ABSTRACT
PURPOSE: Angiogenesis has a vital role in tumor growth and metastasis, and vascular endothelial growth factor (VEGF) represents a potent cytokine in this process. However, the influence of VEGF in ovarian cancer remains controversial. Interest has focused on the use of antiangiogenic drugs in ovarian cancer. This study aims to establish the pattern of expression and effect on prognosis of VEGF in a large population of ovarian cancer patients and to potentially identify a cohort in whom antiangiogenic therapy is appropriate. EXPERIMENTAL DESIGN: Using a tissue microarray of 339 primary ovarian cancers, the expression of VEGF was assessed immunohistochemically. Coupled to a comprehensive database of clinicopathologic variables, its effect on these factors and survival was studied. RESULTS: Tumors expressing high levels of VEGF had significantly poorer survival (P = 0.04). Factors shown to predict prognosis independently of each other were age, International Federation of Gynecologists and Obstetricians stage, and the absence of macroscopic disease after surgery. VEGF was independently predictive of prognosis on multivariate analysis (P = 0.02). There was no correlation between VEGF and any clinicopathologic variable. High expression of VEGF was seen in only 7% of the tumors, suggesting that the role of antiangiogenic drugs may be limited to a small subset of patients. CONCLUSION: High VEGF expression occurs in a small proportion of ovarian cancers, and this independently predicts poor prognosis. The small percentage of tumors with high levels of VEGF activity suggests that the role of bevacizumab may potentially be limited to a few patients; these patients could be targeted by molecular profiling.
Subject(s)
Biomarkers, Tumor/analysis , Ovarian Neoplasms/metabolism , Vascular Endothelial Growth Factor A/biosynthesis , Adult , Aged , Aged, 80 and over , Angiogenesis Inhibitors/administration & dosage , Antineoplastic Agents/administration & dosage , Drug Delivery Systems , Female , Humans , Immunohistochemistry , Kaplan-Meier Estimate , Middle Aged , Neovascularization, Pathologic/drug therapy , Ovarian Neoplasms/drug therapy , Ovarian Neoplasms/mortality , Prognosis , Tissue Array AnalysisABSTRACT
PURPOSE: There is evidence that IFN gamma plays an important role in ovarian cancer development. IFN gamma produces numerous antitumor effects and it may be evasion of these effects which allows tumor progression. We postulate that genetic instability in tumor cells may lead to modulation of expression of the IFN gamma receptor, thus leading to altered tumor biology and patient prognosis. This hypothesis would support the theory of immunoediting in ovarian cancer. EXPERIMENTAL DESIGN: Using tissue microarray technology of 339 primary ovarian cancers, the expression of IFN gamma receptor was assessed immunohistochemically. Coupled to a comprehensive database of clinicopathologic variables, its effect on these factors was studied. RESULTS: Tumors expressing high levels of IFN gamma receptor had significantly improved survival (P=0.017) compared with tumors expressing low levels of the receptor; this was also seen with complete receptor loss (P=0.014). Factors shown to predict prognosis independently of each other were the following: age, International Federation of Gynecologists and Obstetricians stage, and the absence of macroscopic disease after surgery. The level of IFN gamma receptor expression and complete receptor loss were independently predictive of prognosis on multivariate analysis. There was no correlation between receptor status and any of the standard clinicopathologic variables. CONCLUSIONS: Loss of IFN gamma receptor independently predicts poor prognosis in ovarian cancer. Loss of receptor expression may be responsible for the limited success in the therapeutic use of IFN gamma in ovarian cancer trials and highlights a subgroup of high expressing IFN gamma receptor tumors which are more likely to be susceptible to such treatments.
