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01.06.2015 | Research Article

The NanoString-based multigene assay as a novel platform to screen EGFR, HER2, and MET in patients with advanced gastric cancer

verfasst von: S. T. Kim, I.-G. Do, J. Lee, I. Sohn, K.-M. Kim, W. K. Kang

Erschienen in: Clinical and Translational Oncology | Ausgabe 6/2015

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Abstract

Introduction

Molecular targets are emerging rapidly and the development of clinical tests that simultaneously screen for multiple targets has become especially important. We assessed the gene expression levels of three known targets in advanced gastric cancer, epidermal growth factor receptor (EGFR), human epidermal growth factor 2 (HER2), and N-methyl-N-nitrosoguanidine human osteosarcoma transforming gene (MET), using the nCounter® assay (NanoString Technologies, Seattle, WA, USA) and compared these results with protein overexpression, detected by immunohistochemistry, to evaluate the performance of this new technology.

Methods

We investigated 42 formalin-fixed, paraffin-embedded tumor samples from patients with gastric cancer. A NanoString-based assay containing a 522 kinase gene panel was investigated. We analyzed the correlations between immunohistochemical findings and kinase gene expression levels of EGFR, HER2 and MET to validate this assay.

Results

EGFR, HER2, and MET overexpression were observed in 7 (16.6 %), 5 (11.9 %), and 3 (7.1 %) cases, respectively. For EGFR, HER2, and MET, the concordance rates between the NanoString-based assay results and the immunohistochemistry methods were 83.3, 97.6, and 100 %, respectively. Relative to immunohistochemistry findings, the NanoString-based assay sensitivities and specificities were 85.7 and 82.8 % for EGFR, 100 and 97.2 % for HER2, and 100 and 100 % for MET, respectively.

