Review of Clinical Pharmacology and Pharmacokinetics – International Edition 39(2): 105-117, doi: 10.61873/XWJX3729
Association of immunohistochemical expression of Bcl-2 with estrogen ER-PR receptors and HER2 and Ki67 in breast cancer
Paraskevi Konstantinidi‡§, Petros Papagiorgis|, Nikolaos Thalassinos§, Olympia Tzaida‡, Fragkiski Anthouli-Anagnostopoulou§‡ Pathological Anatomy Laboratory, Metaxa Cancer Hospital, Piraeus, Greece§ Department of Biomedical Sciences, Faculty of Health and Caring Sciences, University of West Attica, Athens, Greece| St. Josef Psychiatric Hospital AMEOS, Oberhausen, Germany
© Paraskevi Konstantinidi, Petros Papagiorgis, Nikolaos Thalassinos, Olympia Tzaida, Fragkiski Anthouli-Anagnostopoulou. This is an open access article distributed under the terms of the Creative Commons Attribution License (CC BY 4.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. Citation:
Konstantinidi P, Papagiorgis P, Thalassinos N, Tzaida O, Anthouli-Anagnostopoulou F (2025) Association of immunohistochemical expression of Bcl-2 with estrogen ER-PR receptors and HER2 and Ki67 in breast cancer. Review of Clinical Pharmacology and Pharmacokinetics – International Edition 39(2): 105-117. https://doi.org/10.61873/XWJX3729 |  |
Abstract
Background: Breast carcinoma is among the three most common types of cancer worldwide, including lung cancer and colon cancer, regardless of gender. The Bcl -2 oncogene is involved in a number of malignant neoplasms, including leukaemia and lymphoma, through the regulation of the cell apoptosis process. Aim: The main purpose of the present study is to investigate the association of Bcl-2 with other molecular parameters of significant prognostic and predictive value for disease and more specifically the ER and PR receptors, along with HER-2 and Ki-67 (MIB-1). Methodology: Immunohistochemical assessment of Bcl-2, ER and PR receptors, HER-2 and Ki-67 was conducted in a case series of 100 surgically resected primary breast carcinomas and the association of Bcl-2 with the other biomarkers was statistically investigated. Results: High (3+) Bcl-2 expression was observed in 65% of cases, moderate (2+) in 12%, low (1+) in 4% and negative expression in 19%. Association of Bcl-2 with ER-PR receptors and HER2 and Ki67 was conducted with Fisher’s exact and Chi square (x 2 ) test of Cramer’s V statistics tests were performed where appropriate. Bcl -2 oncogene was positively and highly associated with estrogen ER receptors (Phi=0.760, p =<0.0001); the findings of the association of Bcl -2 oncogene with PR progesterone receptors were similar: a positive association was found between the two specific biomarkers (Phi=0.626, p =<0.0001). Finally, negative association of Bcl-2 with HER2 (Phi=-0.350, p =<0.0001). Conclusion: Considering the association of Bcl-2 expression with the expression of genes that are related to therapy prediction (ER and PR) it remains to be ascertained whether Bcl-2 could be used as a potential predictive marker. Moreover, the negative association of Bcl-2 with Ki67 and HER2 should be furthermore investigated for its association with disease outcome and response to targeted therapy. Overall, this study suggests that Bcl-2 should be further tested for its incorporation into a multivariate prediction model for breast cancer therapy. In addition, more investigations are required into targeted anti-Bcl-2 therapy may be used to modify responses to current breast cancer therapy, in order to reduce resistance.
Keywords
breast cancer, Bcl -2 oncogene, ER – PR receptors , HER2, immunohistochemistry