Evaluation of RET Gene Rearrangement by Fluorescence In Situ Hybridization in Malignant Mesothelioma

Our plain-English summary of Evaluation of RET Gene Rearrangement by Fluorescence In Situ Hybridization in Malignant Mesothelioma, by S. Salvi, J.L. Ravetti, G. Arena, et al (Journal of Thoracic Oncology, 2018).

The study

• Authors: S. Salvi, J.L. Ravetti, G. Arena, C. Musso, S. Varesano, M.P. Pistillo, P.A. Canessa, P. Ferro, F. Fedeli, S. Roncella
• Journal: Journal of Thoracic Oncology
• Published: 2018;13(1):e12-e14
• Type of article: Letter
• Cited by: 4 articles, as counted by NIH iCite
• Read it: PubMed · Publisher

Summary of the article

In this letter, the authors asked whether malignant mesothelioma (MM) carries rearrangements of the RET gene. RET is a tyrosine kinase receptor targeted by drugs such as vandetanib, sunitinib and sorafenib, mainly in RET-rearranged thyroid carcinoma and non-small cell lung cancer. In a retrospective study approved by the Liguria Region Ethics Committee, they examined formalin-fixed paraffin-embedded tissue from 106 MMs (60 epithelioid, 34 sarcomatoid and 12 biphasic). Of these, 79 came from two commercial tissue microarrays (US Biomax), 16 from Ospedale Policlinico San Martino in Genoa and 11 from ASL 5 in La Spezia, Italy. RET status was assessed by fluorescence in situ hybridization (FISH) with a dual-color break-apart probe. A papillary thyroid carcinoma served as a positive control. Signals were counted in almost 50 nuclei per slide, and a case was considered rearranged if more than 15% of cells showed split signals. Two pathologists read the slides independently. None of the 106 MM samples showed a RET rearrangement. The authors described this as, to their knowledge, the first report on RET gene status in MM. They concluded that anti-RET tyrosine kinase inhibitor therapy does not appear applicable in MM. They noted that RET rearrangement in a very small subset of cases cannot be excluded with absolute certainty, and that further studies using other molecular methods are needed.

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 short research letter reported a retrospective laboratory study. The authors looked for rearrangements of the RET gene, a target of some existing cancer drugs, in tumor tissue from 106 malignant mesotheliomas (60 epithelioid, 34 sarcomatoid and 12 biphasic). The samples came from two commercial tissue microarrays (29 and 50 cases) and from pathology units in Genoa (16 cases) and La Spezia (11 cases), Italy. The tissue was tested with fluorescence in situ hybridization (FISH), a staining method that shows whether the gene has been broken apart. A case counted as positive only if more than 15% of cells showed split signals, and two pathologists assessed each case. None of the 106 samples showed a RET rearrangement. The authors concluded that their FISH analysis strongly suggests anti-RET targeted drugs are not applicable in mesothelioma. They said they cannot exclude with absolute certainty that a very small subset of cases carries the rearrangement. They called for studies using other methods, such as testing for RET mutations. The letter did not report asbestos exposure and did not say whether the tumors were pleural or peritoneal.

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 study of archived tumor tissue using fluorescence in situ hybridization (FISH), published as a letter to the editor
• Who was studied: Formalin-fixed paraffin-embedded tissue from 106 malignant mesotheliomas: 60 epithelioid, 34 sarcomatoid and 12 biphasic. Of these, 29 came from the MS801 tissue microarray and 50 from the MS1001 tissue microarray (US Biomax, Rockville, MD), 16 from the Unit of Pathology, Ospedale Policlinico San Martino (Genoa, Italy), and 11 from the Unit of Histopathology, ASL 5 (La Spezia, Italy). The letter does not give dates or the site of the tumors (pleural or peritoneal).
• Main results:
  • None of the 106 malignant mesothelioma tissue samples showed a RET gene rearrangement on FISH.
  • Scoring rule: a case was counted as positive for rearrangement if more than 15% of cells showed split signals. About 50 nuclei were counted per slide, and two pathologists assessed the reactions independently.
• The authors' conclusion: The authors concluded that their FISH analysis strongly suggests that targeted therapies with anti-RET tyrosine kinase inhibitors are not applicable in malignant mesothelioma.
• Limitations the authors state:
  • The authors stated they cannot exclude with absolute certainty that RET rearrangement is present in a very small subset of mesothelioma cases.
  • The authors stated that further studies using other molecular technologies, for example to analyze RET mutations, are needed to fully exclude anti-RET therapies.

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: Fluorescence In Situ Hybridization (FISH), Mesothelioma, Sunitinib (Sutent), Sorafenib (Nexavar), Carcinoma, Non-Small Cell Lung Cancer, Epithelioid, Sarcomatoid.

Related studies

• MET Gene Status in Malignant Mesothelioma Using Fluorescent In Situ Hybridization — S. Varesano, S. Salvi, et al. (2016)
• Fluorescence in situ hybridization (FISH) provides estimates of minute and interstitial BAP1, CDKN2A, and NF2 gene deletions in peritoneal mesothelioma — S. Brich, F. Bozzi, et al. (2020)
• Common Fluorescence In Situ Hybridization Applications in Cytology — S. Savic, L. Bubendorf (2016)
• Fluorescence in situ hybridization in the definitive diagnosis of malignant mesothelioma in effusion cytology — S. Savic, N. Franco, et al. (2010)
• Hemizygous loss of NF2 detected by fluorescence in situ hybridization is useful for the diagnosis of malignant pleural mesothelioma — Y. Kinoshita, M. Hamasaki, et al. (2020)
• MTAP immunohistochemistry is an accurate and reproducible surrogate for CDKN2A fluorescence in situ hybridization in diagnosis of malignant pleural mesothelioma — D.B. Chapel, J.J. Schulte, et al. (2020)

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