Apoptosis regulator Bcl-2 is an independent prognostic marker for worse overall survival in triple-negative breast cancer patients



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.


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).


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).


Elevated expression of Bcl-2 was an independent prognostic factor for poorer OS in TNBC and as such a significant marker for tumor aggressiveness.

Post author correction




Petar Ozretic, Ilija Alvir, Bozena Sarcevic, Zeljko Vujaskovic, Zrinka Rendic-Miocevic, Ana Roguljic, Lidija Beketic-Oreskovic

Article History


Financial support: This work was supported by a grant from the Ministry of Science, Education and Sports of the Republic of Croatia (grant no. 074-0982464-1187).
Conflict of interest: The authors declare they have no conflict of interest.
Meeting presentation: The results published in this paper were presented at the 11th Central European Oncology Congress (CEOC) in Opatija, Croatia, June 17-20, 2015, and the 10th European Breast Cancer Conference (EBCC-10) in Amsterdam, Netherlands, March 9-11, 2016.

This article is available as full text PDF.

  • If you are a Subscriber, please log in now.

  • Article price: Eur 36,00
  • You will be granted access to the article for 72 hours and you will be able to download any format (PDF or ePUB). The article will be available in your login area under "My PayPerView". You will need to register a new account (unless you already own an account with this journal), and you will be guided through our online shop. Online purchases are paid by Credit Card through PayPal.
  • If you are not a Subscriber you may:
  • Subscribe to this journal
  • Unlimited access to all our archives, 24 hour a day, every day of the week.



  •  Laboratory for Hereditary Cancer, Division of Molecular Medicine, Rudjer Boskovic Institute, Zagreb - Croatia
  •  Department of Gynecologic Oncology, University Hospital for Tumors, Sestre Milosrdnice Clinical Hospital Center, Zagreb - Croatia
  •  Department of Pathology, University Hospital for Tumors, Sestre Milosrdnice Clinical Hospital Center, Zagreb - Croatia
  •  Division of Translational Radiation Sciences, Department of Radiation Oncology, University of Maryland School of Medicine, Baltimore, Maryland - USA
  •  Department of Radiotherapy and Internal Oncology, University Hospital for Tumors, Sestre Milosrdnice Clinical Hospital Center, Zagreb - Croatia
  • Department of Clinical Oncology, University of Zagreb School of Medicine, Zagreb - Croatia

Article usage statistics

The blue line displays unique views in the time frame indicated.
The yellow line displays unique downloads.
Views and downloads are counted only once per session.

No supplementary material is available for this article.