SMARCA4 Loss Is Very Rare in Thoracic Mesothelioma

Our plain-English summary of SMARCA4 Loss Is Very Rare in Thoracic Mesothelioma, by M.S. Ahadi, A.J. Gill (The American Journal of Surgical Pathology, 2019).

The study

• Authors: M.S. Ahadi, A.J. Gill
• Journal: The American Journal of Surgical Pathology
• Published: 2019;43(8):1154-1155
• Type of article: Letter, Comment
• Cited by: 11 articles, as counted by NIH iCite
• Read it: PubMed · Publisher

Summary of the article

This letter to the editor responded to a study by Perret et al that reported loss of SMARCA4 in 4 of 31 (13%) epithelioid mesotheliomas. The authors had not previously seen SMARCA4 loss in mesothelioma, so they examined how often it occurred in their own single-institution series. They performed immunohistochemistry for SMARCA4 and SMARCA2 on a tissue microarray containing two 1 mm cores from all available mesotheliomas encountered at their institution from 1992 to 2016. They repeated negative, weak or equivocal stains on whole slides. Of 296 assessable mesotheliomas, 179 (60.5%) were epithelioid, 63 (21.3%) sarcomatoid and 54 (18.2%) biphasic. Complete loss of SMARCA4 was found in only 2 tumours, both epithelioid. This was 0.7% of all cases and 1.1% of epithelioid cases. No case showed loss of SMARCA2. The two patients, a 77-year-old woman and a 76-year-old man, had pleurally based lesions and a history of asbestos exposure. They died 9 and 4 months after diagnosis. Both tumours showed only focal weak staining for the mesothelial markers WT1 and calretinin, and one showed focal weak TTF1 and BerEP4. The authors therefore could not fully exclude poorly differentiated carcinoma. They concluded that SMARCA4 loss is very rare in mesothelioma. They suggested that the higher rate reported by Perret et al might reflect small sample size and selection bias. They also suggested that, if confirmed, SMARCA4 status may help distinguish mesothelioma from SMARCA4-deficient thoracic sarcoma and lung adenocarcinoma.

PubMed has no abstract for this study, and the article doesn't print one. We wrote this summary from the full article with the help of AI. It is not the authors' wording.

In plain English

This was a letter to the editor responding to an earlier study by Perret and colleagues, which had reported SMARCA4 protein loss in 4 of 31 epithelioid mesotheliomas. The authors checked how often this loss occurred in all available mesotheliomas seen at their own institution from 1992 to 2016. They stained tumor samples for the SMARCA4 and SMARCA2 proteins. Of 296 mesotheliomas that could be assessed (179 epithelioid, 63 sarcomatoid, 54 biphasic), only 2 showed complete loss of SMARCA4, both epithelioid. That was 0.7% of all cases and 1.1% of epithelioid cases. None of the 296 showed SMARCA2 loss. The two patients, a 77-year-old woman and a 76-year-old man, had pleurally based tumors and a history of asbestos exposure. They died 9 and 4 months after diagnosis. Their staining pattern was not clear-cut, and the authors could not completely exclude that these were poorly differentiated carcinomas rather than mesotheliomas. The authors concluded that SMARCA4 loss occurs very rarely in mesothelioma. They suggested the higher figure in the earlier study might reflect small sample size and selection bias.

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: Letter to the editor reporting a single-institution laboratory (immunohistochemistry) series, with review of the two cases showing protein loss
• Who was studied: All available mesotheliomas seen at the authors' institution from 1992 to 2016; 296 could be assessed (179 epithelioid, 63 sarcomatoid, 54 biphasic)
• Exposure: The study measured SMARCA4 and SMARCA2 protein staining in tumors and did not study asbestos exposure as such. The two SMARCA4-deficient patients were reported to have a clinical history of asbestos exposure.
• Main results:
  • 296 mesotheliomas could be assessed: 179 epithelioid (60.5%), 63 sarcomatoid (21.3%) and 54 biphasic (18.2%)
  • Complete SMARCA4 loss was found in 2 of the 296 mesotheliomas, both epithelioid
  • These 2 cases were 0.7% of the whole cohort and 1.1% of epithelioid mesotheliomas
  • No mesothelioma in the cohort showed loss of SMARCA2
  • Both SMARCA4-deficient patients (a 77-year-old woman and a 76-year-old man) had pleurally based lesions
  • The two SMARCA4-deficient patients died 9 and 4 months after diagnosis, respectively
  • The staining profile of the two cases was not clear-cut. Both showed only focal weak staining for the mesothelial markers WT1 and calretinin, and one case also showed focal weak staining for the epithelial markers TTF1 and BerEP4.
  • The authors suggested that the 13% rate in Perret et al could be due to other factors, including small sample size and selection bias toward difficult consultation cases
• The authors' conclusion: The authors concluded that SMARCA4 loss occurs very rarely in mesothelioma and SMARCA2 loss even more rarely. If confirmed, SMARCA4 status may help distinguish mesothelioma from SMARCA4-deficient thoracic sarcoma and SMARCA4-deficient lung adenocarcinoma.
• Limitations the authors state:
  • The authors could not completely exclude that the two SMARCA4-deficient cases were poorly differentiated carcinomas rather than mesotheliomas

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: Mesothelioma, Epithelioid, Immunohistochemistry, Sarcomatoid, Biphasic Mesothelioma, Asbestos Exposure, Calretinin, Carcinoma.

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