{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,29]],"date-time":"2026-09-29T17:13:29Z","timestamp":1790702009138,"version":"4.1.0"},"reference-count":29,"publisher":"MDPI AG","issue":"23","license":[{"start":{"date-parts":[[2021,11,28]],"date-time":"2021-11-28T00:00:00Z","timestamp":1638057600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Research Council of Rigshospitalet, Copenhagen University Hospital","award":["PSP E-22360-01"],"award-info":[{"award-number":["PSP E-22360-01"]}]},{"name":"Kommune Hospitalets 100 \u00e5rs Jubil\u00e6ums Foundation","award":["No grant number"],"award-info":[{"award-number":["No grant number"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Thanks to clinically newly introduced inhibitors of the mesenchymal\u2013epithelial transition (MET) receptor tyrosine-kinase, MET-gene copy number gain\/amplification (MET-GCNG\/GA) and increased expression of the MET protein are considered very promising therapeutic targets in lung cancer and other malignancies. However, to which extent these MET alterations occur in malignant mesothelioma (MM) remains unclear. Thus, we investigated by well-established immunohistochemistry and fluorescence in situ hybridization methods, the frequency of these alterations in specimens from 155 consecutive MMs of different subtypes obtained from pleural or peritoneal biopsies and pleurectomies. Thirty-three benign reactive mesothelial proliferations (RMPs) were used as controls. MET-protein upregulation was observed in 35% of all MM-cases, though restricted to predominantly epithelioid MMs. We detected low-\/intermediate-level MET-GCNG\/GA in 22.2% of MET-overexpressing MMs (7.8% of whole MM-cohort) and no MET-GCNG\/GA in the other 77.8%, suggesting other upregulating mechanisms. In contrast, 100% of RMPs exhibited no MET-upregulation or MET-GCNG\/-GA. Neither MET exon 14 skipping mutations nor MET-fusions were detected as mechanisms of MET overexpression in MM using RNA next-generation sequencing. Finally, in two cohorts of 30 MM patients with or without MET overexpression (MET-positive\/-negative) that were matched for several variables and received the same standard chemotherapy, the MET-positive cases showed a significantly lower response rate, but no significant difference in progression-free or overall survival. Our results imply that MET overexpression occurs in a substantial fraction of predominantly epithelioid MMs, but correlates poorly with MET-amplification status, and may impact the likelihood of response to mesothelioma standard chemotherapy. The predictive significance of MET-IHC and -FISH for possible MET-targeted therapy of MM remains to be elucidated.<\/jats:p>","DOI":"10.3390\/ijms222312868","type":"journal-article","created":{"date-parts":[[2021,11,30]],"date-time":"2021-11-30T23:22:28Z","timestamp":1638314548000},"page":"12868","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":5,"title":["Correlation of MET-Receptor Overexpression with MET Gene Amplification and Patient Outcome in Malignant Mesothelioma"],"prefix":"10.3390","volume":"22","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-2283-3535","authenticated-orcid":false,"given":"Eric","family":"Santoni-Rugiu","sequence":"first","affiliation":[{"name":"Department of Pathology\/Danish National Mesothelioma Center, Rigshospitalet, Copenhagen University Hospital, DK-2100 Copenhagen, Denmark"},{"name":"Biotech Research & Innovation Centre (BRIC), University of Copenhagen, DK-2200 Copenhagen, Denmark"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4839-4040","authenticated-orcid":false,"given":"Maya Jeje Schuang","family":"L\u00fc","sequence":"additional","affiliation":[{"name":"Department of Oncology\/Danish National Mesothelioma Center, Rigshospitalet, Copenhagen University Hospital, DK-2100 Copenhagen, Denmark"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jan Nyrop","family":"Jakobsen","sequence":"additional","affiliation":[{"name":"Department of Oncology\/Danish National Mesothelioma Center, Rigshospitalet, Copenhagen University Hospital, DK-2100 Copenhagen, Denmark"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Linea Cecilie","family":"Melchior","sequence":"additional","affiliation":[{"name":"Department of Pathology\/Danish National Mesothelioma Center, Rigshospitalet, Copenhagen University Hospital, DK-2100 Copenhagen, Denmark"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jesper","family":"Ravn","sequence":"additional","affiliation":[{"name":"Department of Thoracic Surgery\/Danish National Mesothelioma Center, Copenhagen University Hospital, DK-2100 Copenhagen, Denmark"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7780-0178","authenticated-orcid":false,"given":"Jens Benn","family":"S\u00f8rensen","sequence":"additional","affiliation":[{"name":"Department of Oncology\/Danish National Mesothelioma Center, Rigshospitalet, Copenhagen University Hospital, DK-2100 Copenhagen, Denmark"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2021,11,28]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"341","DOI":"10.1038\/s41568-018-0002-y","article-title":"Known and novel roles of the MET oncogene in cancer: A coherent approach to targeted therapy","volume":"18","author":"Comoglio","year":"2018","journal-title":"Nat. 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