Conclusions

We found a high concordance between immunohistochemistry- and nCounter-based assessments of EGFR, HER2, and MET in advanced gastric cancer. Judged against immunohistochemistry results, the NanoString assay had high sensitivities and high specificities. These results suggest that the nCounter assay provides a reliable, high-throughput assay to simultaneously screen for the overexpression of several target proteins.
Literatur
1.
Zurück zum Zitat Cunningham D, Jost LM, Purkalne G, Oliveira J. ESMO Minimum Clinical Recommendations for diagnosis, treatment and follow-up of gastric cancer. Ann Oncol. 2005;16(Suppl 1):i22–3.PubMed Cunningham D, Jost LM, Purkalne G, Oliveira J. ESMO Minimum Clinical Recommendations for diagnosis, treatment and follow-up of gastric cancer. Ann Oncol. 2005;16(Suppl 1):i22–3.PubMed
3.
Zurück zum Zitat Jung KW, Park S, Kong HJ, Won YJ, Lee JY, Seo HG, et al. Cancer statistics in Korea: incidence, mortality, survival, and prevalence in 2009. Cancer Res Treat. 2012;44:11–24.PubMedCentralPubMed Jung KW, Park S, Kong HJ, Won YJ, Lee JY, Seo HG, et al. Cancer statistics in Korea: incidence, mortality, survival, and prevalence in 2009. Cancer Res Treat. 2012;44:11–24.PubMedCentralPubMed
4.
Zurück zum Zitat Yoo CH, Noh SH, Shin DW, Choi SH, Min JS. Recurrence following curative resection for gastric carcinoma. Br J Surg. 2000;87:236–42.PubMed Yoo CH, Noh SH, Shin DW, Choi SH, Min JS. Recurrence following curative resection for gastric carcinoma. Br J Surg. 2000;87:236–42.PubMed
5.
Zurück zum Zitat Landry J, Tepper JE, Wood WC, Moulton EO, Koerner F, Sullinger J. Patterns of failure following curative resection of gastric carcinoma. Int J Radiat Oncol Biol Phys. 1990;19:1357–62.PubMed Landry J, Tepper JE, Wood WC, Moulton EO, Koerner F, Sullinger J. Patterns of failure following curative resection of gastric carcinoma. Int J Radiat Oncol Biol Phys. 1990;19:1357–62.PubMed
6.
Zurück zum Zitat Lim DH, Kim DY, Kang MK, Kim YI, Kang WK, Park CK, et al. Patterns of failure in gastric carcinoma after D2 gastrectomy and chemoradiotherapy: a radiation oncologist’s view. Br J Cancer. 2004;91:11–7.PubMedCentralPubMed Lim DH, Kim DY, Kang MK, Kim YI, Kang WK, Park CK, et al. Patterns of failure in gastric carcinoma after D2 gastrectomy and chemoradiotherapy: a radiation oncologist’s view. Br J Cancer. 2004;91:11–7.PubMedCentralPubMed
7.
Zurück zum Zitat Manning G, Whyte DB, Martinez R, Hunter T, Sudarsanam S. The protein kinase complement of the human genome. Science. 2002;298:1912–34.CrossRefPubMed Manning G, Whyte DB, Martinez R, Hunter T, Sudarsanam S. The protein kinase complement of the human genome. Science. 2002;298:1912–34.CrossRefPubMed
9.
Zurück zum Zitat Demetri GD, von Mehren M, Blanke CD, Van den Abbeele AD, Eisenberg B, Roberts PJ, et al. Efficacy and safety of imatinib mesylate in advanced gastrointestinal stromal tumors. N Engl J Med. 2002;347:472–80.PubMed Demetri GD, von Mehren M, Blanke CD, Van den Abbeele AD, Eisenberg B, Roberts PJ, et al. Efficacy and safety of imatinib mesylate in advanced gastrointestinal stromal tumors. N Engl J Med. 2002;347:472–80.PubMed
10.
Zurück zum Zitat Slamon DJ, Leyland-Jones B, Shak S, Fuchs H, Paton V, Bajamonde A, et al. Use of chemotherapy plus a monoclonal antibody against HER2 for metastatic breast cancer that overexpresses HER2. N Engl J Med. 2001;344:783–92.PubMed Slamon DJ, Leyland-Jones B, Shak S, Fuchs H, Paton V, Bajamonde A, et al. Use of chemotherapy plus a monoclonal antibody against HER2 for metastatic breast cancer that overexpresses HER2. N Engl J Med. 2001;344:783–92.PubMed
11.
Zurück zum Zitat Scagliotti GV, Novello S, von Pawel J. The emerging role of MET/HGF inhibitors in oncology. Cancer Treat Rev. 2013;39:793–801.PubMed Scagliotti GV, Novello S, von Pawel J. The emerging role of MET/HGF inhibitors in oncology. Cancer Treat Rev. 2013;39:793–801.PubMed
12.
Zurück zum Zitat Luis M, Tavares A, Carvalho LS, Lara-Santos L, Araujo A, de Mello RA. Personalizing therapies for gastric cancer: molecular mechanisms and novel targeted therapies. World J Gastroenterol. 2013;19:6383–97.PubMedCentralPubMed Luis M, Tavares A, Carvalho LS, Lara-Santos L, Araujo A, de Mello RA. Personalizing therapies for gastric cancer: molecular mechanisms and novel targeted therapies. World J Gastroenterol. 2013;19:6383–97.PubMedCentralPubMed
