Research Article
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Year 2022, Volume: 4 Issue: 4, 163 - 173, 29.10.2022
https://doi.org/10.46310/tjim.1090713

Abstract

References

  • Güneş ME, Çelik G, Trabulus FD, Aksoy Ş, Özoran E, Aren A, Gücin Z, Bahadır F. Üçlü (ER, PGR, HER2) negatif 47 meme kanserli hastanın değerlendirilmesi. Istanbul Tıp Dergisi (Istanbul Med J). 2012;13(4):166-8 (in Turkish). doi: 10.5505/1304.8503.2012.96158.
  • Dydensborg AB, Rose AA, Wilson BJ, Grote D, Paquet M, Giguère V, Siegel PM, Bouchard M. GATA3 inhibits breast cancer growth and pulmonary breast cancer metastasis. Oncogene. 2009 Jul 23;28(29):2634-42. doi: 10.1038/onc.2009.126.
  • Tozbikian GH, Zynger DL. A combination of GATA3 and SOX10 is useful for the diagnosis of metastatic triple-negative breast cancer. Hum Pathol. 2019 Mar;85:221-7. doi: 10.1016/j.humpath.2018.11.005.
  • Chou J, Provot S, Werb Z. GATA3 in development and cancer differentiation: cells GATA have it! J Cell Physiol. 2010 Jan;222(1):42-9. doi: 10.1002/jcp.21943.
  • Kouros-Mehr H, Slorach EM, Sternlicht MD, Werb Z. GATA-3 maintains the differentiation of the luminal cell fate in the mammary gland. Cell. 2006 Dec 1;127(5):1041-55. doi: 10.1016/j.cell.2006.09.048.
  • Yu S, Jiang X, Li J, Li C, Guo M, Ye F, Zhang M, Jiao Y, Guo B. Comprehensive analysis of the GATA transcription factor gene family in breast carcinoma using gene microarrays, online databases and integrated bioinformatics. Sci Rep. 2019 Mar 14;9(1):4467. doi: 10.1038/s41598-019-40811-3.
  • Takaku M, Grimm SA, Wade PA. GATA3 in breast cancer: Tumor suppressor or oncogene? Gene Expr. 2015;16(4):163-8. doi: 10.3727/105221615X14399878166113. 
  • Yoon NK, Maresh EL, Shen D, Elshimali Y, Apple S, Horvath S, Mah V, Bose S, Chia D, Chang HR, Goodglick L. Higher levels of GATA3 predict better survival in women with breast cancer. Hum Pathol. 2010 Dec;41(12):1794-801. doi: 10.1016/j.humpath.2010.06.010. 
  • Mehra R, Varambally S, Ding L, Shen R, Sabel MS, Ghosh D, Chinnaiyan AM, Kleer CG. Identification of GATA3 as a breast cancer prognostic marker by global gene expression meta-analysis. Cancer Res. 2005 Dec 15;65(24):11259-64. doi: 10.1158/0008-5472.CAN-05-2495.
  • Siegel RL, Miller KD, Jemal A. Cancer statistics, 2020. CA Cancer J Clin. 2020 Jan;70(1):7-30. doi: 10.3322/caac.21590.
  • Zheng R, Blobel GA. GATA Transcription factors and cancer. Genes Cancer. 2010 Dec;1(12):1178-88. doi: 10.1177/1947601911404223.
  • Wendroth SM, Mentrikoski MJ, Wick MR. GATA3 expression in morphologic subtypes of breast carcinoma: a comparison with gross cystic disease fluid protein 15 and mammaglobin. Ann Diagn Pathol. 2015 Feb;19(1):6-9. doi: 10.1016/j.anndiagpath.2014.12.001.
  • Miettinen M, McCue PA, Sarlomo-Rikala M, Rys J, Czapiewski P, Wazny K, Langfort R, Waloszczyk P, Biernat W, Lasota J, Wang Z. GATA3: a multispecific but potentially useful marker in surgical pathology: a systematic analysis of 2500 epithelial and nonepithelial tumors. Am J Surg Pathol. 2014 Jan;38(1):13-22. doi: 10.1097/PAS.0b013e3182a0218f.
  • Clark BZ, Beriwal S, Dabbs DJ, Bhargava R. Semiquantitative GATA-3 immunoreactivity in breast, bladder, gynecologic tract, and other cytokeratin 7-positive carcinomas. Am J Clin Pathol. 2014 Jul;142(1):64-71. doi: 10.1309/AJCP8H2VBDSCIOBF.
  • Liu H, Shi J, Wilkerson ML, Lin F. Immunohistochemical evaluation of GATA3 expression in tumors and normal tissues: a useful immunomarker for breast and urothelial carcinomas. Am J Clin Pathol. 2012 Jul;138(1):57-64. doi: 10.1309/AJCP5UAFMSA9ZQBZ.
  • Voduc D, Cheang M, Nielsen T. GATA-3 expression in breast cancer has a strong association with estrogen receptor but lacks independent prognostic value. Cancer Epidemiol Biomarkers Prev. 2008 Feb;17(2):365-73. doi: 10.1158/1055-9965.EPI-06-1090.
  • Gogia A, Raina V, Deo SV, Shukla NK, Mohanti BK. Triple-negative breast cancer: An institutional analysis. Indian J Cancer. 2014 Apr-Jun;51(2):163-6. doi: 10.4103/0019-509X.138275.
  • Vicente C, Conchillo A, García-Sánchez MA, Odero MD. The role of the GATA2 transcription factor in normal and malignant hematopoiesis. Crit Rev Oncol Hematol. 2012 Apr;82(1):1-17. doi: 10.1016/j.critrevonc.2011.04.007.
  • Bong PN, Zakaria Z, Muhammad R, Abdullah N, Ibrahim N, Emran NA, Syed Hussain SN. Expression and mutational analysis of GATA3 in Malaysian breast carcinomas. Malays J Pathol. 2010 Dec;32(2):117-22.
