MET in gastric carcinomas: comparison between protein expression and gene copy number and impact on clinical outcome.
BACKGROUND
The aim of this study was to compare gene copy number (GCN) and protein expression of MET and to evaluate their prognostic roles in gastric carcinomas.


METHODS
MET protein expression and gene amplification (GA) status were determined by immunohistochemistry (IHC) and silver in-situ hybridisation (SISH), respectively, in a large series of gastric carcinoma.


RESULTS
Protein overexpression was observed in 104 of 438 cases, with IHC 2+ in 94 and IHC 3+ in 10, and high polysomy of chromosome 7 and GA were found in 61 and 13 of 381, respectively. Direct comparison revealed a significant correlation between high level of protein expression and increased GCN. All cases with GA showed protein overexpression. Furthermore, all with IHC 3+ showed GA except 1, even which could be categorised as GA according to the ASCO/CAP guideline for human epidermal growth factor receptor 2 assessment. IHC 3+ and GA were significantly associated with poor prognosis.


CONCLUSIONS
MET IHC reflects well on GA, and therefore, it could be a primary screening test for patient selection for anti-MET therapy if GA is a major determinant of drug responsiveness. Also, the prognostic role of MET indicates that anti-MET therapy is a very promising modality in adjuvant treatment for gastric cancer.
Department of Pathology, Seoul National University Hospital, 28 Yeongeon-dong, Jongno-gu, Seoul 110-799, Korea.
H E
HE
Lee
M A
MA
Kim
H S
HS
Lee
E-J
EJ
Jung
H-K
HK
Yang
B L
BL
Lee
Y-J
YJ
Bang
W H
WH
Kim
D000368:Aged; D002277:Carcinoma / Q000235:genetics* / Q000378:metabolism; D002886:Chromosomes, Human, Pair 17; D015331:Cohort Studies; D005260:Female; D005500:Follow-Up Studies; D005784:Gene Amplification; D018628:Gene Dosage; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D007150:Immunohistochemistry / Q000379:methods; D008297:Male; D008875:Middle Aged; D011379:Prognosis; D019859:Proto-Oncogene Proteins c-met / Q000096:biosynthesis / Q000235:genetics*; D018719:Erb-b2 Receptor Tyrosine Kinases / Q000235:genetics; D012189:Retrospective Studies; D013274:Stomach Neoplasms / Q000235:genetics* / Q000378:metabolism
D019859:Proto-Oncogene Proteins c-met; D018719:Erb-b2 Receptor Tyrosine Kinases; C491743:MET protein, human