GATA-3 and FOXA1 expression is useful to differentiate breast carcinoma from other carcinomas

Our plain-English summary of GATA-3 and FOXA1 expression is useful to differentiate breast carcinoma from other carcinomas, by D.G. Davis, M.T. Siddiqui, G. Oprea-Ilies, et al (Human Pathology, 2016).

The study

• Authors: D.G. Davis, M.T. Siddiqui, G. Oprea-Ilies, K. Stevens, A.O. Osunkoya, C. Cohen, X.B. Li
• Journal: Human Pathology
• Published: 2016;47(1):26-31
• Cited by: 65 articles, as counted by NIH iCite
• Read it: PubMed · Publisher

Abstract

GATA-3, a member of the GATA family of zinc-finger DNA binding proteins, and FOXA1, a member of the forkhead transcription factor family, are both associated with estrogen receptor expression. Both GATA-3 and FOXA1 are useful markers for breast carcinoma, but their expression in the different breast cancer subtypes and other neoplasms has not been thoroughly evaluated. We examined the expression of GATA-3 and FOXA1 in estrogen receptor-positive, Her2/neu-positive, and triple-negative breast carcinomas as well as in 10 other common carcinomas, including hepatocellular, colonic, pancreatic, gastric, endometrial (endometrioid), lung, prostatic, renal cell, urothelial, and ovarian serous carcinomas. Primary and metastatic melanomas and mesotheliomas were also evaluated. GATA-3 and FOXA1 staining of estrogen receptor-positive breast carcinomas was seen in 96.6% and 96.2%, respectively. In triple-negative breast carcinomas, GATA-3 and FOXA1 staining was seen in 21.6% and 15.9%, respectively. Among the other tumors, GATA-3 staining was only seen in urothelial carcinoma (70.9%) and FOXA1 staining was only seen in prostatic (87.5%), urothelial (5.1%) carcinomas, and mesotheliomas (40.0%). In conclusion, GATA-3 and FOXA1 are excellent breast carcinoma markers; however, their utility is limited in the triple-negative subtype. The utility of FOXA1 in diagnosing prostatic carcinoma and mesothelioma warrants further investigation.

Copyright © 2015 Elsevier Inc. All rights reserved.

In plain English

This laboratory study from Emory University in Atlanta tested two tissue stains, GATA-3 and FOXA1, to see how well they distinguish breast cancer from other cancers. The authors stained archived tumor samples: three subtypes of breast cancer, ten other common carcinomas, 27 melanomas and 15 mesotheliomas (13 epithelioid, 1 biphasic, 1 sarcomatoid). The article does not report asbestos exposure or where in the body the mesotheliomas arose. GATA-3 stained 115 of 119 estrogen receptor-positive breast cancers but only 11 of 51 triple-negative ones. Among the other tumors it stained only urothelial carcinomas (56 of 79), and none of the mesotheliomas. FOXA1 stained 127 of 132 estrogen receptor-positive and 7 of 44 triple-negative breast cancers, 42 of 48 prostatic carcinomas, 4 of 75 urothelial carcinomas and 6 of 15 mesotheliomas. It stained no lung carcinomas. The authors concluded that both stains are excellent breast cancer markers but of limited use in triple-negative cancers. They said FOXA1's use for prostatic carcinoma and mesothelioma warrants further study, and they noted that their mesothelioma sample was small.

We wrote this plain-English summary from the full article with the help of AI, and a second AI model checked each sentence against the article. It is not the authors' wording; the abstract and the article are their own account.

What the study did and found

• Design: Laboratory (immunohistochemistry) study of archived tumor tissue, mostly using tissue microarrays
• Who was studied: Archived tumors from Emory University and Grady Memorial Hospitals (Atlanta), with no dates given. These were breast carcinomas (ER+/Her2−, Her2+, triple-negative) plus 100 hepatocellular, 81 colonic, 28 pancreatic, 31 gastric, 27 endometrial (endometrioid), 27 lung, 48 prostatic, 48 renal cell, 79 urothelial and 27 ovarian serous carcinomas, 27 melanomas, and 15 mesotheliomas (13 epithelioid, 1 biphasic, 1 sarcomatoid) on whole slide sections.
• Exposure: No asbestos or other environmental exposure was studied. The study measured nuclear staining for GATA-3 and FOXA1 in tumor cells, with staining in 1% or more of tumor cells counted as positive.
• Main results:
  • GATA-3 was positive in 115 (96.6%) of 119 ER+ breast carcinomas, 66 (82.2%) of 80 Her2+ breast carcinomas, and 11 (21.6%) of 51 triple-negative breast carcinomas.
  • Among non-breast tumors, GATA-3 was positive only in urothelial carcinomas: 56 (70.9%) of 79. It was negative in all other tumors, including 0 of 15 mesotheliomas.
  • FOXA1 was positive in 127 (96.2%) of 132 ER+ breast carcinomas, 78 (81.3%) of 96 Her2+ breast carcinomas, and 7 (15.9%) of 44 triple-negative breast carcinomas.
  • Among non-breast tumors, FOXA1 was positive in 42 (87.5%) of 48 prostatic adenocarcinomas, 4 (5.1%) of 75 urothelial carcinomas, and 6 (40.0%) of 15 mesotheliomas, and in none of the others.
  • The FOXA1-positive mesotheliomas were 5 epithelioid and 1 biphasic. No lung carcinomas stained for FOXA1.
  • For all breast carcinomas, overall sensitivity and specificity were 76.8% and 77.4% for GATA-3, and 77.9% and 80.3% for FOXA1.
• The authors' conclusion: The authors concluded that GATA-3 and FOXA1 are excellent breast carcinoma markers but have limited utility in triple-negative breast cancer. They said the use of FOXA1 in diagnosing prostatic carcinoma and mesothelioma warrants further investigation.
• Limitations the authors state:
  • The authors said the low GATA-3 positivity in triple-negative breast cancer, compared with other reports, may partly reflect tumor heterogeneity and the use of tissue microarrays.
  • The mesothelioma sample (15 cases) was considerably smaller than in a prior study that found GATA-3 staining in some epithelioid mesotheliomas.
  • Most urothelial carcinomas in the microarray were high-grade, which may explain the low FOXA1 rate in that group.
  • Case numbers differed slightly between the two stains because some tissue cores were lost.

Topics

Medical terms in this study, explained in our Lexicon: Carcinoma, Neoplasm, HER2, Ovarian Serous Carcinoma, Mesothelioma.

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