Skip to main content

Advertisement

SpringerLink
Log in

GATA-3 is superior to GCDFP-15 and mammaglobin to identify primary and metastatic breast cancer

  • Preclinical study
  • Published:
Breast Cancer Research and Treatment Aims and scope Submit manuscript

Abstract

Purpose

Despite numerous studies on the utility of GATA-3 as breast cancer marker, its comparison with other breast markers, its concordance between primary and metastatic tumors and its expression in primary cancers from sites with frequent breast metastases remains unclear.

Methods

To address these questions, totally 993 invasive breast cancers (IBC), 254 paired nodal metastases, 23 distant metastases, and 208 lung carcinomas were included. GATA-3 expression was analyzed by immunohistochemistry and compared to other breast markers [gross cystic disease fluid protein 15 (GCDFP-15) and mammaglobin (MGB)].

Results

GATA-3 was expressed in 82.5% of IBC, predominantly in luminal (93.9%), and lower in non-luminal cancers [59.6% of HER2 overexpressing (HER2-OE) and 38.1% of triple negative breast cancer (TNBC) subtypes]. GATA-3 identified more IBC than GCDFP-15 (23.9%) and MGB (46.6%). However, MGB showed a comparable sensitivity for non-luminal cancers to GATA-3. Combining MGB and GATA-3 improved sensitivity for both HER2-OE (80.8%) and TNBC cases (55.4%). GATA-3 showed a high sensitivity for nodal metastases and distant metastases, with good concordance with primary tumors. GATA-3 was expressed in 1.0% of lung carcinomas, with sensitivity and specificity of 82.5 and 99.0% in differentiating IBC and lung carcinoma.

Conclusions

GATA-3 expression was the highest in luminal breast carcinomas, and showed higher sensitivity than GCDFP-15 and MGB. However, in the poorly differentiated IBC, its utility was still limited. One should be aware of the possible GATA-3 expression in lung carcinomas.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Similar content being viewed by others

References

  1. Labastie MC, Bories D, Chabret C, Grégoire JM, Chrétien S, Roméo PH (1994) Structure and expression of the human GATA3 gene. Genomics 21:1–6

    Article  CAS  PubMed  Google Scholar 

  2. Chou J, Provot S, Werb Z (2010) GATA3 in development and cancer differentiation: cells GATA have it! J Cell Physiol 222:42–49

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  3. Zheng R, Blobel G (2010) GATA transcription factors and cancer. Genes Cancer 1:1178–1188

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  4. Yagi R, Zhu J, Paul WE (2011) An updated view on transcription factor GATA3-mediated regulation of Th1 and Th2 cell differentiation. Int Immunol 23:415–420

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  5. Oosterwegel M, Timmerman J, Leiden J, Clevers H (1992) Expression of GATA-3 during lymphocyte differentiation and mouse embryogenesis. Dev Immunol 3:1–11

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  6. Yoon NK, Maresh EL, Shen D, Elshimali Y, Apple S, Horvath S, Mah V, Bose S, Chia D, Chang HR, Goodglick L (2010) Higher levels of GATA3 predict better survival in women with breast cancer. Hum Pathol 41:1794–1801

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  7. Kouros-Mehr H, Slorach EM, Sternlicht MD, Werb Z (2006) GATA-3 maintains the differentiation of the luminal cell fate in the mammary gland. Cell 127:1041–1055

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  8. Asselin-Labat ML, Sutherland KD, Barker H, Thomas R, Shackleton M, Forrest NC, Hartley L, Robb L, Grosveld FG, vander Wees J, Lindeman GJ, Visvader JE (2007) Gata-3 is an essential regulator of mammary-gland morphogenesis and luminal-cell differentiation. Nat Cell Biol 19:201–209

    Article  Google Scholar 

  9. Ting CN, Olson MC, Barton KP, Leiden JM (1996) Transcription factor GATA-3 is required for development of the T-cell lineage. Nature 384:474–478

    Article  CAS  PubMed  Google Scholar 

  10. Naito T, Tanaka H, Naoe Y, Taniuchi I (2011) Transcriptional control of T-cell development. Int Immunol 23:661–668

    Article  CAS  PubMed  Google Scholar 

  11. Pai SY, Truitt ML, Ting CN, Leiden JM, Glimcher LH, Ho IC (2003) Critical roles for transcription factor GATA-3 in thymocyte development. Immunity 19:863–875

    Article  CAS  PubMed  Google Scholar 

  12. Hendriks RW, Nawijn MC, Engel JD, van Doorninck H, Grosveld F, Karis A (1999) Expression of the transcription factor GATA-3 is required for the development of the earliest T cell progenitors and correlates with stages of cellular proliferation in the thymus. Eur J Immunol 29:1912–1918