13.
Zurück zum Zitat Cunningham D, Humblet Y, Siena S, Khayat D, Bleiberg H, Santoro A, et al. Cetuximab monotherapy and cetuximab plus irinotecan in irinotecan-refractory metastatic colorectal cancer. N Engl J Med. 2004;351:337–45.PubMed Cunningham D, Humblet Y, Siena S, Khayat D, Bleiberg H, Santoro A, et al. Cetuximab monotherapy and cetuximab plus irinotecan in irinotecan-refractory metastatic colorectal cancer. N Engl J Med. 2004;351:337–45.PubMed
14.
Zurück zum Zitat Jimeno A, Hidalgo M. Blockade of epidermal growth factor receptor (EGFR) activity. Crit Rev Oncol Hematol. 2005;53:179–92.PubMed Jimeno A, Hidalgo M. Blockade of epidermal growth factor receptor (EGFR) activity. Crit Rev Oncol Hematol. 2005;53:179–92.PubMed
15.
Zurück zum Zitat Bang YJ, Van Cutsem E, Feyereislova A, Chung HC, Shen L, Sawaki A, et al. Trastuzumab in combination with chemotherapy versus chemotherapy alone for treatment of HER2-positive advanced gastric or gastro-oesophageal junction cancer (ToGA): a phase 3, open-label, randomised controlled trial. Lancet. 2010;376:687–97.PubMed Bang YJ, Van Cutsem E, Feyereislova A, Chung HC, Shen L, Sawaki A, et al. Trastuzumab in combination with chemotherapy versus chemotherapy alone for treatment of HER2-positive advanced gastric or gastro-oesophageal junction cancer (ToGA): a phase 3, open-label, randomised controlled trial. Lancet. 2010;376:687–97.PubMed
16.
Zurück zum Zitat Amemiya H, Kono K, Itakura J, Tang RF, Takahashi A, An FQ, et al. c-Met expression in gastric cancer with liver metastasis. Oncology. 2002;63:286–96.CrossRefPubMed Amemiya H, Kono K, Itakura J, Tang RF, Takahashi A, An FQ, et al. c-Met expression in gastric cancer with liver metastasis. Oncology. 2002;63:286–96.CrossRefPubMed
17.
Zurück zum Zitat Graziano F, Galluccio N, Lorenzini P, Ruzzo A, Canestrari E, D’Emidio S, et al. Genetic activation of the MET pathway and prognosis of patients with high-risk, radically resected gastric cancer. J Clin Oncol. 2011;29:4789–95.PubMed Graziano F, Galluccio N, Lorenzini P, Ruzzo A, Canestrari E, D’Emidio S, et al. Genetic activation of the MET pathway and prognosis of patients with high-risk, radically resected gastric cancer. J Clin Oncol. 2011;29:4789–95.PubMed
18.
Zurück zum Zitat Lee J, Seo JW, Jun HJ, Ki CS, Park SH, Park YS, et al. Impact of MET amplification on gastric cancer: possible roles as a novel prognostic marker and a potential therapeutic target. Oncol Rep. 2011;25:1517–24.PubMed Lee J, Seo JW, Jun HJ, Ki CS, Park SH, Park YS, et al. Impact of MET amplification on gastric cancer: possible roles as a novel prognostic marker and a potential therapeutic target. Oncol Rep. 2011;25:1517–24.PubMed
19.
Zurück zum Zitat Lennerz JK, Kwak EL, Ackerman A, Michael M, Fox SB, Bergethon K, et al. MET amplification identifies a small and aggressive subgroup of esophagogastric adenocarcinoma with evidence of responsiveness to crizotinib. J Clin Oncol. 2011;29:4803–10.PubMedCentralPubMed Lennerz JK, Kwak EL, Ackerman A, Michael M, Fox SB, Bergethon K, et al. MET amplification identifies a small and aggressive subgroup of esophagogastric adenocarcinoma with evidence of responsiveness to crizotinib. J Clin Oncol. 2011;29:4803–10.PubMedCentralPubMed
20.
Zurück zum Zitat Blumenschein GR Jr, Mills GB, Gonzalez-Angulo AM. Targeting the hepatocyte growth factor-cMET axis in cancer therapy. J Clin Oncol. 2012;30:3287–96.PubMedCentralPubMed Blumenschein GR Jr, Mills GB, Gonzalez-Angulo AM. Targeting the hepatocyte growth factor-cMET axis in cancer therapy. J Clin Oncol. 2012;30:3287–96.PubMedCentralPubMed
21.
Zurück zum Zitat Geiss GK, Bumgarner RE, Birditt B, Dahl T, Dowidar N, Dunaway DL, et al. Direct multiplexed measurement of gene expression with color-coded probe pairs. Nat Biotechnol. 2008;26:317–25.PubMed Geiss GK, Bumgarner RE, Birditt B, Dahl T, Dowidar N, Dunaway DL, et al. Direct multiplexed measurement of gene expression with color-coded probe pairs. Nat Biotechnol. 2008;26:317–25.PubMed