  • Graham K, Ge X, de Las Morenas A, Tripathi A, Rosenberg CL. Gene expression profiles of estrogen receptor-positive and estrogen receptor-negative breast cancers are detectable in histologically normal breast epithelium. Clin Cancer Res. 2011 Jan 15;17(2):236-46. doi: 10.1158/1078-0432.CCR-10-1369.
  • Fang SH, Chen Y, Weigel RJ. GATA-3 as a marker of hormone response in breast cancer. J Surg Res. 2009 Dec;157(2):290-5. doi: 10.1016/j.jss.2008.07.015.
  • Hosoda M, Yamamoto M, Nakano K, Hatanaka KC, Takakuwa E, Hatanaka Y, Matsuno Y, Yamashita H. Differential expression of progesterone receptor, FOXA1, GATA3, and p53 between pre- and postmenopausal women with estrogen receptor-positive breast cancer. Breast Cancer Res Treat. 2014 Apr;144(2):249-61. doi: 10.1007/s10549-014-2867-0.
  • Liu H, Shi J, Prichard JW, Gong Y, Lin F. Immunohistochemical evaluation of GATA-3 expression in ER-negative breast carcinomas. Am J Clin Pathol. 2014 May;141(5):648-55. doi: 10.1309/AJCP0Q9UQTEESLHN.
  • Albergaria A, Paredes J, Sousa B, Milanezi F, Carneiro V, Bastos J, Costa S, Vieira D, Lopes N, Lam EW, Lunet N, Schmitt F. Expression of FOXA1 and GATA-3 in breast cancer: the prognostic significance in hormone receptor-negative tumours. Breast Cancer Res. 2009;11(3):R40. doi: 10.1186/bcr2327. 
  • Lakhani SR. Ellis İO, Schnitt SJ, Tan PH, Vijyer MJ. Lyon. Invazive breast carcinoma: introduction and general feauture. In: World Health Organition Classification of Tumours of the Breast, 4th ed. IARC Press; 2012:13-31.
  • Usary J, Llaca V, Karaca G, Presswala S, Karaca M, He X, Langerød A, Kåresen R, Oh DS, Dressler LG, Lønning PE, Strausberg RL, Chanock S, Børresen-Dale AL, Perou CM. Mutation of GATA3 in human breast tumors. Oncogene. 2004 Oct 7;23(46):7669-78. doi: 10.1038/sj.onc.1207966. 
  • Clayton F. Pathologic correlates of survival in 378 lymph node-negative infiltrating ductal breast carcinomas. Mitotic count is the best single predictor. Cancer. 1991 Sep 15;68(6):1309-17. doi: 10.1002/1097-0142(19910915)68:6<1309::aid-cncr2820680621>3.0.co;2-i.
  • Toy H, Güngör S. Meme infiltratif duktal karsinomlarında histopatolojik grade ve proliferasyon belirleyicilerinin prognostik amaçlı kullanımı, Genel Tıp Dergisi. 2004;14(1):7-12 (in Turkish).
  • Ross JS, Fletcher JA. The HER-2/neu oncogene in breast cancer: Prognostic factor, predictive factor, and target for therapy. Oncologist. 1998;3(4):237-52.
  • Nederend J, Duijm LE, Voogd AC, Groenewoud JH, Jansen FH, Louwman MW. Trends in incidence and detection of advanced breast cancer at biennial screening mammography in the Netherlands: a population based study. Breast Cancer Res. 2012 Jan 9;14(1):R10. doi: 10.1186/bcr3091.
  • Yan W, Cao QJ, Arenas RB, Bentley B, Shao R. GATA3 inhibits breast cancer metastasis through the reversal of epithelial-mesenchymal transition. J Biol Chem. 2010 Apr 30;285(18):14042-51. doi: 10.1074/jbc.M110.105262.
  • Gonzalez RS, Wang J, Kraus T, Sullivan H, Adams AL, Cohen C. GATA-3 expression in male and female breast cancers: comparison of clinicopathologic parameters and prognostic relevance. Hum Pathol. 2013 Jun;44(6):1065-70. doi: 10.1016/j.humpath.2012.09.010.
  • Mohammed RA, Ellis IO, Lee AH, Martin SG. Vascular invasion in breast cancer; an overview of recent prognostic developments and molecular pathophysiological mechanisms. Histopathology. 2009 Jul;55(1):1-9. doi: 10.1111/j.1365-2559.2008.03169.x.
  • Jacquemier J, Charafe-Jauffret E, Monville F, Esterni B, Extra JM, Houvenaeghel G, Xerri L, Bertucci F, Birnbaum D. Association of GATA3, P53, Ki67 status and vascular peritumoral invasion are strongly prognostic in luminal breast cancer. Breast Cancer Res. 2009;11(2):R23. doi: 10.1186/bcr2249.
  • Asselin-Labat ML, Sutherland KD, Vaillant F, Gyorki DE, Wu D, Holroyd S, Breslin K, Ward T, Shi W, Bath ML, Deb S, Fox SB, Smyth GK, Lindeman GJ, Visvader JE. Gata-3 negatively regulates the tumor-initiating capacity of mammary luminal progenitor cells and targets the putative tumor suppressor caspase-14. Mol Cell Biol. 2011 Nov;31(22):4609-22. doi: 10.1128/MCB.05766-11.
  • Ni YB, Tsang JY, Chan SK, Tse GM. GATA-binding protein 3, gross cystic disease fluid protein-15 and mammaglobin have distinct prognostic implications in different invasive breast carcinoma subgroups. Histopathology. 2015 Jul;67(1):96-105. doi: 10.1111/his.12625.
  • Biserni GB, Di Oto E, Moskovszky LE, Foschini MP, Varga Z. Preferential expression of NY-BR-1 and GATA-3 in male breast cancer. J Cancer Res Clin Oncol. 2018 Feb;144(2):199-204. doi: 10.1007/s00432-017-2542-z.

