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


METHODS
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.
Goodheart
Michael J
MJ
Division of Gynecologic Oncology, Department of Obstetrics and Gynecology, University of Iowa Hospital and Clinics, Iowa City, Iowa, USA. michael-goodheart@uiowa.edu
Ritchie
Justine M
JM
Rose
Stephen L
SL
Fruehauf
John P
JP
De Young
Barry R
BR
Buller
Richard E
RE
D017024:Chemotherapy, Adjuvant; D004252:DNA Mutational Analysis; D018572:Disease-Free Survival; D005260:Female; D016158:Genes, p53; D006801:Humans; D007150:Immunohistochemistry; D008875:Middle Aged; D009362:Neoplasm Metastasis; D009364:Neoplasm Recurrence, Local / Q000235:genetics*; D009389:Neovascularization, Pathologic; D010051:Ovarian Neoplasms / Q000098:blood supply / Q000188:drug therapy / Q000235:genetics* / Q000473:pathology*; D011379:Prognosis; D012044:Regression Analysis; D012307:Risk Factors