    Article  CAS  PubMed  Google Scholar 

  13. Tong Q, Dalgin G, Xu H, Ting CN, Leiden JM, Hotamisligil GS (2000) Function of GATA transcription factors in preadipocyte-adipocyte transition. Science 290:134–138

    Article  CAS  PubMed  Google Scholar 

  14. Grote D, Souabni A, Busslinger M, Bouchard M (2006) Pax2/8-regulated Gata 3 expression is necessary for morphogenesis and guidance of the nephric duct in the developing kidney. Development 133:53–61

    Article  CAS  PubMed  Google Scholar 

  15. Tsarovina K, Pattyn A, Stubbusch J, Müller F, van der Wees J, Schneider C, Brunet JF, Rohrer H (2004) Essential role of Gata transcription factors in sympathetic neuron development. Development 131:4775–4786

    Article  CAS  PubMed  Google Scholar 

  16. Kaufman CK, Zhou P, Pasolli HA, Rendl M, Bolotin D, Lim KC, Dai X, Alegre ML, Fuchs E (2003) GATA-3:an unexpected regulator of cell lineage determination in skin. Genes Dev 17:2108–2122

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  17. Liu H, Shi J, Wilkerson ML, Lin F (2012) Immunohistochemical evaluation of GATA-3 expression in tumors and normal tissues: a useful immunomarker for breast and urothelial carcinomas. Am J Clin Pathol 138:57–64

    Article  PubMed  Google Scholar 

  18. Ordóñez NG (2013) Value of GATA3 immunostaining in tumor diagnosis: a review. Adv Anat Pathol 20:352–360

    Article  PubMed  Google Scholar 

  19. Shield PW, Papadimos DJ, Walsh MD (2014) GATA3: a promising marker for metastatic breast carcinoma in serous effusion specimens. Cancer Cytopathol. https://doi.org/10.1002/cncy.21393

    PubMed  Google Scholar 

  20. Yang M, Nonaka D (2010) A study of immunohistochemical differential expression in pulmonary and mammary carcinomas. Mod Pathol 23:654–661

    Article  CAS  PubMed  Google Scholar 

  21. Asch-Kendrick R, Cimino-Mathews A (2016) The role of GATA3 in breast carcinomas: a review. Hum Pathol 48:37–47

    Article  CAS  PubMed  Google Scholar 

  22. Shaoxian T, Baohua Y, Xiaoli X, Yufan C, Xiaoyu T, Hongfen L, Rui B, Xiangjie S, Ruohong S, Wentao Y (2017) Characterisation of GATA3 expression in invasive breast cancer: differences in histological subtypes and immunohistochemically defined molecular subtypes. J Clin Pathol. https://doi.org/10.1136/jclinpath-2016-204137

    PubMed  Google Scholar 

  23. Huo L, Gong Y, Guo M, Gilcrease MZ, Wu Y, Zhang H, Zhang J, Resetkova E, Hunt KK, Deavers MT (2015) GATA-binding protein 3 enhances the utility of gross cystic disease fluid protein-15 and mammaglobin A in triple-negative breast cancer by immunohistochemistry. Histopathology 67(2):245–254

    Article  PubMed  Google Scholar 

  24. Yang Y, Lu S, Zeng W, Xie S, Xiao S (2017) GATA3 expression in clinically useful groups of breast carcinoma: a comparison with GCDFP15 and mammaglobin for identifying paired primary and metastatic tumors. Ann Diagn Pathol 26:1–5

    Article  PubMed  Google Scholar 

  25. Deftereos G, Sanguino Ramirez AM, Silverman JF, Krishnamurti U (2015) GATA3 immunohistochemistry expression in histologic subtypes of primary breast carcinoma and metastatic breast carcinoma cytology. Am J Surg Pathol 39(9):1282–1289

    Article  PubMed  Google Scholar 

  26. Braxton DR, Cohen C, Siddiqui MT (2015) Utility of GATA3 immunohistochemistry for diagnosis of metastatic breast carcinoma in cytology specimens. Diagn Cytopathol 43(4):271–277

    Article  PubMed  Google Scholar 

  27. Sangoi AR, Shrestha B, Yang G, Mego O, Beck AH (2016) The novel marker GATA3 is significantly more sensitive than traditional markers mammaglobin and GCDFP15 for identifying breast cancer in surgical and cytology specimens of metastatic and matched primary tumors. Appl Immunohistochem Mol Morphol 24(4):229–237

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  28. McShane LM, Altman DG, Sauerbrei W, Taube SE, Gion M, Clark GM (2006) REporting recommendations for tumor MARKer prognostic studies (REMARK). Breast Cancer Res Treat 100:229–235