Comparison of the expression of GATA-3 protein from the transcription factor family and pathological prognostic parameters in invasive ductal carcinomas of the breast

Year 2022, Volume: 4 Issue: 4, 163 - 173, 29.10.2022
https://doi.org/10.46310/tjim.1090713

Abstract

Background GATA binding protein 3 (GATA-3) is one of the six transcription factor family members and is important for glandular development in the breast. Its expression becomes important in breast cancer. We aimed to compare GATA-3 immunoreactivity and pathological prognostic factors in patients with invasive ductal carcinoma.
Material and Methods Our study was conducted retrospectively with 300 breast invasive ductal carcinoma patients who were operated on in our hospital between May 2013 and June 2014. Patient reports, slides and blocks in the pathology archive were scanned. GATA-3 immunohistochemical (IHC) staining was evaluated according to the nuclear staining, intensity and percentage. The relationship between clinicopathological prognostic parameters and GATA-3 IHC staining results was investigated.
Results A positive staining was observed in 286 (95.3%) cases. According to the GATA-3 staining intensity and percentage, 210 (70%) cases stained strongly and 246 (82%) stained +4, respectively. There was a significant relationship between GATA-3 immunoreactivity with ER, PR, Cerb-B2, Ki-67, mitotic degree, mitotic count and histological grade.
Conclusions There was a correlation between the high expression of GATA-3 and good prognostic markers. Hormone receptors can be evaluated with Cerb-B2 and Ki-67 and used as prognosis determinants in breast cancers. They can be used to identify both primary and secondary breast tumors.

