Molecular profiling in gastric cancer: examining potential targets for chemotherapy.

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.

journal_name

J Surg Oncol

authors

Miura JT,Johnston FM,Thomas J,George B,Eastwood D,Tsai S,Christians KK,Turaga KK,Gamblin TC

doi

10.1002/jso.23639

subject

Has Abstract

pub_date

2014-09-01 00:00:00

pages

302-6

issue

3

eissn

0022-4790

issn

1096-9098

journal_volume

110

pub_type

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