Elevated CAIX expression is associated with an increased risk of distant failure in early-stage cervical cancer

Tumor hypoxia is associated with adverse outcome in many malignancist. The goal of this study was to determine if elevated expression of carbonic, anhydrase EX (CAIX), a biomarker of hypoxia, predicts fot recurrence in early-stage cervical cancer, The charts of all patients with early-stage, cervical cancer, primarily FIGO IB, treated by radical hysterectomy at our institution from 1988-2001 were reviewed, Adequate pathologic specimens from patients who recurred or who had at least three years follow-up and remianed, disease-free were stained for CAIX. An immunohistochemical score (IHC) was generated from the extent/ intensity of staining. Outcome, as-measured. by freedom from recurrence (FFR); distant metastases (FFDM) and local recurrence (FFLR), was analyzed as a function of age, IHC, lymph node status (LN) and histology. Forty-two relapsing patients and 76 non-relapsing patients were evaluated. In univariate analysis, +LN, though not IHC or histology, was a significant predictor of any recurrence. Both +LN and higher IHC, were associated with decreased FFDM but not FFLR. Patients with both +LN and elevated IHC more frequently exhibited distant metastises as first site of failure. (5-yedr FFDM 50%) than patients with only. +LN, elevated IHC or neither feature (70, 85 and 95%, respectively, p = 0.0004). In multivariable analysis, only +LN was significantly associated with poorer FFDM (hazard ratio 4.6, p=0.0015) though there was a strong trend with elevated CAIX expression (p = 0.069). Elevated CAIX expressions is associated with more frequent distant metastases in early-stage cervical cancer, suggesting that patients with this characteristic may benefit from more aggressive treatment.