Study of GATA-3 Expression in Breast Carcinoma in a Tertiary Care Hospital in Eastern India GATA3 expression in breast carcinoma

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Lahari Banik https://orcid.org/0000-0003-3950-3724
Mallika Pal https://orcid.org/0000-0003-3308-467X
Nabanita Mayur https://orcid.org/0000-0003-0824-2488

Keywords

breast carcinoma, GATA3, immunohistochemical marker

Abstract

Background: Transcription factor GATA3 is a relatively new and specific biomarker for breast carcinoma that regulates luminal cell differentiation. However, further studies that elucidate its role and diagnostic utility in breast cancer is desired. Therefore, this study was conducted to assess GATA3 expression in breast carcinoma and determine its association with various known prognostic and predictive factors of breast carcinoma.


Methods: This is a cross-sectional, observational study where 110 breast carcinoma cases were examined histologically on H&E stained slides for routine parameters such as tumor morphological type and histologic grade.ER/PR/Her-2-neu/ki67 and GATA3 expression was determined using immunohistochemistry. All cases were assessed to determine the association of GATA3 with different established clinicopathological parameters in breast cancer such as patient age, axillary lymph node status, tumor grade, lymphovascular invasion, molecular subtype etc. The results were statistically analyzed and P value < 0.05 was considered to be significant.


Results: 97 cases (88.1%) expressed GATA3 and it was significantly associated with most of the established clinico-pathological parameters like family history of breast cancer, tumour size and histology grade, lymph node and margin status, presence of lymphovascular invasion and carcinoma in-situ component .GATA3 expression was also significantly associated with ER/PR/Her2neu/ki67 expression.


Conclusion: GATA3 expression is significantly associated with the different established clinicopathological parameters of breast cancer. Therefore, it may be considered as a relevant marker more routinely. Further studies of GATA3 in breast cancer may refine prognostic models, predict clinical outcomes and modify treatment guidelines in future

