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Molecular profiling in gastric cancer: Examining potential targets for chemotherapy
Author(s) -
Miura John T.,
Johnston Fabian M.,
Thomas James,
George Ben,
Eastwood Dan,
Tsai Susan,
Christians Kathleen K.,
Turaga Kiran K.,
Gamblin T. Clark
Publication year - 2014
Publication title -
journal of surgical oncology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.201
H-Index - 111
eISSN - 1096-9098
pISSN - 0022-4790
DOI - 10.1002/jso.23639
Subject(s) - ercc1 , medicine , oncology , epirubicin , immunohistochemistry , biomarker , cisplatin , chemotherapy , cancer , gastroenterology , breast cancer , gene , dna repair , biochemistry , nucleotide excision repair , chemistry
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. J. Surg. Oncol. 2014 110:302–306 . © 2014 Wiley Periodicals, Inc.