Co-expression of VEGF and CA9 in ovarian high-grade serous carcinoma and relationship to survival

Poor prognosis in ovarian high-grade serous carcinoma (HGSC) is largely related to resistance to chemotherapy. Tumour hypoxia is known to be associated with chemotherapy resistance. Stabilisation of hypoxia-inducible factor-1α upregulates the expression of downstream genes such as carbonic anhydrase 9 (CA9) and vascular endothelial growth factor (VEGF). This study was undertaken to analyse the hypoxia profile as indicated by the co-expression of VEGF and CA9 and its correlation with survival. VEGF and CA9 expressions were examined in tissue microarray of 97 cases of ovarian high-grade serous carcinoma using immunohistochemistry. High expression of either VEGF or CA9, individually, was associated with decreased overall survival (p = 0.006 and p = 0.05 respectively). Combined high expression of both markers, to give a ‘hypoxia profile’, was associated with chemotherapy resistance (p = 0.036) and showed worse overall survival with a significant p value (p = 0.001). Using multivariate analysis, hypoxia profile was an independent prognostic factor for overall survival (p = 0.028). The combined high expression CA9 and VEGF phenotype, described as high hypoxia profile group, was significantly associated with increased resistance to chemotherapy and poor overall survival. This group may benefit from combined targeted therapy for effective response in ovarian HGSC.