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Cyclooxygenase-2 and Bcl-2 expression in patients with triple-negative breast cancer
, 1, 1, 1
Affiliations- Department of Cancer Prevention, Medical University of Warsaw, Warsaw, Poland
- Students’ Scientific Organization of Cancer Cell Biology, Department of Cancer Prevention, Medical University of Warsaw, Warsaw, Poland
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Abstract
Introduction.Triple-negative breast cancer (TNBC) is a rare type of breast cancer associated with lack of expression of estrogen and progesterone receptors and the HER2 protein. It is characterized by a poor outcome and chemotherapy resistance. Cyclooxygenase-2 (COX-2) is a constitutional enzyme responsible for prostaglandin synthesis, present in neoplastic cells and premalignant lesions. The B-cell lymphoma 2 (Bcl-2) protein is considered one of the most potent apoptosis-regulating agents, assuring body homeostasis.
Material and methods.The aim of the present study was to evaluate the immunohistochemical (IHC) profile of COX-2 and Bcl-2 expression in patients suffering from TNBC in order to obtain more detailed data on additional factors negatively influencing TNBC outcome. The IHC evaluation of COX-2 and Bcl-2 expression among 21 women with diagnosis of TNBC was performed.
Results.The most common histological subtype was invasive ductal cancer of no special type. COX-2 was present in all examined samples with moderate to strong expression detected in 20 of 21 cases. There was a positive correlation between histological grade (G) and COX-2 expression (p = 0.002). Bcl-2 was present in all examined samples. The analysis showed that tumours presenting highly positive expression of Bcl-2 accounted for the majority of examined cases (57.2%).
Conclusions.The achieved results might lead to a conclusion that COX-2 and Bcl-2 high expression in TNBC may be linked to tumour aggressiveness and poor overall survival. However, before their consideration as additional markers to be used in routine histological examinations and breast cancer grading, it will be necessary to undertake further studies.
Abstract
Introduction.Triple-negative breast cancer (TNBC) is a rare type of breast cancer associated with lack of expression of estrogen and progesterone receptors and the HER2 protein. It is characterized by a poor outcome and chemotherapy resistance. Cyclooxygenase-2 (COX-2) is a constitutional enzyme responsible for prostaglandin synthesis, present in neoplastic cells and premalignant lesions. The B-cell lymphoma 2 (Bcl-2) protein is considered one of the most potent apoptosis-regulating agents, assuring body homeostasis.
Material and methods.The aim of the present study was to evaluate the immunohistochemical (IHC) profile of COX-2 and Bcl-2 expression in patients suffering from TNBC in order to obtain more detailed data on additional factors negatively influencing TNBC outcome. The IHC evaluation of COX-2 and Bcl-2 expression among 21 women with diagnosis of TNBC was performed.
Results.The most common histological subtype was invasive ductal cancer of no special type. COX-2 was present in all examined samples with moderate to strong expression detected in 20 of 21 cases. There was a positive correlation between histological grade (G) and COX-2 expression (p = 0.002). Bcl-2 was present in all examined samples. The analysis showed that tumours presenting highly positive expression of Bcl-2 accounted for the majority of examined cases (57.2%).
Conclusions.The achieved results might lead to a conclusion that COX-2 and Bcl-2 high expression in TNBC may be linked to tumour aggressiveness and poor overall survival. However, before their consideration as additional markers to be used in routine histological examinations and breast cancer grading, it will be necessary to undertake further studies.
Keywords
Bcl-2; cyclooxygenase-2; immunohistochemistry; prognostic factors; triple-negative breast cancer
About this articleTitle
Cyclooxygenase-2 and Bcl-2 expression in patients with triple-negative breast cancer
Journal
Nowotwory. Journal of Oncology
Issue
Article type
Research paper (original)
Pages
211-218
Published online
2022-06-10
Page views
3937
Article views/downloads
247
DOI
Bibliographic record
Nowotwory. Journal of Oncology 2022;72(4):211-218.