References

  • Güneş ME, Çelik G, Trabulus FD, Aksoy Ş, Özoran E, Aren A, Gücin Z, Bahadır F. Üçlü (ER, PGR, HER2) negatif 47 meme kanserli hastanın değerlendirilmesi. Istanbul Tıp Dergisi (Istanbul Med J). 2012;13(4):166-8 (in Turkish). doi: 10.5505/1304.8503.2012.96158.
  • Dydensborg AB, Rose AA, Wilson BJ, Grote D, Paquet M, Giguère V, Siegel PM, Bouchard M. GATA3 inhibits breast cancer growth and pulmonary breast cancer metastasis. Oncogene. 2009 Jul 23;28(29):2634-42. doi: 10.1038/onc.2009.126.
  • Tozbikian GH, Zynger DL. A combination of GATA3 and SOX10 is useful for the diagnosis of metastatic triple-negative breast cancer. Hum Pathol. 2019 Mar;85:221-7. doi: 10.1016/j.humpath.2018.11.005.
  • Chou J, Provot S, Werb Z. GATA3 in development and cancer differentiation: cells GATA have it! J Cell Physiol. 2010 Jan;222(1):42-9. doi: 10.1002/jcp.21943.
  • Kouros-Mehr H, Slorach EM, Sternlicht MD, Werb Z. GATA-3 maintains the differentiation of the luminal cell fate in the mammary gland. Cell. 2006 Dec 1;127(5):1041-55. doi: 10.1016/j.cell.2006.09.048.
  • Yu S, Jiang X, Li J, Li C, Guo M, Ye F, Zhang M, Jiao Y, Guo B. Comprehensive analysis of the GATA transcription factor gene family in breast carcinoma using gene microarrays, online databases and integrated bioinformatics. Sci Rep. 2019 Mar 14;9(1):4467. doi: 10.1038/s41598-019-40811-3.
  • Takaku M, Grimm SA, Wade PA. GATA3 in breast cancer: Tumor suppressor or oncogene? Gene Expr. 2015;16(4):163-8. doi: 10.3727/105221615X14399878166113. 
  • Yoon NK, Maresh EL, Shen D, Elshimali Y, Apple S, Horvath S, Mah V, Bose S, Chia D, Chang HR, Goodglick L. Higher levels of GATA3 predict better survival in women with breast cancer. Hum Pathol. 2010 Dec;41(12):1794-801. doi: 10.1016/j.humpath.2010.06.010. 
  • Mehra R, Varambally S, Ding L, Shen R, Sabel MS, Ghosh D, Chinnaiyan AM, Kleer CG. Identification of GATA3 as a breast cancer prognostic marker by global gene expression meta-analysis. Cancer Res. 2005 Dec 15;65(24):11259-64. doi: 10.1158/0008-5472.CAN-05-2495.
  • Siegel RL, Miller KD, Jemal A. Cancer statistics, 2020. CA Cancer J Clin. 2020 Jan;70(1):7-30. doi: 10.3322/caac.21590.
  • Zheng R, Blobel GA. GATA Transcription factors and cancer. Genes Cancer. 2010 Dec;1(12):1178-88. doi: 10.1177/1947601911404223.
  • Wendroth SM, Mentrikoski MJ, Wick MR. GATA3 expression in morphologic subtypes of breast carcinoma: a comparison with gross cystic disease fluid protein 15 and mammaglobin. Ann Diagn Pathol. 2015 Feb;19(1):6-9. doi: 10.1016/j.anndiagpath.2014.12.001.
  • Miettinen M, McCue PA, Sarlomo-Rikala M, Rys J, Czapiewski P, Wazny K, Langfort R, Waloszczyk P, Biernat W, Lasota J, Wang Z. GATA3: a multispecific but potentially useful marker in surgical pathology: a systematic analysis of 2500 epithelial and nonepithelial tumors. Am J Surg Pathol. 2014 Jan;38(1):13-22. doi: 10.1097/PAS.0b013e3182a0218f.
  • Clark BZ, Beriwal S, Dabbs DJ, Bhargava R. Semiquantitative GATA-3 immunoreactivity in breast, bladder, gynecologic tract, and other cytokeratin 7-positive carcinomas. Am J Clin Pathol. 2014 Jul;142(1):64-71. doi: 10.1309/AJCP8H2VBDSCIOBF.
