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 ChungSung Hoon Noh, Sun Young Rha, Hyunki Kim, Soonmyung Paik

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Abstract

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.

Original languageEnglish
Pages (from-to)38389-38398
Number of pages10
JournalOncotarget
Volume8
Issue number24
DOIs
Publication statusPublished - 2017 Jan 1

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Stomach Neoplasms
Immunohistochemistry
Therapeutics
Receptor, Fibroblast Growth Factor, Type 2
PTEN Phosphohydrolase
Proto-Oncogene Proteins c-met
DNA Mismatch Repair
Human Herpesvirus 4
Phosphatidylinositol 3-Kinases
Paraffin
Formaldehyde
In Situ Hybridization
Neoplasms
RNA
Ions
Biopsy
Drug Therapy
Mutation
Genes

All Science Journal Classification (ASJC) codes

  • Oncology

Cite this

Kim, Hyo Song ; Lee, Hanna ; Shin, Su Jin ; Beom, Seung Hoon ; Jung, Minkyu ; Bae, Sujin ; Lee, Eun Young ; Park, Kyu Hyun ; Choi, Yoon Young ; Son, Taeil ; Kim, Hyoung Il ; Cheong, Jae Ho ; Hyung, Woo Jin ; Park, Jun Chul ; Shin, Sung Kwan ; Lee, Sang Kil ; Lee, Yong Chan ; Koom, Woong Sub ; Lim, Joon Seok ; Chung, Hyun Cheol ; Noh, Sung Hoon ; Rha, Sun Young ; Kim, Hyunki ; Paik, Soonmyung. / Complementary utility of targeted next-generation sequencing and immunohistochemistry panels as a screening platform to select targeted therapy for advanced gastric cancer. In: Oncotarget. 2017 ; Vol. 8, No. 24. pp. 38389-38398.
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abstract = "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.",
author = "Kim, {Hyo Song} and Hanna Lee and Shin, {Su Jin} and Beom, {Seung Hoon} and Minkyu Jung and Sujin Bae and Lee, {Eun Young} and Park, {Kyu Hyun} and Choi, {Yoon Young} and Taeil Son and Kim, {Hyoung Il} and Cheong, {Jae Ho} and Hyung, {Woo Jin} and Park, {Jun Chul} and Shin, {Sung Kwan} and Lee, {Sang Kil} and Lee, {Yong Chan} and Koom, {Woong Sub} and Lim, {Joon Seok} and Chung, {Hyun Cheol} and Noh, {Sung Hoon} and Rha, {Sun Young} and Hyunki Kim and Soonmyung Paik",
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Kim, HS, Lee, H, Shin, SJ, Beom, SH, Jung, M, Bae, S, Lee, EY, Park, KH, Choi, YY, Son, T, Kim, HI, Cheong, JH, Hyung, WJ, Park, JC, Shin, SK, Lee, SK, Lee, YC, Koom, WS, Lim, JS, Chung, HC, Noh, SH, Rha, SY, Kim, H & Paik, S 2017, 'Complementary utility of targeted next-generation sequencing and immunohistochemistry panels as a screening platform to select targeted therapy for advanced gastric cancer', Oncotarget, vol. 8, no. 24, pp. 38389-38398. https://doi.org/10.18632/oncotarget.16409

Complementary utility of targeted next-generation sequencing and immunohistochemistry panels as a screening platform to select targeted therapy for advanced gastric cancer. / Kim, Hyo Song; Lee, Hanna; Shin, Su Jin; Beom, Seung Hoon; Jung, Minkyu; Bae, Sujin; Lee, Eun Young; Park, Kyu Hyun; Choi, Yoon Young; Son, Taeil; Kim, Hyoung Il; Cheong, Jae Ho; Hyung, Woo Jin; Park, Jun Chul; Shin, Sung Kwan; Lee, Sang Kil; Lee, Yong Chan; Koom, Woong Sub; Lim, Joon Seok; Chung, Hyun Cheol; Noh, Sung Hoon; Rha, Sun Young; Kim, Hyunki; Paik, Soonmyung.

In: Oncotarget, Vol. 8, No. 24, 01.01.2017, p. 38389-38398.

Research output: Contribution to journalArticle

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T1 - Complementary utility of targeted next-generation sequencing and immunohistochemistry panels as a screening platform to select targeted therapy for advanced gastric cancer

AU - Kim, Hyo Song

AU - Lee, Hanna

AU - Shin, Su Jin

AU - Beom, Seung Hoon

AU - Jung, Minkyu

AU - Bae, Sujin

AU - Lee, Eun Young

AU - Park, Kyu Hyun

AU - Choi, Yoon Young

AU - Son, Taeil

AU - Kim, Hyoung Il

AU - Cheong, Jae Ho

AU - Hyung, Woo Jin

AU - Park, Jun Chul

AU - Shin, Sung Kwan

AU - Lee, Sang Kil

AU - Lee, Yong Chan

AU - Koom, Woong Sub

AU - Lim, Joon Seok

AU - Chung, Hyun Cheol

AU - Noh, Sung Hoon

AU - Rha, Sun Young

AU - Kim, Hyunki

AU - Paik, Soonmyung

PY - 2017/1/1

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N2 - 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.

AB - 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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