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

• Published in: Clinical & translational oncology 2015-06, Vol.17 (6), p.462-468
• Main Authors: Kim, S. T., Do, I.-G., Lee, J., Sohn, I., Kim, K.-M., Kang, W. K.
• Format: Article
• Language: English
• Subjects: Adult; Aged; Antineoplastic Combined Chemotherapy Protocols - therapeutic use; Area Under Curve; Capecitabine - administration & dosage; Everolimus - administration & dosage; Female; Genes, erbB-1 - genetics; Genes, erbB-2 - genetics; High-Throughput Nucleotide Sequencing - methods; Humans; Immunohistochemistry; In Situ Hybridization, Fluorescence; Male; Medicine; Medicine & Public Health; Middle Aged; Oncology; Proto-Oncogene Proteins c-met - genetics; Research Article; ROC Curve; Salvage Therapy - methods; Sensitivity and Specificity; Sequence Analysis, RNA - methods; Stomach Neoplasms - drug therapy; Stomach Neoplasms - genetics
• ISSN: 1699-048X; 1699-3055
• DOI: 10.1007/s12094-014-1258-7

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.