The potential utility of GATA binding protein 3 for diagnosis of malignant pleural mesotheliomas

Our plain-English summary of The potential utility of GATA binding protein 3 for diagnosis of malignant pleural mesotheliomas, by S. Prabhakaran, A. Hocking, C. Kim, et al (Human Pathology, 2020).

The study

• Authors: S. Prabhakaran, A. Hocking, C. Kim, M. Hussey, S. Klebe
• Journal: Human Pathology
• Published: 2020;105:1-8
• Cited by: 24 articles, as counted by NIH iCite
• Read it: PubMed · Publisher

Abstract

Malignant pleural mesothelioma is associated with asbestos exposure and poor outcomes. The usefulness of immunohistochemistry for diagnosis of sarcomatoid mesothelioma, especially the desmoplastic type, is limited, and more effective markers are required. GATA binding protein 3 (GATA3) has been suggested as a diagnostic marker for sarcomatoid mesothelioma. The potential usefulness of GATA3 for prognostication and its clinical and pathological correlations in different subtypes of mesothelioma have not been evaluated. We investigated the immunohistochemical labeling and associations for GATA3, BRCA1-associated protein 1 (BAP1), and Ki67 labeling in three major histological types of pleural malignant mesotheliomas. We examined 149 clinically annotated malignant mesotheliomas and assessed associations of GATA3 expression with clinical variables and prognosis. In addition, we labeled 10 cases of fibrous pleuritis with GATA3, all of which were negative. GATA3 was positive in 75 of 149 (50%) mesotheliomas, with the highest incidence of labeling seen in the sarcomatoid subtype (73%), compared with the biphasic (50%) and epithelioid (40%), mesotheliomas. A total of eight desmoplastic mesotheliomas showed labeling with GATA3. Patients whose tumors had sarcomatoid histology showed poorer survival than those with the other subtypes (p < 0.001), but overall GATA3 labeling did not have a statistically significant association with survival (p = 0.602). There was no association of GATA3 labeling and BAP1 status or Ki67 index. Our study includes the largest cohort of mesotheliomas that has been labeled for GATA3 to date. GATA3 is a useful marker for sarcomatoid mesothelioma, including the desmoplastic subtype. Discordance in GATA3 and BAP1 labeling of epithelioid and sarcomatoid components in the biphasic subtype is not uncommon.

Copyright © 2020 Elsevier Inc. All rights reserved.

In plain English

This laboratory study from Flinders Medical Centre in Adelaide, Australia, tested whether a tissue stain for the protein GATA3 helps diagnose malignant pleural mesothelioma. The authors stained tumor tissue from 149 patients diagnosed between 1991 and 2013 (87 epithelioid, 40 sarcomatoid including 8 desmoplastic, 22 biphasic). They also stained 10 samples of fibrous pleuritis, a benign scarring condition of the pleura. The article does not report the patients' asbestos exposure. GATA3 was positive in 75 of 149 tumors (50%): 73% of sarcomatoid, 50% of biphasic and 40% of epithelioid tumors. All 8 desmoplastic tumors showed high GATA3 expression. The fibrous pleuritis samples did not stain, apart from inflammatory cells. Median survival was 5.5 months with sarcomatoid tumors, compared with 15 months (epithelioid) and 8.5 months (biphasic). GATA3 staining was not significantly linked to survival overall. The authors concluded that GATA3 may be a useful additional diagnostic marker for sarcomatoid, especially desmoplastic, mesothelioma, but is not an independent predictor of survival. They described the stain as highly sensitive but not very specific, and noted limited case numbers, particularly of women.