Keywords
Bcl-2
cyclooxygenase-2
immunohistochemistry
prognostic factors
triple-negative breast cancer
Authors
Anna Liszcz-Tymoszuk
Marta Fudalej
Andrzej Deptała
Anna M. Badowska-Kozakiewicz
References (35)- Wojciechowska U, Didkowska J, Zatoński W. Prognosis of maliginant cancers’ morbidity and mortality in Poland in 2025. In: Malignant tumors registration. , Warsaw 2009.
- Dawood S. Triple-Negative Breast Cancer. Drugs. 2010; 70(17): 2247–2258.
- Moris D, Kontos M, Spartalis E, et al. The Role of NSAIDs in Breast Cancer Prevention and Relapse: Current Evidence and Future Perspectives. Breast Care (Basel). 2016; 11(5): 339–344.
- Ristimäki A, Sivula A, Lundin J, et al. Prognostic significance of elevated cyclooxygenase-2 expression in breast cancer. Cancer Res. 2002; 62(3): 632–635.
- Fornetti J, Jindal S, Middleton KA, et al. Physiological COX-2 expression in breast epithelium associates with COX-2 levels in ductal carcinoma in situ and invasive breast cancer in young women. Am J Pathol. 2014; 184(4): 1219–1229.
- Yang J, Liu X, Bhalla K, et al. Prevention of apoptosis by Bcl-2: release of cytochrome c from mitochondria blocked. Science. 1997; 275(5303): 1129–1132.
- Nam E, Lee SN, Im SA, et al. Expression of cyclooxygenase-2 in human breast cancer: relationship with HER-2/neu and other clinicopathological prognostic factors. Cancer Res Treat. 2005; 37(3): 165–170.
- van Slooten HJ, Clahsen PC, van Dierendonck JH, et al. Expression of Bcl-2 in node-negative breast cancer is associated with various prognostic factors, but does not predict response to one course of perioperative chemotherapy. Br J Cancer. 1996; 74(1): 78–85.
- Qiu JD, Xue XY, Li R, et al. Comparison of Clinicopathological Features and Prognosis in Triple-Negative and Non-Triple Negative Breast Cancer. J Cancer. 2016; 7(2): 167–173.
- Rakha EA, El-Sayed ME, Green AR, et al. Prognostic markers in triple-negative breast cancer. Cancer. 2007; 109(1): 25–32.
- van Nes JGH, de Kruijf EM, Faratian D, et al. COX2 expression in prognosis and in prediction to endocrine therapy in early breast cancer patients. Breast Cancer Res Treat. 2011; 125(3): 671–685.
- Kim T, Han W, Kim MK, et al. Predictive Significance of p53, Ki-67, and Bcl-2 Expression for Pathologic Complete Response after Neoadjuvant Chemotherapy for Triple-Negative Breast Cancer. J Breast Cancer. 2015; 18(1): 16–21.
- Ozretic P, Alvir I, Sarcevic B, et al. Apoptosis regulator Bcl-2 is an independent prognostic marker for worse overall survival in triple-negative breast cancer patients. Int J Biol Markers. 2018; 33(1): 109–115.
- Xu F, Li M, Zhang C, et al. Clinicopathological and prognostic significance of COX-2 immunohistochemical expression in breast cancer: a meta-analysis. Oncotarget. 2017; 8(4): 6003–6012.
- Krishnamachary B, Stasinopoulos I, Kakkad S, et al. Breast cancer cell cyclooxygenase-2 expression alters extracellular matrix structure and function and numbers of cancer associated fibroblasts. Oncotarget. 2017; 8(11): 17981–17994.
- Kakkad SM, Solaiyappan M, Argani P, et al. Collagen I fiber density increases in lymph node positive breast cancers: pilot study. J Biomed Opt. 2012; 17(11): 116017.
- Chikman B, Vasyanovich S, Lavy R, et al. COX2 expression in high-grade breast cancer: evidence for prognostic significance in the subset of triple-negative breast cancer patients. Med Oncol. 2014; 31(6): 989.
- Mosalpuria K, Hall C, Krishnamurthy S, et al. Cyclooxygenase-2 expression in non-metastatic triple-negative breast cancer patients. Mol Clin Oncol. 2014; 2(5): 845–850.