    Article  PubMed  Google Scholar 

  29. Lakhani SR, Ellis IO, Schnitt SJ, Tan PH, Van de Vijver MJ (2012) WHO classification of tumours of the breast. Int Agency Res Cancer, Lyon

    Google Scholar 

  30. Elston CW, Ellis IO (1991) Pathological prognostic factors in breast cancer. I. The value of histological grade in breast cancer: experience from a large study with long-term follow-up. Histopathology 19:403–410

    Article  CAS  PubMed  Google Scholar 

  31. Edge SB, Byrd DR, Compton CC, Fritz AG, Greene FL, Trotti AM 3rd (2010) AJCC cancer staging manual, 7th edn. Springer, New York

    Google Scholar 

  32. Hammond ME, Hayes DF, Dowsett M, Allred DC, Hagerty KL, Badve S, Fitzgibbons PL, Francis G, Goldstein NS, Hayes M, Hicks DG, Lester S, Love R, Mangu PB, McShane L, Miller K, Osborne CK, Paik S, Perlmutter J, Rhodes A, Sasano H, Schwartz JN, Sweep FC, Taube S, Torlakovic EE, Valenstein P, Viale G, Visscher D, Wheeler T, Williams RB, Wittliff JL, Wolff AC (2010) American Society of Clinical Oncology/College of American Pathologists guideline recommendations for immunohistochemical testing of estrogen and progesterone receptors in breast cancer. J Clin Oncol 28:2784–2795

    Article  PubMed  PubMed Central  Google Scholar 

  33. Wolff AC, Hammond ME, Hicks DG, Dowsett M, McShane LM, Allison KH, Allred DC, Bartlett JM, Bilous M, Fitzgibbons P, Hanna W, Jenkins RB, Mangu PB, Paik S, Perez EA, Press MF, Spears PA, Vance GH, Viale G, Hayes DF, American Society of Clinical Oncology, College of American Pathologists (2013) 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. J Clin Oncol 31:3997–4013

    Article  Google Scholar 

  34. Curigliano G, Burstein HJ, Winer PE et al (2017) De-escalating and escalating treatments for early-stage breast cancer: the St. Gallen international expert consensus conference on the primary therapy of early breast cancer. Ann Oncol 28(8):1700–1712

    CAS  PubMed  Google Scholar 

  35. Ni YB, Tsang JY, Shao MM, Chan SK, Tong J, To KF, Tse GM (2014) TTF-1 expression in breast carcinoma: an unusual but real phenomenon. Histopathology 64:504–511

    Article  PubMed  Google Scholar 

  36. Miettinen M, McCue PA, Sarlomo-Rikala M, Rys J, Czapiewski P, Wazny K, Langfort R, Waloszczyk P, Biernat W, Lasota J, Wang Z (2014) GATA3: a multispecific but potentially useful marker in surgical pathology: a systematic analysis of 2500 epithelial and nonepithelial tumors. Am J Surg Pathol 38:13–22

    Article  PubMed  PubMed Central  Google Scholar 

  37. Gonzalez RS, Wang J, Kraus T, Sullivan H, Adams AL, Cohen C (2013) GATA-3 expression in male and female breast cancers: comparison of clinicopathologic parameters and prognostic relevance. Hum Pathol 44(6):1065–1070

    Article  CAS  PubMed  Google Scholar 

  38. Min KW, Kim DH, Do SI, Chae SW, Kim K, Sohn JH, Lee HJ, Do IG, Pyo JS, Kim Y, Kim DH, Yang JH, Lee SJ, Oh YH, Oh S, Choi SH, Park YL, Park CH, Kim EK, Kwon MJ, Seo J (2017) Expression pattern of Smad4/GATA3 as a predictor of survival in invasive ductal carcinoma of the breast. Pathobiology 84(3):130–138

    Article  CAS  PubMed  Google Scholar 

  39. Perou CM, Sørlie T, Eisen MB, van de Rijn M, Jeffrey SS, Rees CA, Pollack JR, Ross DT, Johnsen H, Akslen LA, Fluge O, Pergamenschikov A, Williams C, Zhu SX, Lønning PE, Børresen-Dale AL, Brown PO, Botstein D (2000) Molecular portraits of human breast tumours. Nature 406:747–752

    Article  CAS  PubMed  Google Scholar 

  40. Tominaga N, Naoi Y, Shimazu K, Nakayama T, Maruyama N, Shimomura A, Kim SJ, Tamaki Y, Noguchi S (2012) Clinicopathological analysis of GATA3-positive breast cancers with special reference to response to neoadjuvant chemotherapy. Ann Oncol 23(12):3051–3057