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: Retrospective laboratory (immunohistochemistry) study of archived tumor tissue from a clinically annotated patient cohort, with survival analysis
• Who was studied: 149 patients with pleural mesothelioma diagnosed at Flinders Medical Centre, Adelaide, South Australia, between 1991 and 2013: 87 epithelioid, 40 sarcomatoid (8 of them desmoplastic) and 22 biphasic. 110 were men and 39 women, with a median age of 74 years. Tissue from 10 benign fibrous pleuritis cases was also examined.
• Exposure: The article reports no asbestos exposure data for these patients. What was studied was laboratory staining of tumor tissue for GATA3 (antibody clone L50-823), BAP1 and Ki67.
• Main results:
  • GATA3 staining was positive in 75 of 149 (50%) mesotheliomas overall.
  • GATA3 positivity was 73% (29 of 40) in sarcomatoid, 50% (11 of 22) in biphasic and 40% (35 of 87) in epithelioid mesotheliomas. The association with the sarcomatoid subtype was statistically significant (p = 0.003).
  • All 8 desmoplastic mesotheliomas showed high GATA3 expression, and 4 of the 8 scored higher than 4 on the 0 to 6 scale.
  • The 10 fibrous pleuritis samples showed no GATA3 labeling, except in inflammatory cell infiltrates.
  • Regardless of staining, patients with sarcomatoid tumors had a median survival of 5.5 months, compared with 15 months for epithelioid and 8.5 months for biphasic tumors (p less than 0.001).
  • GATA3-positive cases showed a trend to better survival that was not statistically significant (median 12 months, p = 0.602). In the multivariate analysis, GATA3 was not associated with prognosis overall (hazard ratio 0.788 for high GATA3, 95% CI 0.501 to 1.241, p = 0.304).
  • In the multivariate analysis, the sarcomatoid subtype (hazard ratio 2.61, 95% CI 1.493 to 4.565, p = 0.01) and the biphasic subtype (hazard ratio 1.788, 95% CI 1.021 to 3.131, p = 0.042) were independent markers of poorer survival compared with the epithelioid subtype.
  • Women whose tumors stained for GATA3 had a median survival of 24 months, compared with 9 months for men with GATA3-stained tumors (p = 0.031).
  • Retained BAP1 was associated with GATA3 positivity (p = 0.045). The authors suggested this may reflect histological subtype, because BAP1 loss was associated with the epithelioid type. GATA3 was not associated with Ki67 (p = 0.417), sex or age.
  • In biphasic tumors, GATA3 staining of the epithelioid and sarcomatoid components differed in 5 of 22 (23%) cases and agreed in 17 of 22 (77%).
• The authors' conclusion: The authors concluded that all subtypes can stain for GATA3. Staining was most common in sarcomatoid tumors, which suggests GATA3 may be a useful additional diagnostic marker for sarcomatoid, especially desmoplastic, mesothelioma, and may help tell it apart from fibrous pleuritis. They also concluded that GATA3 was not an independent marker of survival.
• Limitations the authors state:
  • The authors state that GATA3 staining is highly sensitive but not very specific: other tumors can also stain.
  • The authors suggest the lack of a survival difference by GATA3 status within subtypes could be due to the sample size.
  • Because the cohort included few women, the authors consider the prognostic meaning of the better survival in GATA3-positive women uncertain.
  • Uneven and granular GATA3 staining in some tissues could affect how the stain results are interpreted.

Topics

The National Library of Medicine indexes this study under subjects our site covers: Mesothelioma.

Medical terms in this study, explained in our Lexicon: GATA3, Pleural Mesothelioma, Asbestos Exposure, Immunohistochemistry, Sarcomatoid, Mesothelioma, Desmoplastic Mesothelioma, BAP1.

Related studies

• Evaluation of androgen receptor and GATA binding protein 3 as immunohistochemical markers in the diagnosis of metastatic breast carcinoma to the lung — Y. Hattori, A. Yoshida, et al. (2015)
• GATA3 is a useful immunohistochemical marker for distinguishing sarcomatoid malignant mesothelioma from lung sarcomatoid carcinoma and organizing pleuritis — Z.H. Piao, X.C. Zhou, et al. (2021)
• GATA3: a multispecific but potentially useful marker in surgical pathology: a systematic analysis of 2500 epithelial and nonepithelial tumors — M. Miettinen, P.A. McCue, et al. (2014)
• GATA-3 and FOXA1 expression is useful to differentiate breast carcinoma from other carcinomas — D.G. Davis, M.T. Siddiqui, et al. (2016)
• Utility of BAP1 Immunohistochemistry and p16 (CDKN2A) FISH in the Diagnosis of Malignant Mesothelioma in Effusion Cytology Specimens — H.C. Hwang, B.S. Sheffield, et al. (2016)
• GATA3 Immunohistochemistry for Distinguishing Sarcomatoid and Desmoplastic Mesothelioma From Sarcomatoid Carcinoma of the Lung — K.B. Berg, A. Churg (2017)

Browse more research in Human Pathology, or return to medical research.