Background: Estimates of the frequency of genomic/proteomic alterations in MET in solid tumors vary widely, but a growing body of evidence suggests that MET amplification and/or Met expression are biomarkers for poor prognosis. We examined both MET gene copy number and Met protein expression as potential prognostic biomarkers for survival in a large set of GEC samples with full clinical annotations (staging, HER2 status, treatment, and overall survival). Methods: Formalin-fixed, paraffin-embedded (FFPE) GEC samples (N = 394) primarily from early-stage tumors were collected in the United States and Italy. Samples were analyzed by fluorescence in situ hybridization (FISH) for MET gene amplification (Dako MET IQFISH probe mix, research use only) and by immunohistochemistry (IHC) for Met protein expression (Dako Met IHC assay, MET4 antibody, investigational use only). All assays were performed according to the manufacturer’s instructions. Samples with a MET/CEP 7 ratio ≥ 2.0 were considered amplified, whereas samples with ≥ 25% Met tumor membrane staining by IHC ( ≥ 1+ intensity) were considered Met positive. Spearman’s rank correlation coefficient was used to assess correlations between parameters. Cox proportional hazards models and Kaplan-Meier estimates were applied to explore relationships between MET, overall survival, and other clinical characteristics. Results: MET gene copy number variation ( ≥ 5 copies) was observed in 18 of 344 samples (5.2%), and MET gene amplification (MET/CEP 7≥ 2.0) was observed in 16 of 344 samples (4.7%). Of the 332 evaluable IHC samples, 117 (35.2%) were positive for Met protein expression. There was considerable overlap between MET amplification and Met expression; 12 of 15 MET-amplified samples (80.0%) were positive for Met expression.Survival analyses showed that both MET gene amplification and Met IHC positivity were prognostic of poor outcomes. Conclusions: MET amplification was observed in ~5% of this large set of GEC samples. Prevalence of MET amplification and Met expression were similar to those found in previously published studies. Our results indicate that MET gene amplification and Met protein expression are prognostic of poor outcomes in GEC.
MET as a prognostic biomarker of survival in a large cohort of patients with gastroesophageal cancer (GEC)
RUZZO, ANNAMARIA;
2015
Abstract
Background: Estimates of the frequency of genomic/proteomic alterations in MET in solid tumors vary widely, but a growing body of evidence suggests that MET amplification and/or Met expression are biomarkers for poor prognosis. We examined both MET gene copy number and Met protein expression as potential prognostic biomarkers for survival in a large set of GEC samples with full clinical annotations (staging, HER2 status, treatment, and overall survival). Methods: Formalin-fixed, paraffin-embedded (FFPE) GEC samples (N = 394) primarily from early-stage tumors were collected in the United States and Italy. Samples were analyzed by fluorescence in situ hybridization (FISH) for MET gene amplification (Dako MET IQFISH probe mix, research use only) and by immunohistochemistry (IHC) for Met protein expression (Dako Met IHC assay, MET4 antibody, investigational use only). All assays were performed according to the manufacturer’s instructions. Samples with a MET/CEP 7 ratio ≥ 2.0 were considered amplified, whereas samples with ≥ 25% Met tumor membrane staining by IHC ( ≥ 1+ intensity) were considered Met positive. Spearman’s rank correlation coefficient was used to assess correlations between parameters. Cox proportional hazards models and Kaplan-Meier estimates were applied to explore relationships between MET, overall survival, and other clinical characteristics. Results: MET gene copy number variation ( ≥ 5 copies) was observed in 18 of 344 samples (5.2%), and MET gene amplification (MET/CEP 7≥ 2.0) was observed in 16 of 344 samples (4.7%). Of the 332 evaluable IHC samples, 117 (35.2%) were positive for Met protein expression. There was considerable overlap between MET amplification and Met expression; 12 of 15 MET-amplified samples (80.0%) were positive for Met expression.Survival analyses showed that both MET gene amplification and Met IHC positivity were prognostic of poor outcomes. Conclusions: MET amplification was observed in ~5% of this large set of GEC samples. Prevalence of MET amplification and Met expression were similar to those found in previously published studies. Our results indicate that MET gene amplification and Met protein expression are prognostic of poor outcomes in GEC.I documenti in IRIS sono protetti da copyright e tutti i diritti sono riservati, salvo diversa indicazione.
