Immunohistochemistry for NF2, LATS1/2, and YAP/TAZ Fails to Separate Benign From Malignant Mesothelial Proliferations

Our plain-English summary of Immunohistochemistry for NF2, LATS1/2, and YAP/TAZ Fails to Separate Benign From Malignant Mesothelial Proliferations, by B.S. Sheffield, J. Lorette, Y. Shen, et al (Archives of Pathology & Laboratory Medicine, 2016).

The study

• Authors: B.S. Sheffield, J. Lorette, Y. Shen, M.A. Marra, A. Churg
• Journal: Archives of Pathology & Laboratory Medicine
• Published: 2016;140(5):391
• Type of article: Letter
• Cited by: 18 articles, as counted by NIH iCite
• Read it: PubMed · Publisher

Summary of the article

This letter to the editor reported whether immunohistochemistry for NF2 (merlin), LATS2, and their downstream effector YAP/TAZ could help distinguish mesothelioma from benign mesothelial proliferations. The authors, from Vancouver, British Columbia, Canada, noted that NF2 and LATS1/2 alterations are frequent in mesotheliomas but that their diagnostic usefulness had not been widely explored. The study dates were not stated. The authors validated immunohistochemical assays in-house and applied all 3 markers to a previously characterized tissue microarray containing mesotheliomas and benign mesothelial proliferations. They also stained 2 published mesothelioma cases with comprehensive sequencing for NF2. NF2 loss was found in 1 of 25 mesotheliomas (4%) and 0 of 43 benign proliferations, giving 4% sensitivity and 100% specificity. LATS2 loss occurred in 6 of 22 mesotheliomas (27%) and 9 of 45 benign proliferations (20%), giving 27% sensitivity and 80% specificity. Nuclear YAP/TAZ staining was seen in 22 of 24 mesotheliomas (92%) and 37 of 46 benign proliferations (80%), giving 92% sensitivity and 20% specificity. Both sequenced tumors, one with a frameshift and one with a nonsense NF2 mutation, still stained positive for NF2. The authors concluded that, at least with the antibodies used, these stains were not helpful for separating mesothelioma from benign proliferations.

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 letter to the editor reported a laboratory test of whether three tissue stains could help pathologists tell mesothelioma from benign (non-cancerous) mesothelial proliferations. The authors work in Vancouver, Canada. They applied stains for NF2 (merlin), LATS2 and YAP/TAZ to a previously characterized tissue microarray containing both mesotheliomas and benign mesothelial proliferations. Loss of NF2 staining was found in 1 of 25 mesotheliomas (4%) and 0 of 43 benign proliferations. Loss of LATS2 was found in 6 of 22 mesotheliomas (27%) and 9 of 45 benign proliferations (20%). Nuclear YAP/TAZ staining was found in 22 of 24 mesotheliomas (92%) and 37 of 46 benign proliferations (80%). Two previously published mesothelioma cases had NF2 mutations and were not predicted to make any normal NF2, yet both still stained positive for NF2. The authors concluded that, at least with the antibodies they used, these stains are not helpful for separating mesothelioma from a benign proliferation. The letter did not study asbestos or say whether the microarray mesotheliomas were pleural or peritoneal. The two sequenced cases came from a cited report on malignant peritoneal mesothelioma.

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 laboratory immunohistochemistry validation study on a tissue microarray, plus staining of 2 previously published sequenced cases
• Who was studied: Tissue samples of mesotheliomas and benign mesothelial proliferations on a previously characterized tissue microarray. The anatomical site (pleural or peritoneal) of the microarray cases is not stated. Numbers varied by stain: 25 mesotheliomas and 43 benign for NF2, 22 and 45 for LATS2, and 24 and 46 for YAP/TAZ. Two additional published mesothelioma cases with comprehensive sequencing were also stained for NF2. These were cited from a publication on malignant peritoneal mesothelioma. The authors are based in Vancouver, Canada. Dates and sources of the microarray cases were not stated.
• Exposure: No asbestos or other exposure was studied. The study tested immunohistochemical stains for NF2, LATS2 and YAP/TAZ.
• Main results:
  • NF2 loss: 1 of 25 mesotheliomas (4%) and 0 of 43 benign proliferations (0%). Sensitivity 4%, specificity 100%.
  • LATS2 loss: 6 of 22 mesotheliomas (27%) and 9 of 45 benign proliferations (20%). Sensitivity 27%, specificity 80%.
  • YAP/TAZ nuclear staining: 22 of 24 mesotheliomas (92%) and 37 of 46 benign proliferations (80%). Sensitivity 92%, specificity 20%.
  • Both previously published sequenced mesothelioma cases (NF2 mutations Y177FS and R466*) stained positive for NF2. Both had loss-of-heterozygosity events and were not predicted to express any wild-type NF2.
• The authors' conclusion: The authors concluded that, at least with the antibodies they used, NF2, LATS and YAP/TAZ immunohistochemical stains are not helpful for diagnosing mesothelioma versus a benign proliferation.
• Limitations the authors state:
  • The authors limited their conclusion to the specific antibodies they used.

Topics

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

Medical terms in this study, explained in our Lexicon: Immunohistochemistry, Merlin, Mesothelioma.

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• How asbestos drives the tissue towards tumors: YAP activation, macrophage and mesothelial precursor recruitment, RNA editing, and somatic mutations — H. Rehrauer, L. Wu, et al. (2018)
• LIM-domain protein AJUBA suppresses malignant mesothelioma cell proliferation via Hippo signaling cascade — I. Tanaka, H. Osada, et al. (2015)
• The Emerging Role of the Hippo Pathway in Lung Cancers: Clinical Implications — S.L. Teoh, S. Das (2017)

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