Molecular profiling in gastric cancer: Examining potential targets for chemotherapy

John T. Miura, Fabian M. Johnston, James Thomas, Ben George, Dan Eastwood, Susan Tsai, Kathleen K. Christians, Kiran K. Turaga, T. Clark Gamblin

Research output: Contribution to journalArticle

Abstract

Background and Objectives: Current NCCN guidelines recommend epirubicin (E), cisplatin (C), and 5-fluorouracil (F) as a first-line therapeutic approach for operable gastric adenocarcinoma (GC). Molecular profiling (MP) was used to evaluate the expression of chemotherapy targeted biomarkers associated with ECF therapy and other first-line cytotoxic regimens for GC. Methods: GC specimens were analyzed by immunohistochemistry (IHC) for TOP2A, TS, ERCC1, PGP, and TOPO1 expression (Caris Life Sciences, Phoenix, AZ) from 2009 to 2012. Results: A total of 230 GC specimens were analyzed. The median age of patients was 61 (IQR: 50-72) years with the majority being male (n = 139, 60%). IHC actionable targets included: 60% (n = 138) high TOP2A, 55% (n = 127) negative ERCC1, and 63% (n = 145) negative TS, indicating potential benefit from E, C, and F, respectively. Simultaneous expression analysis demonstrated only 24% (n = 55) of patients had gene expression levels that suggested uniform sensitivity to ECF. Biomarker results of 6.5% (n = 15) of patients revealed a potential complete lack of sensitivity to first-line ECF. Conclusions: MP of GC has the potential to define patients who would derive the greatest benefit from current therapies. Prospective controlled studies are required to validate the role of biomarkers in the management of GC patients.

Original languageEnglish (US)
Pages (from-to)302-306
Number of pages5
JournalJournal of Surgical Oncology
Volume110
Issue number3
DOIs
StatePublished - Sep 2014

Keywords

  • adenocarcinoma
  • cancer
  • chemotherapy
  • gastric
  • molecular profiling

ASJC Scopus subject areas

  • Surgery
  • Oncology

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  • Cite this

    Miura, J. T., Johnston, F. M., Thomas, J., George, B., Eastwood, D., Tsai, S., Christians, K. K., Turaga, K. K., & Gamblin, T. C. (2014). Molecular profiling in gastric cancer: Examining potential targets for chemotherapy. Journal of Surgical Oncology, 110(3), 302-306. https://doi.org/10.1002/jso.23639