MET amplification in diffuse pleural mesothelioma and response to savolitinib: a case report

Our plain-English summary of MET amplification in diffuse pleural mesothelioma and response to savolitinib: a case report, by Y. Chen, M. Shen, J. Lv, et al (Translational Lung Cancer Research, 2026).

The study

• Authors: Y. Chen, M. Shen, J. Lv, Y. Rui, C. Xu, D. Wang, T. Lv
• Journal: Translational Lung Cancer Research
• Published: 2026;15(3):66
• Type of article: Case report
• Read it: PubMed · Publisher · Free full text

Abstract

Background: Pleural mesothelioma (PM) is a rare malignancy globally, most frequently associated with alterations in tumor suppressor genes such as NF2, BAP1 and CDKN2A. In contrast, mutations or amplifications of the MET gene are seldomly reported in PM.

Case Description: Here, we report the case of a 60-year-old East Asian male without asbestos exposure, never-smoker, diagnosed with advanced PM. The disease proved refractory to multiple lines of therapy, including platinum-based chemotherapy, immunotherapy, intrathoracic instillation and a subsequent individualized regimen comprising intraperitoneal cisplatin plus sintilimab for local disease control and potential immunomodulation synergized with oral anlotinib. Following disease progression accompanied by rapidly accumulating seroperitoneum and pelvic effusion, next-generation sequencing (NGS) of ascitic fluid revealed MET gene amplification, and the subsequent switch to savolitinib controlled the malignant ascites. Unfortunately, the patient died of sudden cardiac and respiratory arrest in December 2023.

Conclusions: This case underscores the critical importance of comprehensive genetic testing in guiding the treatment of advanced PM, particularly after the failure of standard therapies. It illustrates that rare but actionable genomic alterations, such as MET amplification, can be identified through liquid or tissue biopsy and can inform successful targeted treatment strategies, even in a tumor type where such alterations are uncommon. Histological classification combined with molecular profiling remains pivotal for personalized oncology.

© AME Publishing Company.

In plain English

This was a case report from Jinling Hospital in Nanjing, China, describing a 60-year-old East Asian man, a non-smoker who denied any history of asbestos exposure, with advanced pleural mesothelioma. Genetic testing of fluid around the lung found MAP2K1 and TP53 mutations, and tissue staining was judged highly suggestive of pleural mesothelioma. Chemotherapy plus the immunotherapy drug tislelizumab, and drugs injected into the chest, did not control the fluid build-up, and the cancer spread to the abdomen. A further regimen of cisplatin and sintilimab given into the abdomen, with oral anlotinib, also failed. Testing of the abdominal fluid then found MET gene amplification (copy number 7.54). After a switch to savolitinib, a MET-targeting drug, the chest and abdominal fluid was reported as controlled and symptoms eased. The patient died in December 2023 of what the family reported as a sudden cardiac and respiratory arrest. No autopsy was done. The authors concluded that comprehensive genetic testing can help guide treatment of advanced pleural mesothelioma. They noted that the response was not confirmed by standard imaging criteria.

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: Case report (single patient)
• Who was studied: One 60-year-old East Asian non-smoking man with advanced pleural mesothelioma, referred to Jinling Hospital, Nanjing, China, on July 5, 2023, and followed until his death in December 2023
• Exposure: No asbestos exposure: the patient denied a history of asbestos exposure and was a never-smoker. The exposure studied was treatment, ending with the MET inhibitor savolitinib (400 mg once daily by mouth).
• Main results:
  • Next-generation sequencing of the patient's pleural effusion found MAP2K1 (9% variant allele frequency) and TP53 (11.6% variant allele frequency) mutations
  • In the pleural biopsy, tumor cells stained positive for calretinin, CK, BAP1 and Ki-67 and negative for TTF-1, CEA, NapsinA, WT-1 and p40, findings the authors called highly suggestive of pleural mesothelioma
  • Platinum-based chemotherapy with immunotherapy and intrathoracic injections failed to control fluid in the chest, and fluid developed in the abdomen and pelvis. Abdominal fluid contained malignant cells consistent with metastatic mesothelioma.
  • The individualized regimen of intraperitoneal cisplatin plus sintilimab with oral anlotinib did not control the ascites or systemic progression
  • Sequencing of cell-free DNA from the abdominal fluid found MET amplification (copy number 7.54, Tier I), plus MAP2K1 (15.89% VAF), TP53 (13.09% VAF) and ARID1A (20.02% VAF) mutations. PD-L1 staining was negative.
  • After the switch to savolitinib 400 mg once daily, the chest and abdominal fluid was reported as controlled and abdominal distension and chest tightness were relieved. The patient was discharged on October 16, 2023.
  • The patient died in December 2023. The family reported a sudden cardiac and respiratory arrest at a local hospital, and no autopsy was performed.
• The authors' conclusion: The authors concluded that the case shows the importance of comprehensive genetic testing in guiding treatment of advanced pleural mesothelioma, especially after standard therapies fail. They also concluded that rare alterations such as MET amplification can be found by liquid or tissue biopsy and can inform targeted treatment.
• Limitations the authors state:
  • Response to savolitinib was not confirmed by RECIST-based imaging
  • The short clinical course (death within two months) and the drainage of chest and abdominal fluid given at the same time prevent attributing the benefit solely to savolitinib
  • Archival PET-CT images could not be retrieved for publication, which limits objective assessment of disease burden and response
  • Limited biopsy material prevented additional immunohistochemical and special stains
  • Effusion-based testing was used because tissue was unavailable. Both NGS and FISH results are affected by tumor purity and DNA content.

Topics

Medical terms in this study, explained in our Lexicon: Pleural Mesothelioma, Tumor Suppressor Gene, BAP1, CDKN2A, Asbestos Exposure, Chemotherapy, Immunotherapy, Intrathoracic.

Related studies

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• Asbestosis, pleural plaques and diffuse pleural thickening: three distinct benign responses to asbestos exposure — P.A. Gevenois, V. de Maertelaer, et al. (1998)
• Diffuse pulmonary malignant mesothelioma: response to doxorubicin and 5-azacytidine — A.P. Chahinian, Y. Suzuki, et al. (1978)
• Sarcomatoid diffuse pleural mesothelioma in an 80-year-Old woman with long-term response to nivolumab plus ipilimumab: A case report — Y. Yoshida, H. Mizugaki, et al. (2025)
• Simian virus 40 large T antigen (SV40LTAg) primer specific DNA amplification in human pleural mesothelioma tissue — C. Pepper, B. Jasani, et al. (1996)
• Correlation of MET-Receptor Overexpression with MET Gene Amplification and Patient Outcome in Malignant Mesothelioma — E. Santoni-Rugiu, M.J.S. Lü, et al. (2021)

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