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The Relationship of Molecular Markers of p53 Function and Angiogenesis to Prognosis of Stage I Epithelial Ovarian Cancer
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...
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Published in: | Clinical cancer research 2005-05, Vol.11 (10), p.3733-3742 |
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Main Authors: | , , , , , |
Format: | Article |
Language: | English |
Subjects: | |
Citations: | Items that this one cites Items that cite this one |
Online Access: | Get full text |
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Summary: | 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. |
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ISSN: | 1078-0432 1557-3265 |
DOI: | 10.1158/1078-0432.CCR-04-0056 |