title: Clinical impact of the HGF/MET pathway activation in patients with advanced gastric cancer treated with palliative chemotherapy.
abstract: In gastric cancer, available clinical studies focusing on the activated hepatocyte growth factor (HGF)/MET pathway are limited to surgical and often heterogeneous series. MET copy number gain (CNG) and an activating truncation in the HGF promoter (deoxyadenosine tract element, DATE+) were studied in tumors of 95 patients with advanced gastric cancer treated with palliative chemotherapy. Associations with overall survival (OS) and the pattern of metastatic disease were studied. Median OS was 9.7 months in 80 MET CNG <5 copies cases (MET-), and 6.4 months in 15 MET CNG was ⩾5 copies cases (MET+) (P=0.001). MET+ status confirmed the adverse prognostic effect in the multivariate model. A significantly different distribution of MET+/DATE+ and MET-/DATE- cases was observed between patients with and without peritoneal carcinomatosis (PC). MET+ status confirms its adverse prognostic role in advanced gastric cancer patients. The activated MET/HGF axis seems to be associated with PC. These findings are relevant to the development of anti-MET/HGF compounds.
authors.affiliation: Department of Onco-Hematology, Division of Medical Oncology, Azienda Ospedaliera 'Ospedali Riuniti Marche Nord', Pesaro, Italy.
authors.forename: F
authors.initials: F
authors.lastname: Graziano
authors.affiliation: Department of Onco-Hematology, Division of Medical Oncology, Azienda Ospedaliera 'Ospedali Riuniti Marche Nord', Pesaro, Italy.
authors.forename: V
authors.initials: V
authors.lastname: Catalano
authors.affiliation: Department of Histopathology, Azienda Ospedaliera 'Ospedali Riuniti Marche Nord', Pesaro, Italy.
authors.forename: P
authors.initials: P
authors.lastname: Lorenzini
authors.affiliation: Department of Biomolecular Sciences, University of Urbino 'Carlo Bo', Urbino, Italy.
authors.forename: E
authors.initials: E
authors.lastname: Giacomini
authors.affiliation: Department of Onco-Hematology, Division of Medical Oncology, Azienda Ospedaliera 'Ospedali Riuniti Marche Nord', Pesaro, Italy.
authors.forename: D
authors.initials: D
authors.lastname: Sarti
authors.affiliation: Department of Onco-Hematology, Division of Medical Oncology, Azienda Ospedaliera 'Ospedali Riuniti Marche Nord', Pesaro, Italy.
authors.forename: G
authors.initials: G
authors.lastname: Fiorentini
authors.affiliation: Department of Histopathology, Azienda Ospedaliera 'Ospedali Riuniti Marche Nord', Pesaro, Italy.
authors.forename: M
authors.initials: M
authors.lastname: De Nictolis
authors.affiliation: Department of Biomolecular Sciences, University of Urbino 'Carlo Bo', Urbino, Italy.
authors.forename: M
authors.initials: M
authors.lastname: Magnani
authors.affiliation: Department of Biomolecular Sciences, University of Urbino 'Carlo Bo', Urbino, Italy.
authors.forename: A
authors.initials: A
authors.lastname: Ruzzo
mesh_terms: D000368:Aged; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D005260:Female; D017228:Hepatocyte Growth Factor / Q000235:genetics / Q000378:metabolism*; D006801:Humans; D008297:Male; D010166:Palliative Care; D019859:Proto-Oncogene Proteins c-met / Q000235:genetics / Q000378:metabolism*; D012189:Retrospective Studies; D013274:Stomach Neoplasms / Q000188:drug therapy* / Q000235:genetics / Q000378:metabolism*; D015996:Survival Rate
chemical_list: D017228:Hepatocyte Growth Factor; D019859:Proto-Oncogene Proteins c-met