Prognostic relevance of carbonic anhydrase-IX in high-risk, early-stage cervical cancer: A Gynecologic Oncology Group study

Abstract

Objectives This study aimed 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. Methods 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. Results 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 , 2–2.9 , 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). Conclusions 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.