  • Liu H, Shi J, Wilkerson ML, Lin F. Immunohistochemical evaluation of GATA3 expression in tumors and normal tissues: a useful immunomarker for breast and urothelial carcinomas. Am J Clin Pathol. 2012 Jul;138(1):57-64. doi: 10.1309/AJCP5UAFMSA9ZQBZ.
  • Voduc D, Cheang M, Nielsen T. GATA-3 expression in breast cancer has a strong association with estrogen receptor but lacks independent prognostic value. Cancer Epidemiol Biomarkers Prev. 2008 Feb;17(2):365-73. doi: 10.1158/1055-9965.EPI-06-1090.
  • Gogia A, Raina V, Deo SV, Shukla NK, Mohanti BK. Triple-negative breast cancer: An institutional analysis. Indian J Cancer. 2014 Apr-Jun;51(2):163-6. doi: 10.4103/0019-509X.138275.
  • Vicente C, Conchillo A, García-Sánchez MA, Odero MD. The role of the GATA2 transcription factor in normal and malignant hematopoiesis. Crit Rev Oncol Hematol. 2012 Apr;82(1):1-17. doi: 10.1016/j.critrevonc.2011.04.007.
  • Bong PN, Zakaria Z, Muhammad R, Abdullah N, Ibrahim N, Emran NA, Syed Hussain SN. Expression and mutational analysis of GATA3 in Malaysian breast carcinomas. Malays J Pathol. 2010 Dec;32(2):117-22.
  • Graham K, Ge X, de Las Morenas A, Tripathi A, Rosenberg CL. Gene expression profiles of estrogen receptor-positive and estrogen receptor-negative breast cancers are detectable in histologically normal breast epithelium. Clin Cancer Res. 2011 Jan 15;17(2):236-46. doi: 10.1158/1078-0432.CCR-10-1369.
  • Fang SH, Chen Y, Weigel RJ. GATA-3 as a marker of hormone response in breast cancer. J Surg Res. 2009 Dec;157(2):290-5. doi: 10.1016/j.jss.2008.07.015.
  • Hosoda M, Yamamoto M, Nakano K, Hatanaka KC, Takakuwa E, Hatanaka Y, Matsuno Y, Yamashita H. Differential expression of progesterone receptor, FOXA1, GATA3, and p53 between pre- and postmenopausal women with estrogen receptor-positive breast cancer. Breast Cancer Res Treat. 2014 Apr;144(2):249-61. doi: 10.1007/s10549-014-2867-0.
  • Liu H, Shi J, Prichard JW, Gong Y, Lin F. Immunohistochemical evaluation of GATA-3 expression in ER-negative breast carcinomas. Am J Clin Pathol. 2014 May;141(5):648-55. doi: 10.1309/AJCP0Q9UQTEESLHN.
  • Albergaria A, Paredes J, Sousa B, Milanezi F, Carneiro V, Bastos J, Costa S, Vieira D, Lopes N, Lam EW, Lunet N, Schmitt F. Expression of FOXA1 and GATA-3 in breast cancer: the prognostic significance in hormone receptor-negative tumours. Breast Cancer Res. 2009;11(3):R40. doi: 10.1186/bcr2327. 
  • Lakhani SR. Ellis İO, Schnitt SJ, Tan PH, Vijyer MJ. Lyon. Invazive breast carcinoma: introduction and general feauture. In: World Health Organition Classification of Tumours of the Breast, 4th ed. IARC Press; 2012:13-31.
  • Usary J, Llaca V, Karaca G, Presswala S, Karaca M, He X, Langerød A, Kåresen R, Oh DS, Dressler LG, Lønning PE, Strausberg RL, Chanock S, Børresen-Dale AL, Perou CM. Mutation of GATA3 in human breast tumors. Oncogene. 2004 Oct 7;23(46):7669-78. doi: 10.1038/sj.onc.1207966. 
  • Clayton F. Pathologic correlates of survival in 378 lymph node-negative infiltrating ductal breast carcinomas. Mitotic count is the best single predictor. Cancer. 1991 Sep 15;68(6):1309-17. doi: 10.1002/1097-0142(19910915)68:6<1309::aid-cncr2820680621>3.0.co;2-i.