- Zhou L, Li Ke, Luo Y, et al. Novel prognostic markers for patients with triple-negative breast cancer. Hum Pathol. 2013; 44(10): 2180–2187.
- Basudhar D, Glynn SA, Greer M, et al. Coexpression of NOS2 and COX2 accelerates tumor growth and reduces survival in estrogen receptor-negative breast cancer. Proc Natl Acad Sci U S A. 2017; 114(49): 13030–13035.
- Ristimäki A, Sivula A, Lundin J, et al. Prognostic significance of elevated cyclooxygenase-2 expression in breast cancer. Cancer Res. 2002; 62(3): 632–635.
- Dings PJM, Elferink MAG, Strobbe LJA, et al. The prognostic value of lymph node ratio in node-positive breast cancer: a Dutch nationwide population-based study. Ann Surg Oncol. 2013; 20(8): 2607–2614.
- Simonsson M, Björner S, Markkula A, et al. The prognostic impact of COX-2 expression in breast cancer depends on oral contraceptive history, preoperative NSAID use, and tumor size. Int J Cancer. 2017; 140(1): 163–175.
- Beroukhim R, Mermel CH, Porter D, et al. The landscape of somatic copy-number alteration across human cancers. Nature. 2010; 463(7283): 899–905.
- Ayadi EZ, Cherif B, Ben Hamed Y, et al. Prognostic Value of BCL2 in Women Patients with Invasive Breast Cancer. Asian Pac J Cancer Prev. 2018; 19(12): 3557–3564.
- Callagy GM, Pharoah PD, Pinder SE, et al. Bcl-2 is a prognostic marker in breast cancer independently of the Nottingham Prognostic Index. Clin Cancer Res. 2006; 12(8): 2468–2475.
- Sezgin Alikanoglu A, Yildirim M, Suren D, et al. Expression of cyclooxygenase-2 and Bcl-2 in breast cancer and their relationship with triple-negative disease. J BUON. 2014; 19(2): 430–434.
- Escórcio-Dourado CS, Martins LM, Simplício-Revoredo CM, et al. Bcl-2 antigen expression in luminal A and triple-negative breast cancer. Med Oncol. 2017; 34(9): 161.
- Abdel-Fatah TMA, Perry C, Dickinson P, et al. Bcl2 is an independent prognostic marker of triple negative breast cancer (TNBC) and predicts response to anthracycline combination (ATC) chemotherapy (CT) in adjuvant and neoadjuvant settings. Ann Oncol. 2013; 24(11): 2801–2807.
- Abd El-Hafez A, Shawky Mohamed AEA, Elesawy BH. Different prognostic factors correlate with Bcl-2 expression among triple negative and non-triple negative breast cancers. Asian Pac J Cancer Prev. 2013; 14(2): 1037–1041.
- Sicking I, Rommens K, Battista MJ, et al. Prognostic influence of cyclooxygenase-2 protein and mRNA expression in node-negative breast cancer patients. BMC Cancer. 2014; 14: 952.
- Honma N, Horii R, Ito Y, et al. Differences in clinical importance of Bcl-2 in breast cancer according to hormone receptors status or adjuvant endocrine therapy. BMC Cancer. 2015; 15: 698.
- Lee KH, Im SA, Oh DY, et al. Prognostic significance of bcl-2 expression in stage III breast cancer patients who had received doxorubicin and cyclophosphamide followed by paclitaxel as adjuvant chemotherapy. BMC Cancer. 2007; 7: 63.
- Brzozowa-Zasada M, Kurek J, Piecuch A, et al. Correlation study of GAPDH, Bcl-2, and Bax protein immunoexpression in patients with colorectal adenocarcinoma. Prz Gastroenterol. 2018; 13(4): 322–331.
- Solanki R, Agrawal N, Ansari M, et al. COX-2 Expression in Breast Carcinoma with Correlation to Clinicopathological Parameters. Asian Pac J Cancer Prev. 2018; 19(7): 1971–1975.