References

1. Merika M, Stuart H. DNA-binding specificity of GATA family transcription factors. Mol Cell Biol 1993; 13:4011–4022. doi: 10.1128/MCB.13.7.3999.
2. Asselin-Labat ML, Sutherland KD, Barker H, Thomas R, Shackleton M, Forrest NC, et al. GATA-3 is an essential regulator of mammary-gland morphogenesis and luminal-cell differentiation. Nat Cell Biol 2007; 9:201–209. doi: 10.1038/ncb1530.
3. Sørlie T, Perou CM, Tibshirani R, Aas T, Geisler S, Johnsen H, et al. Gene expression patterns of breast carcinomas distinguish tumor subclasses with clinical implications. Proc Natl AcadSci U S A 2001;98:10869 – 74. doi: 10.1073/pnas.191367098.
4. Charafe-Jauffret E, Ginestier C, Monville F, Finetti P, Adélaïde J, Cervera N, et al. Gene expression profiling of breast cell lines identifies potential new basal markers. Oncogene 2006;25:2273 – 84. doi: 10.1038/sj.onc.1209254.
5. Mehra R, Varambally S, Ding L, Shen R, Sabel MS, Ghosh D, et al. Identification of GATA-3 as a breast cancer prognostic marker by global gene expression meta analysis. Cancer Res 2005;65:11259 – 64. doi: 10.1158/0008-5472.CAN-05-2495.
6. Usary J, Llaca V, Karaca G, Presswala S, Karaca M, He X, et al. Mutation of GATA-3 in human breast tumors. Oncogene. 2004;23:7669-7678. doi: 10.1038/sj.onc.1207966.
7. Arnold JM, Choong DY, Thompson ER; kConFab, Waddell N, Lindeman GJ, Visvader JE, et al. Frequent somatic mutations of GATA-3 in non-BRCA1/BRCA2 familial breast tumors, but not in BRCA1-, BRCA2- or sporadic breast tumors. Breast Cancer Res Treat. 2010;119:491-496. doi: 10.1007/s10549-008-0269-x.
8. Cimino-Mathews A, Subhawong AP, Illei PB, Sharma R, Halushka MK, Vang R, et al. GATA-3 expression in breast carcinoma: utility in triple-negative, sarcomatoid, and metastatic carcinomas. Hum Pathol. 2013;44:1341-1349. doi: 10.1016/j.humpath.2012.11.003.
9. Yoon NK, Maresh EL, Shen D, Elshimali Y, Apple S, Horvath S, et al. Higher levels of GATA-3 predict better survival in women with breast cancer. Hum Pathol. 2010 Dec;41(12):1794-801. doi: 10.1016/j.humpath.2010.06.010.
10. Lakhani SR, Ellis LO, Schnitt SJ, Tan PH, van de Vijver MJ. Tumors of the breast in World Health Organization classification of tumors. Pathology and genetics of tumors of breast and female genital organs. 4th ed. Lyon: IARC Press; 2012. p. 8.
11. Ellis IO, Reis-Filho JS, Simpson JF, Decker T. Invasive breast carcinoma: introduction and general features in World Health Organization classification of tumors. 4th ed. Lyon: IARC Press; 2012. p. 19.
12. Gujam FJ, Going JJ, Edwards J, Mohammed ZM, McMillan DC. The role of lymphatic and blood vessel invasion in predicting survival and methods of detection in patients with primary operable breast cancer. Crit Rev Oncol Hematol 2014; 89:231–241. doi: 10.1016/j.critrevonc.2013.08.014.
13. Allred DC. Problems and solutions in the evaluation of hormone receptors in breast cancer. J Clin Oncol. 2008;26(15):2433-2435. doi: 10.1200/JCO.2007.15.7800.
14. Wolff A, Hammond M, Hicks D, Dowsett M, McShane L, Allison K, et al. Recommendations for Human Epidermal Growth Factor Receptor 2 Testing in Breast Cancer: American Society of Clinical Oncology/College of American Pathologists Clinical Practice Guideline Update. Archives of Pathology & Laboratory Medicine. 2014;138:241-256. doi: 10.1200/JCO.2013.50.9984.
15. Goldhirsch A, Wood WC, Coates AS, Gelber RD, Thurlimann B, Senn HJ. Strategies for subtypes − dealing with the diversity of breast cancer: highlights of the St Gallen International Expert Consensus on the Primary Therapy of Early Breast Cancer. Ann Oncol 2013; 22:1736–1740. doi: 10.1093/annonc/mdr304.
16. Agarwal H, Babu S, Rana C, Kumar M, Singhai A, Shankhwar SN, et al. Diagnostic utility of GATA-3 immunohistochemical expression in urothelial carcinoma. Indian J Pathol Microbiol 2019;62:244-50. Available from: https://www.ijpmonline.org/text.asp?2019/62/2/244/255808
17. Ismail A, Khalifa S, Saied E, El-Tamamy M. Immunohistochemical study of GATA-3 expression versus estrogen and progesterone receptor in invasive mammary carcinomas. Kasr Al Ainy Medical Journal 2018, 24:40–46. Available from: http://www.kamj.eg.net/text.asp?2018/24/1/40/233107
18. Albergaria A, Paredes J, Sousa B, Milanezi F, Carneiro V, Bastos J, et al. Expression of FOXA1 and GATA-3 in breast cancer: the prognostic significance in hormone receptor-negative tumours. Breast Cancer Res 2009; 11:R40. doi: 10.1186/bcr2327.
19. David Voduc, Maggie Cheang, and Torsten Nielsen. GATA-3 Expression in Breast Cancer Has a Strong Association with Estrogen Receptor but Lacks Independent Prognostic Value. Cancer Epidemiol Biomarkers Prev 2008;17(2).February 2008. doi: 10.1158/1055-9965.EPI-06-1090.
20. Yan W, Cao QJ, Arenas RB, Bentley B, Shao R. GATA-3 inhibits breast cancer metastasis through the reversal of epithelial-mesenchymal transition. The Journal of biological chemistry, (2010). 285(18), 14042–14051. doi:10.1074/jbc.M110.105262.
21. Jiang YZ, Yu KD, Zuo WJ, Peng WT, Shao ZM. GATA-3 mutations define a unique subtype of luminal-like breast cancer with improved survival. Cancer 2014; 120:1329–1337. doi: 10.1002/cncr.28566.
22. Yildirim E, Bektas S, Gundogar O, Findik D, Alcicek S, Erdogan KO, et al. The Relationship of GATA-3 and Ki-67 With Histopathological Prognostic Parameters, Locoregional Recurrence and Disease-free Survival in Invasive Ductal Carcinoma of the Breast. Anticancer Research Oct 2020, 40 (10) 5649-5657; doi: 10.21873/anticanres.14578.

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