GATA3 is a useful immunohistochemical marker for distinguishing sarcomatoid malignant mesothelioma from lung sarcomatoid carcinoma and organizing pleuritis

Our plain-English summary of GATA3 is a useful immunohistochemical marker for distinguishing sarcomatoid malignant mesothelioma from lung sarcomatoid carcinoma and organizing pleuritis, by Z.H. Piao, X.C. Zhou, J.Y. Chen (Virchows Archiv, 2021).

The study

• Authors: Z.H. Piao, X.C. Zhou, J.Y. Chen
• Journal: Virchows Archiv
• Published: 2021;479(2):257-263
• Cited by: 12 articles, as counted by NIH iCite
• Read it: PubMed · Publisher

Abstract

Sarcomatoid malignant mesothelioma (SMM) tends to occur in the pleura and is morphologically similar to lung sarcomatoid carcinoma (LSC) and organizing pleuritis (OP). Because SMM often does not express mesothelial markers, it is very difficult to distinguish from LSC and OP. GATA-binding protein 3 (GATA3) is a specific immunohistochemical (IHC) marker of breast and urothelial carcinoma. We routinely find that GATA is expressed in MM; however, GATA3 expression in SMM and its reference value for distinguishing SMM from LSC and OP remain unclear. Here, we used IHC methods to detect the expression of GATA3 and classic mesothelial markers in 17 SMM, 12 LSC, and 7 OP cases. We detected the following expression rates in SMM versus LSC cases: GATA3 (70.6% vs. 16.7%, p = 0.008), calretinin (52.9% vs. 8.3%, p = 0.019), Wilms tumor (WT)-1 (64.7% vs. 0%, p = 0.000), D2-40 (47.1% vs. 16.7%, p = 0.126), CK5/6 (35.3% vs. 25.0%, p = 0.694), and pan-cytokeratin (CKpan) (88.2% vs. 100.0%, p = 0.498). The specificities of calretinin, WT-1, and GATA3 in distinguishing SMM from LSC were 91.7%, 100%, and 83.3%, respectively, and combinations of any two of these three markers exhibited 100% specificity for SMM. Notably, the sensitivity of calretinin+/WT1+ staining for SMM was only 23.5%, which increased to 64.7% after including GATA3. Furthermore, all OP cases showed partial or diffuse expression of CKpan, WT-1, and D2-40 but no GATA3 and calretinin expression. In conclusion, GATA3 is an IHC marker with excellent sensitivity and specificity for SMM, and the combined consideration of GATA3, calretinin, and WT-1 was best for distinguishing SMM from LSC. Moreover, CKpan, WT-1, and D2-40 had no value for distinguishing SMM from OP, and GATA3 and calretinin were the most specific markers for distinguishing these two lesions.

© 2021. The Author(s), under exclusive licence to Springer-Verlag GmbH, DE part of Springer Nature.

