Plasma Cell Membrane Localization of c-MET Predicts Longer Survival in Patients with Malignant Mesothelioma: A Series of 157 Cases from the MESOPATH Group

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Plasma Cell Membrane Localization of c-MET Predicts Longer Survival in Patients with Malignant Mesothelioma: A Series of 157 Cases from the MESOPATH Group Guénaëlle Levallet, PhD, Mélissa Vaisse-Lesteven, MSc, Nolwenn Le Stang, MS, Anabelle Gilg Soit Ilg, MD, Patrick Brochard, MD, Philippe Astoul, MD, Jean Claude Pairon, MD, Emmanuel Bergot, MD, Gérard Zalcman, MD, PhD, Francoise Galateau-Sallé, MD, PhD Journal of Thoracic Oncology Volume 7, Issue 3, Pages 599-606 (March 2012) DOI: 10.1097/JTO.0b013e3182417da5 Copyright © 2012 International Association for the Study of Lung Cancer Terms and Conditions

Figure 1 Representative intensity of c-MET or phospho-c-MET immunostaining in malignant pleural mesothelioma (MPM). MPM tumors were stained with anti-c-MET (upper panels) or phospho-c-MET (lower panels) antibody as described in the “Patients and Methods” section. Pictures illustrate representative intensities: weak (I1), moderate (I2), and strong (I3) measured. Internal positive controls were normal epithelial cells. Journal of Thoracic Oncology 2012 7, 599-606DOI: (10.1097/JTO.0b013e3182417da5) Copyright © 2012 International Association for the Study of Lung Cancer Terms and Conditions

Figure 2 Representative subcellular localization of phospho-c-MET immunostaining in malignant pleural mesothelioma (MPM). MPM tumors were stained with antiphospho-c-MET antibody as described in the “Patients and Methods” section. Pictures illustrate representative subcellular localization observed. Internal positive controls were normal epithelial cells. Journal of Thoracic Oncology 2012 7, 599-606DOI: (10.1097/JTO.0b013e3182417da5) Copyright © 2012 International Association for the Study of Lung Cancer Terms and Conditions

Figure 3 c-MET subcellular localization according its immunostaining intensity. Malignant pleural mesothelioma (MPM) tumors were stained with anti-c-MET antibody as described in the “Patients and Methods” section. For each intensity, set of histogram represent percentage of case number counted in each subcellular compartment. Journal of Thoracic Oncology 2012 7, 599-606DOI: (10.1097/JTO.0b013e3182417da5) Copyright © 2012 International Association for the Study of Lung Cancer Terms and Conditions

Figure 4 Nuclear translocation of phospho-c-MET in HBEC3 cells under hepatocyte growth factor (HGF) stimulation. HBEC3 cells were cultivated for 24 hours in KSFM devoid of EGFr and BPE, then stimulated 5, 10, 15, or 20 minutes with HGF (40 ng/ml) or not. A, Confocal laser scanning images of HBEC3 cells stained for c-MET, phospho-c-MET, or alpha-tubulin followed by a Texas-red-conjugated secondary antibody. Scale bar = 50 μm. B, Representative Western blot performed with antiphospho-c-MET antibody (see Patients and Methods section) and its analyses. Ratios of phospho-c-MET expression compared with the normalizer of each fraction were determined in three separate cultures. Values are mean ± SEM. Positive control is extract from H1975 cell line. Journal of Thoracic Oncology 2012 7, 599-606DOI: (10.1097/JTO.0b013e3182417da5) Copyright © 2012 International Association for the Study of Lung Cancer Terms and Conditions

Figure 5 c-MET intensity staining (IS) relationship with overall survival rate. The overall survival rate curve for the 157 patients from the MESOPATH group is presented according to c-MET intensity staining expression. Journal of Thoracic Oncology 2012 7, 599-606DOI: (10.1097/JTO.0b013e3182417da5) Copyright © 2012 International Association for the Study of Lung Cancer Terms and Conditions

Figure 6 c-MET subcellular localization relationship with overall survival rate. The overall survival rate curve for the 157 patients from the MESOPATH group is presented according to c-MET subcellular localization. Journal of Thoracic Oncology 2012 7, 599-606DOI: (10.1097/JTO.0b013e3182417da5) Copyright © 2012 International Association for the Study of Lung Cancer Terms and Conditions