Ovarian cancer p53 mutation is associated with tumor microvessel density.
OBJECTIVE
The objective of this study was to investigate the relationship between microvessel density, as measured by CD31 staining, and histopathologic factors as well as p53 tumor suppressor gene mutation in ovarian cancer.


METHODS
Ovarian cancers (n = 77) were analyzed for p53 gene mutations and CD31 immunohistochemical expression. Histopathologic and mutational data were related to CD31 staining utilizing the Mantel correlation statistic. The microvessel density was scored by averaging counts from three high-power (200x) fields. Survival was based upon maximizing the hazard ratio.


RESULTS
The mean microvessel density counts based on CD31 staining (vessels/HPF) for each FIGO stage and mutation type are as follows: Stage I (10.2), Stage II (10.7), Stage III (13.8), Stage IV (22.0), wild-type p53 (9.3), missense p53 mutation (14.4), and null p53 mutation (23.1). There was a significant correlation between microvessel density count and FIGO stage (P = 0.026), grade (P = 0.04), and p53 mutation type (P = 0.02). Median survival was more than doubled (6.4 vs 2.9 years; P = 0.009) for tumors with microvessel density counts less than or equal to 14 vessels/HPF.


CONCLUSIONS
These data are consistent with the hypothesis that ovarian cancer p53 mutation functions to directly influence angiogenesis, which in turn compromises disease-specific survival. It also suggests validity to targeting p53 alterations with gene replacement as well as the use of antiangiogenesis agents as novel molecular-based therapeutics for ovarian cancer.
Goodheart
Michael J
MJ
Division of Gynecologic Oncology, Department of Obstetrics and Gynecology, Holden Comprehensive Cancer Center, University of Iowa Hospitals and Clinics, Iowa City, Iowa 52242, USA.
Vasef
Mohammad A
MA
Sood
Anil K
AK
Davis
Charles S
CS
Buller
Richard E
RE
D005260:Female; D016158:Genes, p53; D006801:Humans; D007150:Immunohistochemistry; D009154:Mutation; D009367:Neoplasm Staging; D009389:Neovascularization, Pathologic / Q000235:genetics / Q000378:metabolism; D010051:Ovarian Neoplasms / Q000098:blood supply* / Q000235:genetics* / Q000473:pathology; D010865:Pilot Projects; D019408:Platelet Endothelial Cell Adhesion Molecule-1 / Q000378:metabolism
D019408:Platelet Endothelial Cell Adhesion Molecule-1