    Article  CAS  PubMed  Google Scholar 

  41. Cakir A, Isik Gonul I, Ekinci O, Cetin B, Benekli M, Uluoglu O (2017) GATA3 expression and its relationship with clinicopathological parameters in invasive breast carcinomas. Pathol Res Pract 213(3):227–234

    Article  CAS  PubMed  Google Scholar 

  42. Chu IM, Michalowski AM, Hoenerhoff M, Szauter KM, Luger D, Sato M, Flanders K, Oshima A, Csiszar K, Green JE (2012) GATA3 inhibits lysyl oxidase-mediated metastases of human basal triple-negative breast cancer cells. Oncogene 31(16):2017–2027

    Article  CAS  PubMed  Google Scholar 

  43. Asch-Kendrick R, Cimino-Mathews A (2016) The role of GATA3 in breast carcinomas: a review. Hum Pathol 48:37–47

    Article  CAS  PubMed  Google Scholar 

  44. Liu H, Shi J, Prichard JW, Gong Y, Lin F (2014) Immunohistochemical evaluation of GATA-3 expression in ER-negative breast carcinomas. Am J Clin Pathol 141(5):648–655

    Article  PubMed  Google Scholar 

  45. Krings G, Nystrom M, Mehdi I, Vohra P, Chen YY (2014) Diagnostic utility and sensitivities of GATA3 antibodies in triple-negative breast cancer. Hum Pathol 45(11):2225–2232

    Article  CAS  PubMed  Google Scholar 

  46. Ni YB, Tsang JY, Chan SK, Tse GM (2015) GATA-binding protein 3, gross cystic disease fluid protein-15 and mammaglobin have distinct prognostic implications in different invasive breast carcinoma subgroups. Histopathology 67(1):96–105

    Article  PubMed  Google Scholar 

  47. Parikh P, Palazzo JP, Rose LJ, Daskalakis C, Weigel RJ (2005) GATA-3 expression as a predictor of hormone response in breast cancer. J Am Coll Surg 200(5):705–710

    Article  PubMed  Google Scholar 

  48. Wendroth SM, Mentrikoski MJ, Wick MR (2015) GATA3 expression in morphologic subtypes of breast carcinoma: a comparison with gross cystic disease fluid protein 15 and mammaglobin. Ann Diagn Pathol 19(1):6–9

    Article  PubMed  Google Scholar 

  49. Luo MH, Huang YH, Ni YB, Tsang JY, Chan SK, Shao MM, Tse GM (2013) Expression of mammaglobin and gross cystic disease fluid protein-15 in breast carcinomas. Hum Pathol 44:1241–1250

    Article  CAS  PubMed  Google Scholar 

  50. Cimino-Mathews A, Subhawong AP, Illei PB, Sharma R, Halushka MK, Vang R, Fetting JH, Park BH, Argani P (2013) GATA3 expression in breast carcinoma: utility in triple-negative, sarcomatoid, and metastatic carcinomas. Hum Pathol 44:1341–1349

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  51. Robens J, Goldstein L, Gown AM, Schnitt SJ (2010) Thyroid transcription factor-1 expression in breast carcinomas. Am J Surg Pathol 34:1881–1885

    Article  PubMed  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Department of Anatomical and Cellular Pathology, Prince of Wales Hospital, The Chinese University of Hong Kong, Ngan Shing Street, Shatin, NT, Hong Kong

    Yun-Bi Ni, Julia Y. S. Tsang, Joanna Tong, Ka-Fai To & Gary M. Tse

  2. Department of Pathology, Shenzhen Affiliated Hospital, Guangzhou University of Traditional Chinese Medicine, Shenzhen, China

    Mu-Min Shao

  3. Department of Pathology, Kwong Wah Hospital, Hong Kong, Hong Kong

    Siu-Ki Chan

  4. Department of Pathology, Tuen Mun Hospital, Hong Kong, Hong Kong

    Sai-Yin Cheung

Authors
  1. Yun-Bi Ni
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Julia Y. S. Tsang
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Mu-Min Shao
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Siu-Ki Chan
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Sai-Yin Cheung
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Joanna Tong
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. Ka-Fai To
    View author publications

    You can also search for this author in PubMed Google Scholar

  8. Gary M. Tse
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Gary M. Tse.

Ethics declarations

Conflicts of interest

The authors declare that they have no conflicts of interest.

Electronic supplementary material

Below is the link to the electronic supplementary material.

Supplementary material 1 (DOCX 4168 kb)

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Ni, YB., Tsang, J.Y.S., Shao, MM. et al. GATA-3 is superior to GCDFP-15 and mammaglobin to identify primary and metastatic breast cancer. Breast Cancer Res Treat 169, 25–32 (2018). https://doi.org/10.1007/s10549-017-4645-2

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s10549-017-4645-2

Keywords

Search

Navigation