PMID- 27926778
OWN - NLM
STAT- MEDLINE
DCOM- 20170531
LR  - 20210909
IS  - 1097-0142 (Electronic)
IS  - 0008-543X (Print)
IS  - 0008-543X (Linking)
VI  - 123
IP  - 6
DP  - 2017 May 15
TI  - MET tyrosine kinase receptor expression and amplification as prognostic 
      biomarkers of survival in gastroesophageal adenocarcinoma.
PG  - 1061-1070
LID - 10.1002/cncr.30437 [doi]
AB  - BACKGROUND: MET gene amplification and Met protein overexpression may be 
      associated with a poor prognosis. The MET/Met status is typically determined with 
      fluorescence in situ hybridization (FISH) and immunohistochemistry (IHC), 
      respectively. Targeted proteomics uses mass spectrometry-based selected reaction 
      monitoring (SRM) to accurately quantitate Met expression. FISH, IHC, and SRM 
      analyses were compared to characterize the prognostic value of MET/Met in 
      gastroesophageal adenocarcinoma (GEC). METHODS: Samples from 447 GEC patients 
      were analyzed for MET gene amplification (FISH) and Met protein expression (IHC 
      and SRM). Cox proportional hazards models and Kaplan-Meier estimates were applied 
      to explore relations between Met, overall survival (OS), and 
      clinical/pathological characteristics. Spearman's rank coefficient was used to 
      assess the correlation between parameters. RESULTS: Patients with MET-amplified 
      tumors had worse OS when: the MET/centromere enumeration probe for chromosome 7 
      FISH ratio was >/= 2 (hazard ratio [HR], 3.13; 95% confidence interval [CI], 
      1.84-5.33), the MET gene copy number was >/=5 (HR, 2.51; 95% CI, 1.45-4.34), 
      or >/= 10% of the cells had >/=15 copies (HR, 4.28; 95% CI, 2.18-8.39). Similar 
      observations were made with Met protein overexpression by IHC (>/=1 + intensity 
      in >/= 25% of the tumor cell membrane: HR, 1.39; 95% CI, 1.04-1.86) or SRM (>/=400 
      amol/mug: HR, 1.76; 95% CI, 1.06-2.90). A significant correlation was observed 
      between MET FISH/Met IHC, MET FISH/Met SRM, and Met IHC/Met SRM; only MET FISH 
      and Met SRM were independent negative prognostic biomarkers in multivariate 
      analyses. CONCLUSIONS: MET amplification and overexpression, assessed by multiple 
      methods, were associated with a worse prognosis in univariate analyses. However, 
      only MET amplification by FISH and Met expression by SRM were independent 
      prognostic biomarkers. Compared with IHC, SRM may provide an added benefit for 
      informed decisions about Met-targeted therapy. Cancer 2017;123:1061-70. (c) 2016 
      American Cancer Society.
CI  - (c) 2016 The Authors. Cancer published by Wiley Periodicals, Inc. on behalf of 
      American Cancer Society.
FAU - Catenacci, Daniel V T
AU  - Catenacci DV
AD  - Section of Hematology/Oncology, Department of Medicine, University of Chicago, 
      Chicago, Illinois.
FAU - Ang, Agnes
AU  - Ang A
AD  - Amgen, Inc, Thousand Oaks, California.
FAU - Liao, Wei-Li
AU  - Liao WL
AD  - NantOmics, LLC, Rockville, Maryland.
FAU - Shen, Jing
AU  - Shen J
AD  - Amgen, Inc, Thousand Oaks, California.
FAU - O'Day, Emily
AU  - O'Day E
AD  - Section of Hematology/Oncology, Department of Medicine, University of Chicago, 
      Chicago, Illinois.
FAU - Loberg, Robert D
AU  - Loberg RD
AD  - Amgen, Inc, Thousand Oaks, California.
FAU - Cecchi, Fabiola
AU  - Cecchi F
AD  - NantOmics, LLC, Rockville, Maryland.
FAU - Hembrough, Todd
AU  - Hembrough T
AD  - NantOmics, LLC, Rockville, Maryland.
FAU - Ruzzo, Annamaria
AU  - Ruzzo A
AD  - Department of Biomolecular Science, University of Urbino, Urbino, Italy.
FAU - Graziano, Francesco
AU  - Graziano F
AD  - Department of Onco-Hematology, Azienda Ospedali Riuniti Marche Nord, Pesaro, 
      Italy.
LA  - eng
GR  - K12 CA139160/CA/NCI NIH HHS/United States
GR  - K23 CA178203/CA/NCI NIH HHS/United States
GR  - P30 CA014599/CA/NCI NIH HHS/United States
PT  - Journal Article
PT  - Research Support, N.I.H., Extramural
PT  - Research Support, Non-U.S. Gov't
DEP - 20161207
PL  - United States
TA  - Cancer
JT  - Cancer
JID - 0374236
RN  - 0 (Biomarkers, Tumor)
RN  - EC 2.7.10.1 (Proto-Oncogene Proteins c-met)
SB  - IM
MH  - Adenocarcinoma/*genetics/*mortality
MH  - Biomarkers, Tumor
MH  - Esophageal Neoplasms/*genetics/*mortality
MH  - *Gene Amplification
MH  - *Gene Expression
MH  - Humans
MH  - Immunohistochemistry
MH  - In Situ Hybridization, Fluorescence
MH  - Mass Spectrometry
MH  - Prognosis
MH  - Proportional Hazards Models
MH  - Proto-Oncogene Proteins c-met/*genetics
MH  - Stomach Neoplasms/*genetics/*mortality
PMC - PMC5339041
MID - NIHMS825919
OTO - NOTNLM
OT  - MET tyrosine kinase
OT  - fluorescence in situ hybridization
OT  - gastroesophageal adenocarcinoma
OT  - gene amplification
OT  - immunohistochemistry
OT  - negative prognostic biomarker
OT  - protein overexpression
OT  - selected reaction monitoring mass spectrometry
EDAT- 2016/12/08 06:00
MHDA- 2017/06/01 06:00
PMCR- 2017/03/13
CRDT- 2016/12/08 06:00
PHST- 2016/07/18 00:00 [received]
PHST- 2016/09/14 00:00 [revised]
PHST- 2016/10/05 00:00 [accepted]
PHST- 2016/12/08 06:00 [pubmed]
PHST- 2017/06/01 06:00 [medline]
PHST- 2016/12/08 06:00 [entrez]
PHST- 2017/03/13 00:00 [pmc-release]
AID - CNCR30437 [pii]
AID - 10.1002/cncr.30437 [doi]
PST - ppublish
SO  - Cancer. 2017 May 15;123(6):1061-1070. doi: 10.1002/cncr.30437. Epub 2016 Dec 7.