22.
Zurück zum Zitat Lee SJ, Lee J, Lee J, Park SH, Park JO, Park YS, et al. Phase II trial of capecitabine and everolimus (RAD001) combination in refractory gastric cancer patients. Invest New Drugs. 2013;31:1580–6.PubMed Lee SJ, Lee J, Lee J, Park SH, Park JO, Park YS, et al. Phase II trial of capecitabine and everolimus (RAD001) combination in refractory gastric cancer patients. Invest New Drugs. 2013;31:1580–6.PubMed
23.
Zurück zum Zitat Bachleitner-Hofmann T, Sun MY, Chen CT, Tang L, Song L, Zeng Z, et al. HER kinase activation confers resistance to MET tyrosine kinase inhibition in MET oncogene-addicted gastric cancer cells. Mol Cancer Ther. 2008;7:3499–508.PubMed Bachleitner-Hofmann T, Sun MY, Chen CT, Tang L, Song L, Zeng Z, et al. HER kinase activation confers resistance to MET tyrosine kinase inhibition in MET oncogene-addicted gastric cancer cells. Mol Cancer Ther. 2008;7:3499–508.PubMed
24.
Zurück zum Zitat Ruschoff J, Hanna W, Bilous M, Hofmann M, Osamura RY, Penault-Llorca F, et al. HER2 testing in gastric cancer: a practical approach. Mod Pathol. 2012;25:637–50.PubMed Ruschoff J, Hanna W, Bilous M, Hofmann M, Osamura RY, Penault-Llorca F, et al. HER2 testing in gastric cancer: a practical approach. Mod Pathol. 2012;25:637–50.PubMed
25.
Zurück zum Zitat Ha SY, Lee J, Kang SY, Do IG, Ahn S, Park JO, et al. MET overexpression assessed by new interpretation method predicts gene amplification and poor survival in advanced gastric carcinomas. Mod Pathol. 2013;26:1632–41.PubMed Ha SY, Lee J, Kang SY, Do IG, Ahn S, Park JO, et al. MET overexpression assessed by new interpretation method predicts gene amplification and poor survival in advanced gastric carcinomas. Mod Pathol. 2013;26:1632–41.PubMed
26.
Zurück zum Zitat Cho EY, Choi YL, Han JJ, Kim KM, Oh YL. Expression and amplification of Her2, EGFR and cyclin D1 in breast cancer: immunohistochemistry and chromogenic in situ hybridization. Pathol Int. 2008;58:17–25.PubMed Cho EY, Choi YL, Han JJ, Kim KM, Oh YL. Expression and amplification of Her2, EGFR and cyclin D1 in breast cancer: immunohistochemistry and chromogenic in situ hybridization. Pathol Int. 2008;58:17–25.PubMed
27.
Zurück zum Zitat Hsu JT, Chen TC, Tseng JH, Chiu CT, Liu KH, Yeh CN, et al. Impact of HER-2 overexpression/amplification on the prognosis of gastric cancer patients undergoing resection: a single-center study of 1,036 patients. Oncologist. 2011;16:1706–13.PubMedCentralPubMed Hsu JT, Chen TC, Tseng JH, Chiu CT, Liu KH, Yeh CN, et al. Impact of HER-2 overexpression/amplification on the prognosis of gastric cancer patients undergoing resection: a single-center study of 1,036 patients. Oncologist. 2011;16:1706–13.PubMedCentralPubMed
28.
Zurück zum Zitat Chen C, Yang JM, Hu TT, Xu TJ, Yan G, Hu SL, et al. Prognostic role of human epidermal growth factor receptor in gastric cancer: a systematic review and meta-analysis. Arch Med Res. 2013;44:380–9.PubMed Chen C, Yang JM, Hu TT, Xu TJ, Yan G, Hu SL, et al. Prognostic role of human epidermal growth factor receptor in gastric cancer: a systematic review and meta-analysis. Arch Med Res. 2013;44:380–9.PubMed
29.
Zurück zum Zitat Lee J, Kim S, Kim P, Liu X, Lee T, Kim KM, et al. A novel proteomics-based clinical diagnostics technology identifies heterogeneity in activated signaling pathways in gastric cancers. PLoS One. 2013;8:e54644.CrossRefPubMedCentralPubMed Lee J, Kim S, Kim P, Liu X, Lee T, Kim KM, et al. A novel proteomics-based clinical diagnostics technology identifies heterogeneity in activated signaling pathways in gastric cancers. PLoS One. 2013;8:e54644.CrossRefPubMedCentralPubMed
Metadaten
Titel
The NanoString-based multigene assay as a novel platform to screen EGFR, HER2, and MET in patients with advanced gastric cancer
verfasst von
S. T. Kim
I.-G. Do
J. Lee
I. Sohn
K.-M. Kim
W. K. Kang
Publikationsdatum
01.06.2015
Verlag
Springer Milan
Erschienen in
Clinical and Translational Oncology / Ausgabe 6/2015
Print ISSN: 1699-048X
Elektronische ISSN: 1699-3055
DOI
https://doi.org/10.1007/s12094-014-1258-7

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