In plain English

The authors, at the Ningbo Diagnostic Pathology Center in China, tested whether tissue stains (immunohistochemical markers) help tell sarcomatoid malignant mesothelioma (SMM) apart from two look-alike conditions: lung sarcomatoid carcinoma (LSC) and organizing pleuritis (OP), a non-cancerous pleural condition. They stained samples from 17 mesothelioma cases diagnosed between 2012 and 2020 (16 pleural, 1 peritoneal; 15 sarcomatoid, 2 biphasic), 12 LSC cases and 7 OP cases. The article does not discuss asbestos exposure. GATA3 was positive in 12 of 17 mesotheliomas (70.6%) and 2 of 12 LSCs (16.7%). For separating SMM from LSC, the specificities of calretinin, WT-1 and GATA3 were 91.7%, 100% and 83.3%. When any two of these markers were positive together, specificity was 100%. Adding GATA3 to the calretinin-plus-WT-1 combination raised sensitivity from 23.5% to 64.7%. All 7 OP cases were negative for GATA3 and calretinin but showed WT-1, D2-40 and pan-cytokeratin staining. The authors concluded that combining GATA3, calretinin and WT-1 worked best against LSC, and that GATA3 and calretinin were the most specific markers against OP. They noted that the OP group 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 diagnostic study: immunohistochemical staining of selected tissue samples from mesothelioma cases, compared with control groups of lung sarcomatoid carcinoma and organizing pleuritis
• Who was studied: 17 malignant mesothelioma cases diagnosed at the Ningbo Diagnostic Pathology Center, China, between 2012 and 2020: 13 females and 4 males, median age 62 years (range 13 to 78). The cases were 15 sarcomatoid (12 spindle cell type, 3 desmoplastic) and 2 biphasic with a sarcomatoid area of at least 80%. Sixteen arose in the pleura and one in the peritoneum. Controls were 12 lung sarcomatoid carcinoma cases and 7 organizing pleuritis cases.
• Exposure: Not an exposure study; the article reports no asbestos or other fiber exposure. The study tested immunohistochemical markers: GATA3, calretinin, WT-1, D2-40, CK5/6 and pan-cytokeratin (CKpan).
• Main results:
  • GATA3 was positive in 12 of 17 SMM cases (70.6%), 7 of them (41.2%) with diffuse staining. It was positive in 2 of 12 LSC cases (16.7%), with partial staining. The p value for the SMM versus LSC comparison was 0.008.
  • Calretinin was positive in 9 of 17 SMM cases (52.9%) and in 1 of 12 LSC cases (8.3%); p = 0.019.
  • WT-1 (nuclear staining) was positive in 11 of 17 SMM cases (64.7%) and in none of the 12 LSC cases. Eleven of the 12 LSC cases showed cytoplasmic staining only.
  • SMM and LSC did not differ significantly for three markers: D2-40 (47.1% vs. 16.7%, p = 0.126), CK5/6 (35.3% vs. 25.0%, p = 0.694) and CKpan (88.2% vs. 100.0%, p = 0.498).
  • Sensitivities for SMM were 52.9% for calretinin, 64.7% for WT-1 and 70.6% for GATA3. Specificities for distinguishing SMM from LSC were 91.7%, 100% and 83.3%, respectively.
  • When any two of calretinin, WT-1 and GATA3 were positive together, specificity for SMM was 100%.
  • Combined calretinin and WT-1 positivity had a sensitivity for SMM of 23.5%. This rose to 64.7% when GATA3 was included.
  • All 7 OP cases were counted as negative for GATA3 and calretinin, although 2 cases each showed weak staining in a very small number of cells. SMM and OP differed significantly for GATA3 (p = 0.005) and calretinin (p = 0.022).
  • All 7 OP cases showed partial or diffuse staining for WT-1, D2-40 and CKpan. None stained for CK5/6.
  • All 3 desmoplastic mesothelioma cases showed nuclear GATA3 staining in most tumor cells, while all OP cases were negative.
• The authors' conclusion: The authors concluded that GATA3 is an excellent immunohistochemical marker for SMM and that combining GATA3 with calretinin and WT-1 was the best way to distinguish SMM from LSC. They also concluded that CKpan, WT-1 and D2-40 had no value for distinguishing SMM from OP, while GATA3 and calretinin were the most specific markers for that purpose.
• Limitations the authors state:
  • The number of organizing pleuritis cases was small, and more cases are needed.
  • GATA3 staining in other sarcomas or sarcomatoid carcinomas is unknown because few studies exist.
  • In GATA3-positive cases, metastatic sarcomatoid carcinoma, especially from the bladder and breast, needs to be excluded.

Topics

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

Medical terms in this study, explained in our Lexicon: GATA3, Sarcomatoid, Malignant Mesothelioma, Carcinoma, Pleura, Calretinin, Podoplanin (D2-40), Wilms Tumor 1 (WT-1).

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• 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)
• 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)
• How useful is GLUT-1 in differentiating mesothelial hyperplasia and fibrosing pleuritis from epithelioid and sarcomatoid mesotheliomas? An international collaborative study — A.N. Husain, M.K. Mirza, et al. (2014)
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