Complementary utility of targeted next-generation sequencing and immunohistochemistry panels as a screening platform to select targeted therapy for advanced gastric cancer
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Hyo Song Kim1,*, Hanna Lee2,*, Su-Jin Shin3,*, Seung-Hoon Beom1, Minkyu Jung1, Sujin Bae2, Eun Young Lee2, Kyu Hyun Park4, Yoon Young Choi5, Taeil Son5, Hyoung-Il Kim5, Jae-Ho Cheong5, Woo Jin Hyung5, Jun Chul Park6, Sung Kwan Shin6, Sang Kil Lee6, Yong Chan Lee6, Woong Sub Koom7, Joon Seok Lim8, Hyun Cheol Chung1,4, Sung Hoon Noh5, Sun Young Rha1,4, Hyunki Kim3, Soonmyung Paik2
1Division of Medical Oncology, Department of Internal Medicine, Yonsei University College of Medicine, Seoul, Republic of Korea
2Severance Biomedical Science Institute, Yonsei University College of Medicine, Seoul, Republic of Korea
3Hanyang University, College of Medicine, Seoul, Republic of Korea
4Cancer Metastasis Research Center, Song Dang Institute for Cancer Research, Yonsei University College of Medicine, Seoul, Republic of Korea
5Department of Surgery, Yonsei University College of Medicine, Seoul, Republic of Korea
6Division of Gastroenterology, Department of Internal Medicine, Yonsei University College of Medicine, Seoul, Republic of Korea
7Department of Radiation Oncology, Yonsei University College of Medicine, Seoul, Republic of Korea
8Department of Radiology, Yonsei University College of Medicine, Seoul, Republic of Korea
*These authors contributed equally to this work as co-first authors
Soonmyung Paik, email: [email protected]
Hyunki Kim, email: [email protected]
Sun Young Rha, email: [email protected] yuhs.ac
Keywords: gastric cancer, molecular subtypes, next-generation sequencing, immunohistochemistry, matched therapy
Received: November 23, 2016 Accepted: February 20, 2017 Published: March 21, 2017
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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