Plasma cell membrane localization of c-MET predicts longer survival in patients with malignant mesothelioma : a series of 157 cases from the MESOPATH Group
INTRODUCTION: By regulating cell functions such as growth, survival, motility/migration, and invasion, the c-mesenchymal-epithelial transition (c-MET) receptor tyrosine kinase/hepatocyte growth factor (HGF) axis accounts for a critical pathway in malignant pleural mesothelioma.
METHODS: Overall survival correlations of c-MET and phospho-c-MET immunostainings were investigated in 157 malignant pleural mesothelioma patients for whom paraffin-embedded specimens were referred to our center for pathological diagnosis certification (MESOPATH French National group). Subcellular localization of the activated c-MET receptor after HGF stimulation was assessed in nontumorogenic cell lines.
RESULTS: Positive c-MET expression was found in 119 samples (75.8%), more frequently in the epithelioid subtype (p < 0.0001). Among those 119 positive c-MET specimens, 77 (64.7%) were also positive for phospho-c-MET. Both c-MET and phospho-c-MET scoring were independent of patient gender or age. Phospho-c-MET scoring or localization did not associate with survival. Conversely, patients with a c-MET immunohistochemical staining intensity higher than 1, but exclusively confined to plasma membrane, had a median overall survival of 25 months versus 13 months for all other patients. Only exclusive plasma membrane staining remained significantly associated with a worse prognosis in multivariate analysis (hazard ratio = 2.9, 95% confidence interval 1.0-8.2, p = 0.043). Using the HBEC3 immortalized epithelial cell lines treated with HGF, we showed the physiological relevance of phospho-c-MET nuclear translocation.
CONCLUSIONS: Our results lighten that, disregarding the intracellular c-MET receptor traffic, only c-MET plasma membrane localization could be a relevant prognosis biomarker in malignant pleural mesothelioma. Whether patients with c-MET plasma membrane immunostaining could beneficiate from c-MET-targeted therapies remains to be established in prospective trials.
| Medienart: |
E-Artikel |
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| Erscheinungsjahr: |
2012 |
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| Erschienen: |
2012 |
| Enthalten in: |
Zur Gesamtaufnahme - volume:7 |
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| Enthalten in: |
Journal of thoracic oncology : official publication of the International Association for the Study of Lung Cancer - 7(2012), 3 vom: 07. März, Seite 599-606 |
| Sprache: |
Englisch |
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| Beteiligte Personen: |
Levallet, Guénaëlle [VerfasserIn] |
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| Links: |
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| Themen: |
EC 2.7.10.1 |
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| Anmerkungen: |
Date Completed 14.06.2012 Date Revised 02.01.2021 published: Print Citation Status MEDLINE |
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| doi: |
10.1097/JTO.0b013e3182417da5 |
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| funding: |
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| Förderinstitution / Projekttitel: |
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| PPN (Katalog-ID): |
NLM214565831 |
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| 100 | 1 | |a Levallet, Guénaëlle |e verfasserin |4 aut | |
| 245 | 1 | 0 | |a Plasma cell membrane localization of c-MET predicts longer survival in patients with malignant mesothelioma |b a series of 157 cases from the MESOPATH Group |
| 264 | 1 | |c 2012 | |
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| 500 | |a Date Revised 02.01.2021 | ||
| 500 | |a published: Print | ||
| 500 | |a Citation Status MEDLINE | ||
| 520 | |a INTRODUCTION: By regulating cell functions such as growth, survival, motility/migration, and invasion, the c-mesenchymal-epithelial transition (c-MET) receptor tyrosine kinase/hepatocyte growth factor (HGF) axis accounts for a critical pathway in malignant pleural mesothelioma | ||
| 520 | |a METHODS: Overall survival correlations of c-MET and phospho-c-MET immunostainings were investigated in 157 malignant pleural mesothelioma patients for whom paraffin-embedded specimens were referred to our center for pathological diagnosis certification (MESOPATH French National group). Subcellular localization of the activated c-MET receptor after HGF stimulation was assessed in nontumorogenic cell lines | ||
| 520 | |a RESULTS: Positive c-MET expression was found in 119 samples (75.8%), more frequently in the epithelioid subtype (p < 0.0001). Among those 119 positive c-MET specimens, 77 (64.7%) were also positive for phospho-c-MET. Both c-MET and phospho-c-MET scoring were independent of patient gender or age. Phospho-c-MET scoring or localization did not associate with survival. Conversely, patients with a c-MET immunohistochemical staining intensity higher than 1, but exclusively confined to plasma membrane, had a median overall survival of 25 months versus 13 months for all other patients. Only exclusive plasma membrane staining remained significantly associated with a worse prognosis in multivariate analysis (hazard ratio = 2.9, 95% confidence interval 1.0-8.2, p = 0.043). Using the HBEC3 immortalized epithelial cell lines treated with HGF, we showed the physiological relevance of phospho-c-MET nuclear translocation | ||
| 520 | |a CONCLUSIONS: Our results lighten that, disregarding the intracellular c-MET receptor traffic, only c-MET plasma membrane localization could be a relevant prognosis biomarker in malignant pleural mesothelioma. Whether patients with c-MET plasma membrane immunostaining could beneficiate from c-MET-targeted therapies remains to be established in prospective trials | ||
| 650 | 4 | |a Journal Article | |
| 650 | 4 | |a Multicenter Study | |
| 650 | 7 | |a MET protein, human |2 NLM | |
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| 700 | 1 | |a Vaisse-Lesteven, Mélissa |e verfasserin |4 aut | |
| 700 | 1 | |a Le Stang, Nolwenn |e verfasserin |4 aut | |
| 700 | 1 | |a Ilg, Anabelle Gilg Soit |e verfasserin |4 aut | |
| 700 | 1 | |a Brochard, Patrick |e verfasserin |4 aut | |
| 700 | 1 | |a Astoul, Philippe |e verfasserin |4 aut | |
| 700 | 1 | |a Pairon, Jean Claude |e verfasserin |4 aut | |
| 700 | 1 | |a Bergot, Emmanuel |e verfasserin |4 aut | |
| 700 | 1 | |a Zalcman, Gérard |e verfasserin |4 aut | |
| 700 | 1 | |a Galateau-Sallé, Francoise |e verfasserin |4 aut | |
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