Xavier Mignard1, Anne-Marie Ruppert2, Martine Antoine3, Julie Vasseur4, Nicolas Girard5, Julien Mazières6, Denis Moro-Sibilot7, Vincent Fallet8, Nathalie Rabbe8, Françoise Thivolet-Bejui9, Isabelle Rouquette10, Sylvie Lantuejoul11, Alexis Cortot12, Raphaël Saffroy4, Jacques Cadranel2, Antoinette Lemoine4, Marie Wislez13. 1. Sorbonne University, GRC n°04, Theranoscan, F-75252, Paris, France. 2. Sorbonne University, GRC n°04, Theranoscan, F-75252, Paris, France; AP-HP, GH HUEP, Tenon Hospital, Chest Department and Thoracic Oncology, F-75970, Paris, France. 3. Sorbonne University, GRC n°04, Theranoscan, F-75252, Paris, France; AP-HP, GH HUEP, Tenon Hospital, Cytology and Pathology Department, F-75970, Paris, France. 4. AP-HP, GH Paris-Sud, Paul Brousse Hospital, Department of Biochiemistry and Oncogenetics, Platform Oncomolpath/INCa, Villejuif, France. 5. Respiratory Medicine and Thoracic Oncology Service, Louis Pradel Hospital, Hospices Civils de Lyon, Lyon, France. 6. Larrey University Hospital, Toulouse, France. 7. Grenoble University Hospital, A. Michalon Hospital, La Tronche, France. 8. AP-HP, GH HUEP, Tenon Hospital, Chest Department and Thoracic Oncology, F-75970, Paris, France. 9. Biology and Pathology East Center, Hospices Civils de Lyon Lyon, France. 10. Toulouse Universitary Cancer Institute, IUCT-Oncopole, Pathology Department, Toulouse, France. 11. Biopathology Department, Léon Bérard Center, Unicancer Grenoble, France; Grenoble Alpes University, Grenoble, France. 12. CHU Lille, Thoracic Oncology Department, Univ. Lille, Siric ONCOLille, Lille, France. 13. Sorbonne University, GRC n°04, Theranoscan, F-75252, Paris, France; AP-HP, GH HUEP, Tenon Hospital, Chest Department and Thoracic Oncology, F-75970, Paris, France. Electronic address: marie.wislez@aphp.fr.
Abstract
INTRODUCTION: MNNG HOS transforming gene (MET) abnormalities such as amplification and exon 14 mutations may be responsive to targeted therapies. They are prevalent in lung sarcomatoid carcinomas (LSCs) and must be diagnosed as efficiently as possible. Hypothetically, c-MET overexpression by immunohistochemistry (IHC) may prove effective as a screening test for MET abnormalities. METHODS: Tissue samples were obtained from consecutive patients with a resected LSC in four oncologic centers. IHC was performed using the SP44 antibody (Ventana, Tucson, Arizona) and evaluated using the MetMab score and H-score. Fluorescence in situ hybridization was applied with the dual color probe set from Zytovision (Clinisciences, Nanterre, France). True MET amplification was diagnosed when MET gene copy number was 5 or greater and the ratio between MET gene copy number and chromosome 7 number was greater than 2. All MET exon 14 alterations including those affecting splice sites occurring within splice donor and acceptor sites were detected in the routine molecular testing on genetic platforms. RESULTS: A total of 81 LSCs were included. Fourteen (17%) exhibited positive IHC using the MetMab score and 15 (18.5%) using the H-score. MET amplification was detected in six tumors (8.5%) and MET exon 14 mutation in five (6%). A weak positive correlation between IHC and fluorescence in situ hybridization was found (r = 0.27, p = 0.0001). IHC sensitivity for MET amplification was 50%, with a specificity of 83%, positive predictive value of 21.4%, and negative predictive value of 94.7%. IHC sensitivity for MET exon 14 mutations was 20%, with a specificity of 83%, positive predictive value of 7%, and negative predictive value of 94%. CONCLUSION: IHC is not a relevant screening tool for MET abnormalities in LSC.
INTRODUCTION: MNNG HOS transforming gene (MET) abnormalities such as amplification and exon 14 mutations may be responsive to targeted therapies. They are prevalent in lung sarcomatoid carcinomas (LSCs) and must be diagnosed as efficiently as possible. Hypothetically, c-MET overexpression by immunohistochemistry (IHC) may prove effective as a screening test for MET abnormalities. METHODS: Tissue samples were obtained from consecutive patients with a resected LSC in four oncologic centers. IHC was performed using the SP44 antibody (Ventana, Tucson, Arizona) and evaluated using the MetMab score and H-score. Fluorescence in situ hybridization was applied with the dual color probe set from Zytovision (Clinisciences, Nanterre, France). True MET amplification was diagnosed when MET gene copy number was 5 or greater and the ratio between MET gene copy number and chromosome 7 number was greater than 2. All MET exon 14 alterations including those affecting splice sites occurring within splice donor and acceptor sites were detected in the routine molecular testing on genetic platforms. RESULTS: A total of 81 LSCs were included. Fourteen (17%) exhibited positive IHC using the MetMab score and 15 (18.5%) using the H-score. MET amplification was detected in six tumors (8.5%) and MET exon 14 mutation in five (6%). A weak positive correlation between IHC and fluorescence in situ hybridization was found (r = 0.27, p = 0.0001). IHC sensitivity for MET amplification was 50%, with a specificity of 83%, positive predictive value of 21.4%, and negative predictive value of 94.7%. IHC sensitivity for MET exon 14 mutations was 20%, with a specificity of 83%, positive predictive value of 7%, and negative predictive value of 94%. CONCLUSION: IHC is not a relevant screening tool for MET abnormalities in LSC.
Authors: Robin Guo; Lynne D Berry; Dara L Aisner; Jamie Sheren; Theresa Boyle; Paul A Bunn; Bruce E Johnson; David J Kwiatkowski; Alexander Drilon; Lynette M Sholl; Mark G Kris Journal: J Thorac Oncol Date: 2019-06-20 Impact factor: 15.609
Authors: Na Wang; Yili Zhu; Ying Wu; Bo Huang; Junhua Wu; Ruiguang Zhang; Jun Fan; Xiu Nie Journal: J Cancer Res Clin Oncol Date: 2022-07-29 Impact factor: 4.322