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Receptor tyrosine kinase amplified gastric cancer: Clinicopathologic characteristics and proposed screening algorithm

 Cheol Keun Park  ;  Ji Soo Park  ;  Hyo Song Kim  ;  Sun Young Rha  ;  Woo Jin Hyung  ;  Jae-Ho Cheong  ;  Sung Hoon Noh  ;  Sang Kil Lee  ;  Yong Chan Lee  ;  Yong-min Huh  ;  Hyunki Kim 
 Oncotarget, Vol.7(44) : 72099-72112, 2016 
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Although targeted therapy for receptor tyrosine kinases (RTKs) of advanced gastric cancers (AGCs) has been in the spotlight, guidelines for the identification of RTK-amplified gastric cancers (RA-GCs) have not been established. In this study, we investigate clinicopathologic characteristics of RA-GCs and propose a screening algorithm for their identification. We performed immunohistochemistry (IHC) for MLH1, MSH2, PMS2, MSH6, key RTKs (EGFR, HER2, MET), and p53, in situ hybridization for Epstein-Barr virus encoding RNA, and silver in situ hybridization (SISH) for EGFR, HER2, and MET using tissue microarrays of 993 AGCs. On IHC, 157 (15.8%) 61, (6.15%), and 85 (8.56%) out of 993 cases scored 2+ or 3+ for EGFR, HER2, and MET, respectively. On SISH, 31.2% (49/157), 80.3% (49/61), and 30.6% (26/85) of 2+ or 3+ cases on IHC showed amplification of the corresponding genes. Of the 993 cases, 104 were classified as RA-GCs. RA-GC status correlated with older age (P < 0.001), differentiated histology (P = 0.001), intestinal or mixed type by Lauren classification (P < 0.001), lymphovascular invasion (P = 0.026), and mutant-pattern of p53 (P < 0.001). The cases were divided into four subgroups using two classification systems, putative molecular classification and histologic-molecular classification, based on Lauren classification, IHC, and SISH results. The histologic-molecular classification showed higher sensitivity for identification of RA-GCs and predicted patient prognosis better than the putative molecular classification. In conclusion, RA-GCs show unique clinicopathologic features. The proposed algorithm based on histologic-molecular classification can be applied to select candidates for genetic examination and targeted therapy.
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1. College of Medicine (의과대학) > Dept. of Pathology (병리학교실) > 1. Journal Papers
1. College of Medicine (의과대학) > Dept. of Internal Medicine (내과학교실) > 1. Journal Papers
1. College of Medicine (의과대학) > Dept. of Surgery (외과학교실) > 1. Journal Papers
1. College of Medicine (의과대학) > Dept. of Radiology (영상의학교실) > 1. Journal Papers
Yonsei Authors
김현기(Kim, Hyunki) ORCID logo https://orcid.org/0000-0003-2292-5584
김효송(Kim, Hyo Song) ORCID logo https://orcid.org/0000-0002-0625-9828
노성훈(Noh, Sung Hoon) ORCID logo https://orcid.org/0000-0003-4386-6886
라선영(Rha, Sun Young) ORCID logo https://orcid.org/0000-0002-2512-4531
박지수(Park, Ji Soo) ORCID logo https://orcid.org/0000-0002-0023-7740
이상길(Lee, Sang Kil) ORCID logo https://orcid.org/0000-0002-0721-0364
이용찬(Lee, Yong Chan)
정재호(Cheong, Jae Ho) ORCID logo https://orcid.org/0000-0002-1703-1781
허용민(Huh, Yong Min) ORCID logo https://orcid.org/0000-0002-9831-4475
형우진(Hyung, Woo Jin) ORCID logo https://orcid.org/0000-0002-8593-9214
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