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Prognostic Significance of Carbonic Anhydrase IX in Breast Camcer Patients

Carbonic anhydrase IX is an endogenous marker for tumor hypoxia. CD105 is a proliferation-associated and hypoxia-inducible protein abundantly expressed in angiogenic endothelial cells. 8-hydroxy-2′ -deoxyguanosine (8-OHdG) is an oxidative DNA lesion. We examined the effect of these three markers on overall survival and disease-free survival of breast cancer patients. Immunohistochemistry for CA IX, CD105 and 8-OHdG was performed on paraffin-embedded tumor tissues from forty female breast cancer patients. Fisher’ s exact test, chi-square test, Spearman rank correlation coefficient (ρ ), Kaplan-Meier univariate method and the Cox proportional hazards regression model were used for statistical analysis. CA IX and CD105 expressions were higher in areas with moderate to severe tumor necrosis compared to areas with minimal tumor necrosis (P=0.044 for both). Expressions of CA IX and CD 105 above the median values were significantly associated with lymph nodes involvement (P=0.004 and P=0.025 respectively). Occurrence of relapse was significantly higher in patients with higher CA IX expression (P=0.008), more extensive tumor necrosis (P=0.008), in patients with grade III tumors (P=0.04) as well as in patients with positive lymph nodes (P<0.001). Univariate analysis showed that high CAIX expression was significantly associated with shorter OS (P<0.001) and shorter DFS (P<0.001). Neither CD105 nor 8-OHdG expressions showed any effect on OS and DFS. Multivariate analysis showed that high CAIX expression and positive lymph nodes were strong independent prognostic indicators for shorter OS (P=0, 039 and P=0.005 respectively) and shorter DFS (P=0.024 and P=0.011, respectively). In this study, hypoxia marker CA IX was a significant parameter of tumor aggressiveness and poor prognosis of breast cancer patients.

carbonic anhydrase IX ; breast cancer patients

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