurrence. In multivariate analyses among stage IC patients, failure to receive chemotherapy and microvessel density were associated with disease-specific survival, time to recurrence, and time to distant recurrence with hazard ratios of 4.8 to 44.1. Conclusions: The p53-dependent molecular markers of angiogenesis are of limited utility in developing a clinical strategy for postoperative management of stage I ovarian carcinoma. Microvessel density impacts survival and metastasis for high-risk stage IC disease. Adjuvant chemotherapy is necessary, but not sufficient, for cure of high-risk stage I epithelial ovarian cancers.
 Obstetrics and Gynecology

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