  • Toy H, Güngör S. Meme infiltratif duktal karsinomlarında histopatolojik grade ve proliferasyon belirleyicilerinin prognostik amaçlı kullanımı, Genel Tıp Dergisi. 2004;14(1):7-12 (in Turkish).
  • Ross JS, Fletcher JA. The HER-2/neu oncogene in breast cancer: Prognostic factor, predictive factor, and target for therapy. Oncologist. 1998;3(4):237-52.
  • Nederend J, Duijm LE, Voogd AC, Groenewoud JH, Jansen FH, Louwman MW. Trends in incidence and detection of advanced breast cancer at biennial screening mammography in the Netherlands: a population based study. Breast Cancer Res. 2012 Jan 9;14(1):R10. doi: 10.1186/bcr3091.
  • Yan W, Cao QJ, Arenas RB, Bentley B, Shao R. GATA3 inhibits breast cancer metastasis through the reversal of epithelial-mesenchymal transition. J Biol Chem. 2010 Apr 30;285(18):14042-51. doi: 10.1074/jbc.M110.105262.
  • Gonzalez RS, Wang J, Kraus T, Sullivan H, Adams AL, Cohen C. GATA-3 expression in male and female breast cancers: comparison of clinicopathologic parameters and prognostic relevance. Hum Pathol. 2013 Jun;44(6):1065-70. doi: 10.1016/j.humpath.2012.09.010.
  • Mohammed RA, Ellis IO, Lee AH, Martin SG. Vascular invasion in breast cancer; an overview of recent prognostic developments and molecular pathophysiological mechanisms. Histopathology. 2009 Jul;55(1):1-9. doi: 10.1111/j.1365-2559.2008.03169.x.
  • Jacquemier J, Charafe-Jauffret E, Monville F, Esterni B, Extra JM, Houvenaeghel G, Xerri L, Bertucci F, Birnbaum D. Association of GATA3, P53, Ki67 status and vascular peritumoral invasion are strongly prognostic in luminal breast cancer. Breast Cancer Res. 2009;11(2):R23. doi: 10.1186/bcr2249.
  • Asselin-Labat ML, Sutherland KD, Vaillant F, Gyorki DE, Wu D, Holroyd S, Breslin K, Ward T, Shi W, Bath ML, Deb S, Fox SB, Smyth GK, Lindeman GJ, Visvader JE. Gata-3 negatively regulates the tumor-initiating capacity of mammary luminal progenitor cells and targets the putative tumor suppressor caspase-14. Mol Cell Biol. 2011 Nov;31(22):4609-22. doi: 10.1128/MCB.05766-11.
  • Ni YB, Tsang JY, Chan SK, Tse GM. GATA-binding protein 3, gross cystic disease fluid protein-15 and mammaglobin have distinct prognostic implications in different invasive breast carcinoma subgroups. Histopathology. 2015 Jul;67(1):96-105. doi: 10.1111/his.12625.
  • Biserni GB, Di Oto E, Moskovszky LE, Foschini MP, Varga Z. Preferential expression of NY-BR-1 and GATA-3 in male breast cancer. J Cancer Res Clin Oncol. 2018 Feb;144(2):199-204. doi: 10.1007/s00432-017-2542-z.
There are 37 citations in total.

Details

Primary Language English
Subjects ​Internal Diseases
Journal Section Original Articles
Authors

Leymune Parlak 0000-0002-5503-3067

Olcay Kandemir 0000-0002-5293-7837

Publication Date October 29, 2022
Submission Date March 23, 2022
Acceptance Date April 26, 2022
Published in Issue Year 2022 Volume: 4 Issue: 4

Cite

EndNote Parlak L, Kandemir O (October 1, 2022) Comparison of the expression of GATA-3 protein from the transcription factor family and pathological prognostic parameters in invasive ductal carcinomas of the breast. Turkish Journal of Internal Medicine 4 4 163–173.

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