To determine whether carbonic anhydrase-IX (CA-IX) was associated with progression-free survival (PFS) and overall survival (OS) in women with high-risk, early-stage cervical cancer treated with adjuvant pelvic radiotherapy with or without radiosensitizing chemotherapy.
CA-IX expression was detected using an immunohistochemistry assay and categorized as low when ≤80% of tumor cells exhibited CA-IX staining and high when >80% tumor cells display CA-IX staining. Associations between CA-IX expression and clinical characteristics, angiogenesis marker expression and clinical outcome were evaluated.
High CA-IX expression was observed in 35/166 (21.1%) of cases. CA-IX expression was not associated with age, race, stage, cell type, grade, positive margins, parametrial extensions, positive lymph nodes or lymphovascular space invasion but was associated with tumor size categorized as <2 cm, 2-2.9 cm, or ≥3 cm (high expression: 4.7% vs. 23.2% vs. 32.5%, p=0.003) and cervical invasion confined to the inner two thirds compared with the outer third of the cervix (high expression: 6.1% vs. 23.7%, p=0.028). CA-IX expression was not associated with immunohistochemical expression of p53, CD31, CD105, thrombospondin-1 or vascular endothelial growth factor-A. Women with high versus low CA-IX expression had similar PFS (p=0.053) and significantly worse OS (p=0.044). After adjusting for prognostic clinical covariates, high CA-IX expression was an independent prognostic factor for PFS (hazard ratio [HR]=2.12; 95% confidence interval [CI]=1.13 -3.95; p=0.019) and OS (HR=2.41; 95% CI=1.24-4.68; p=0.009).
Tumor hypoxia measured by immunohistochemical expression of CA-IX is an independent prognostic factor for both PFS and OS in high-risk, early-stage cervical cancer.