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Concurrent MET copy number gain and KRAS mutation is a poor prognostic factor in pancreatobiliary subtype ampullary cancers

Title
Concurrent MET copy number gain and KRAS mutation is a poor prognostic factor in pancreatobiliary subtype ampullary cancers
Author
민경환
Keywords
Ampulla of Vater; Adenocarcinoma; MET; HGF; Immunohistochemistry; Silver in situ hybridization
Issue Date
2017-04
Publisher
ELSEVIER GMBH
Citation
PATHOLOGY RESEARCH AND PRACTICE, v. 213, no. 4, page. 381-388
Abstract
Hepatocyte growth factor (HGF) and MET are candidates of targeted therapies for cancer patients. Although MET and HGF are commonly expressed in biliary tract cancers, their expression and gene copy number status and their association with KRAS mutations have not been investigated in pancreatobiliary-type ampullary adenocarcinomas (A-ACs), one of the aggressive periampullary cancers. MET and HGF expressions and MET copy number status were examined by performing immunohistochemistry (IHC) and silver in situ hybridization (SISH) in 62 surgically resected, paraffin-embedded tumors, respectively. High MET and HGF protein expressions were detected in 24 (38.7%) and 15 (24.2%) tumors. High MET expression was associated with KRAS mutation. However, there were no associations of high MET/HGF expression alone with other clinicopathological feature or survival. MET SISH positivity was detected in 19 tumors (30.6%), where 84.2% were due to high trisomy or polysomy and only 3 cases (15.8%) were MET gene amplification. The overall MET protein overexpression was well correlated with METSISH positivity. The concurrent MET SISH positivity and KRAS mutation, not each alone, was an independent poor prognostic factor of disease-free survival only in pancreatobiliary subtype of A-ACs, but not in intestinal subtype.Concurrent MET SISH positivity and KRAS mutation may predict a high risk of recurrence in pancreatobiliary subtype of A-ACs, indicating those markers could be potent candidates for a new therapeutic target in this cancer type. MET IHC can be used as a reliable tool screening for MET copy number status in ampullary cancers. (C) 2017 Elsevier GmbH. All rights reserved.
URI
https://www.sciencedirect.com/science/article/pii/S0344033816302667?via%3Dihubhttp://repository.hanyang.ac.kr/handle/20.500.11754/113857
ISSN
0344-0338
DOI
10.1016/j.prp.2017.01.004
Appears in Collections:
COLLEGE OF MEDICINE[S](의과대학) > MEDICINE(의학과) > Articles
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