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Complementary utility of targeted next-generation sequencing and immunohistochemistry panels as a screening platform to select targeted therapy for advanced gastric cancer

 Hyo Song Kim  ;  Hanna Lee  ;  Su-Jin Shin  ;  Seung-Hoon Beom  ;  Minkyu Jung  ;  Sujin Bae  ;  Eun Young Lee  ;  Kyu Hyun Park  ;  Yoon Young Choi  ;  Taeil Son  ;  Hyoung-Il Kim  ;  Jae-Ho Cheong  ;  Woo Jin Hyung  ;  Jun Chul Park  ;  Sung Kwan Shin  ;  Sang Kil Lee  ;  Yong Chan Lee  ;  Woong Sub Koom  ;  Joon Seok Lim  ;  Hyun Cheol Chung  ;  Sung Hoon Noh  ;  Sun Young Rha  ;  Hyunki Kim  ;  Soonmyung Paik 
 Oncotarget, Vol.8(24) : 38389, 2017 
Journal Title
Issue Date
Adult ; Aged ; Biomarkers ; Tumor/analysis ; Biomarkers ; Tumor/genetics ; Feasibility Studies ; Female ; High-Throughput Nucleotide Sequencing/methods ; Humans ; Immunohistochemistry/methods ; Kaplan-Meier Estimate ; Male ; Middle Aged ; Molecular Targeted Therapy/methods ; Stomach Neoplasms/drug therapy ; Stomach Neoplasms/genetics ; Stomach Neoplasms/mortality
gastric cancer ; immunohistochemistry ; matched therapy ; molecular subtypes ; next-generation sequencing
We tested the clinical utility of combined profiling of Ion Torrent PGM based next-generation sequencing (NGS) and immunohistochemistry (IHC) for assignment to molecularly targeted therapies. A consecutive cohort of 93 patients with advanced/metastatic GC who underwent palliative chemotherapy between March and December 2015 were prospectively enrolled. Formalin fixed paraffin embedded tumor biopsy specimens were subjected to a 10 GC panels [Epstein Barr virus encoding RNA in-situ hybridization, IHC for mismatch repair proteins (MMR; MLH1, PMS2, MSH2, and MSH6), receptor tyrosine kinases (HER2, EGFR, and MET), PTEN, and p53 protein], and a commercial targeted NGS panel of 52 genes (Oncomine Focus Assay). Treatment was based on availability of targeted agents at the time of molecular diagnosis. Among the 81 cases with available tumor samples, complete NGS and IHC profiles were successfully achieved in 66 cases (81.5%); only IHC results were available for 15 cases. Eight cases received matched therapy based on sequencing results; ERBB2 amplification, trastuzumab (n = 4); PIK3CA mutation, Akt inhibitor (n = 2); and FGFR2 amplification, FGFR2b inhibitor (n = 2). Eleven cases received matched therapy based on IHC; ERBB2 positivity, trastuzumab (n = 5); PTEN loss (n = 2), PI3Kβ inhibitor; MMR deficiency (n = 2), PD-1 inhibitor; and EGFR positivity (n = 2), pan-ERBB inhibitor. A total of 19 (23.5%) and 62 (76.5%) cases were treated with matched and non-matched therapy, respectively. Matched therapy had significantly higher overall response rate than non-matched therapy (55.6% vs 13.1%, P = 0.001). NGS and IHC markers provide complementary utility in identifying patients who may benefit from targeted therapies.
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1. College of Medicine (의과대학) > Dept. of Radiation Oncology (방사선종양학교실) > 1. Journal Papers
1. College of Medicine (의과대학) > Dept. of Pathology (병리학교실) > 1. Journal Papers
1. College of Medicine (의과대학) > Dept. of Surgery (외과학교실) > 1. Journal Papers
1. College of Medicine (의과대학) > Dept. of Internal Medicine (내과학교실) > 1. Journal Papers
1. College of Medicine (의과대학) > Yonsei Biomedical Research Center (연세의생명연구원) > 1. Journal Papers
1. College of Medicine (의과대학) > BioMedical Science Institute (의생명과학부) > 1. Journal Papers
1. College of Medicine (의과대학) > Dept. of Radiology (영상의학교실) > 1. Journal Papers
Yonsei Authors
금웅섭(Koom, Woong Sub) ORCID logo https://orcid.org/0000-0002-9435-7750
김현기(Kim, Hyunki) ORCID logo https://orcid.org/0000-0003-2292-5584
김형일(Kim, Hyoung Il) ORCID logo https://orcid.org/0000-0002-6134-4523
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
박규현(Park, Kyu Hyun)
박준철(Park, Jun Chul) ORCID logo https://orcid.org/0000-0001-8018-0010
배수진(Bae, Sujin)
백순명(Paik, Soon Myung) ORCID logo https://orcid.org/0000-0001-9688-6480
범승훈(Beom, Seung Hoon) ORCID logo https://orcid.org/0000-0001-7036-3753
손태일(Son, Tae Il) ORCID logo https://orcid.org/0000-0002-0327-5224
신성관(Shin, Sung Kwan)
이상길(Lee, Sang Kil) ORCID logo https://orcid.org/0000-0002-0721-0364
이용찬(Lee, Yong Chan)
이은영(Lee, Eun Young)
이한나(Lee, Hanna)
임준석(Lim, Joon Seok) ORCID logo https://orcid.org/0000-0002-0334-5042
정민규(Jung, Min Kyu) ORCID logo https://orcid.org/0000-0001-8281-3387
정재호(Cheong, Jae Ho) ORCID logo https://orcid.org/0000-0002-1703-1781
정현철(Chung, Hyun Cheol) ORCID logo https://orcid.org/0000-0002-0920-9471
최윤영(Choi, Yoon Young) ORCID logo https://orcid.org/0000-0002-2179-7851
형우진(Hyung, Woo Jin) ORCID logo https://orcid.org/0000-0002-8593-9214
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