Background: The objective of this study was to examine the prognostic significance of carbonic anhydrase IX (CAIX), an endogenous marker for tumor hypoxia; the cellular tumor antigen p53; and the apoptosis regulator Bcl-2, in triple-negative breast cancer (TNBC) patients.
Methods: Immunohistochemically determined expression of CAIX, p53, Bcl-2 and proliferation factor Ki-67, analyzed in 64 paraffin-embedded TNBC tissue samples, was used to assess their relation to clinicopathological variables and prognostic implications for overall survival (OS).
Results: Bcl-2 expression was negatively correlated with histological grade of tumor, while expression of p53 was positively correlated with the same clinical variable (p = 0.036 and p = 0.033, respectively). The p53 expression was also positively correlated with tumor size (p = 0.010). Survival analysis showed that patients with high Bcl-2 expression (above cutoff value determined by receiver operator characteristic [ROC] curve analysis) had shorter OS (p = 0.020). The same was observed for patients with tumors larger than 5 cm (p = 0.034) or positive lymph nodes (p = 0.004). Among all 3 examined markers, multivariate analysis showed that only Bcl-2 expression was a strong independent prognostic indicator for decreased OS (hazard ratio [HR] = 15.16, 95% confidence interval [95% CI], 2.881-79.727, p = 0.001).
Conclusions: Elevated expression of Bcl-2 was an independent prognostic factor for poorer OS in TNBC and as such a significant marker for tumor aggressiveness.
Keywords: B-cell lymphoma 2; Carbonic anhydrase IX; Ki-67 antigen; Triple-negative breast neoplasms; Tumor biomarkers; Tumor suppressor protein p53.