GATA3 Immunohistochemistry for Distinguishing Sarcomatoid and Desmoplastic Mesothelioma From Sarcomatoid Carcinoma of the Lung

Our plain-English summary of GATA3 Immunohistochemistry for Distinguishing Sarcomatoid and Desmoplastic Mesothelioma From Sarcomatoid Carcinoma of the Lung, by K.B. Berg, A. Churg (The American Journal of Surgical Pathology, 2017).

The study

• Authors: K.B. Berg, A. Churg
• Journal: The American Journal of Surgical Pathology
• Published: 2017;41(9):1221-1225
• Cited by: 54 articles, as counted by NIH iCite
• Read it: PubMed · Publisher

Abstract

The separation of sarcomatoid and desmoplastic malignant mesotheliomas from sarcomatoid carcinomas of the lung metastatic to the pleura may be difficult, since both types of tumor can be morphologically similar and are frequently positive only for pan-keratin. GATA binding protein 3 (GATA3) is most commonly used as an immunohistochemical marker of breast and urothelial carcinoma, but is also known to stain other types of tumors including some mesotheliomas. In this study we asked whether GATA3 stains could be used to distinguish sarcomatoid/desmoplastic malignant mesotheliomas (N=19) from sarcomatoid carcinomas of the lung (N=13). Tumor staining was scored for diffuseness and intensity, with a maximum possible score of 6. All 19 sarcomatoid/desmoplastic malignant mesotheliomas examined showed strong diffuse staining for GATA3 (no case scored <3, mean score±SD for all 19 cases 5.4±0.9), whereas only 2 of 13 sarcomatoid carcinomas of the lung stained positively for GATA3 and the staining was weak and patchy (score 2 for each case, mean±SD for all 13 cases 0.4±0.8). There was no correlation between the intensity and diffuseness of GATA-3 staining and staining for traditional mesothelioma markers. Overall, any positive staining for GATA3 was 100% sensitive and 85% specific for sarcomatoid/desmoplastic mesothelioma. We conclude that strong diffuse staining for GATA3 favors a diagnosis of sarcomatoid/desmoplastic malignant mesothelioma over metastatic sarcomatoid carcinoma of the lung; conversely, complete absence of GATA-3 staining is evidence against a diagnosis of sarcomatoid/desmoplastic malignant mesothelioma.

In plain English

This Canadian laboratory study asked whether a stain called GATA3 helps tell apart two cancers that look alike under the microscope. These are sarcomatoid and desmoplastic malignant mesothelioma, and sarcomatoid (spindle cell) lung carcinoma, which can spread to the pleura. The authors used already-diagnosed cases from one author's consultation files or 2007 to 2016 hospital files: 19 mesotheliomas, all pleural biopsies, and 13 lung sarcomatoid carcinomas. They added 9 sarcomatoid carcinomas from other sites for comparison. Staining was scored from 0 to 6, and 2 or higher counted as positive. All 19 mesotheliomas stained moderately or strongly (mean score 5.4). Of the 13 lung carcinomas, only 3 showed any staining, all weak: 2 scored 2 each and met the positive threshold, and one scored 1, below it. The mean across all 13 was 0.4. The authors reported 100% sensitivity and 85% specificity. Five of the 9 other-site carcinomas also stained. The authors concluded that GATA3 is a sensitive and reasonably specific marker for this distinction, but not when other sarcomatoid carcinomas are possible. The study did not examine asbestos exposure.

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 diagnostic laboratory study (immunohistochemistry) of previously diagnosed tumor specimens
• Who was studied: 19 sarcomatoid/desmoplastic malignant mesothelioma cases (all pleural biopsies) and 13 sarcomatoid carcinomas of the lung (10 primary lung tumors, 3 pleural metastases). For comparison, 9 sarcomatoid carcinomas from other sites were added. Cases came from one author's consultation material or from in-house cases accessioned 2007 to 2016 at Vancouver General Hospital, Canada.
• Exposure: Not reported. The article does not discuss asbestos or any other exposure; it evaluated a laboratory stain (GATA3) as a diagnostic test.
• Main results:
  • All 19 sarcomatoid/desmoplastic mesotheliomas showed GATA3 staining of moderate or strong intensity. All scored 3 or higher, with a mean score of 5.4 (SD 0.9) out of 6.
  • Of the 13 lung sarcomatoid carcinomas, most showed no tumor staining, and only 3 showed any. Two (15%) met the positive threshold, each with a total score of 2, from weak staining of 1% to 25% of tumor nuclei. A third case had weak staining in fewer than 1% of nuclei and scored 1, below the threshold. The mean score across all 13 lung carcinomas was 0.4 (SD 0.8).
  • The third lung carcinoma with staining scored 1, from weak staining in fewer than 1% of nuclei.
  • Mesothelioma and lung carcinoma scores differed significantly (P less than 0.001).
  • Using their scoring system, the authors found GATA3 had 100% sensitivity and 85% specificity for distinguishing sarcomatoid mesothelioma from sarcomatoid carcinoma of the lung.
  • In the mesotheliomas, GATA3 staining did not correlate with the number of traditional mesothelioma markers that were positive (r = 0.14 for intensity, r = 0.11 for diffuseness).
  • Of the 9 sarcomatoid carcinomas from sites other than the lung, 5 were GATA3 positive: urothelial (score 6), laryngeal (6), abdominal of unknown primary (6), renal cell (4) and gallbladder (3).
• The authors' conclusion: The authors concluded that GATA3 is a sensitive and reasonably specific marker for distinguishing sarcomatoid/desmoplastic malignant mesothelioma from sarcomatoid carcinoma of the lung. They added that a sarcomatoid tumor with no GATA3 staining at all is very unlikely to be a mesothelioma.
• Limitations the authors state:
  • The authors stated that GATA3 is useful only when the question is mesothelioma versus lung sarcomatoid carcinoma, not when sarcomatoid carcinomas from other sites are being considered.
  • The results are not absolute: weak, patchy staining can occur in sarcomatoid carcinomas, so judgment is required.
  • A negative result can be trusted only if inflammatory cell nuclei in the sample stain, which confirms the tissue can still take the stain.

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, Immunohistochemistry, Sarcomatoid, Desmoplastic Mesothelioma, Carcinoma, Malignant Mesothelioma, Pleura, Mesothelioma.

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• The potential utility of GATA binding protein 3 for diagnosis of malignant pleural mesotheliomas — S. Prabhakaran, A. Hocking, et al. (2020)
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