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

被引:60
作者
Goodheart, MJ
Ritchie, JM
Rose, SL
Fruehauf, JP
De Young, BR
Buller, RE
机构
[1] Univ Iowa Hosp & Clin, Dept Obstet & Gynecol, Div Gynecol Oncol, Iowa City, IA 52242 USA
[2] Univ Iowa Hosp & Clin, Holden Comprehens Canc Ctr, Dept Pathol, Iowa City, IA 52242 USA
[3] Univ Iowa Hosp & Clin, Holden Comprehens Canc Ctr, Dept Biostat, Iowa City, IA 52242 USA
[4] Oncotech Inc, Irvine, CA USA
关键词
D O I
10.1158/1078-0432.CCR-04-0056
中图分类号
R73 [肿瘤学];
学科分类号
100214 ;
摘要
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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收藏
页码:3733 / 3742
页数:10
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