Faculty Collaboration Database

Molecular profiling in gastric cancer: examining potential targets for chemotherapy. J Surg Oncol 2014 Sep;110(3):302-6

Date

05/23/2014

Pubmed ID

24844210

DOI

10.1002/jso.23639

Scopus ID

2-s2.0-84905367494 (requires institutional sign-in at Scopus site)   9 Citations

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.

Author List

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

Authors

Kathleen K. Christians MD Professor in the Surgery department at Medical College of Wisconsin
Thomas Clark Gamblin MD Professor in the Surgery department at Medical College of Wisconsin
Ben George MD Professor in the Medicine department at Medical College of Wisconsin
James P. Thomas MD, PhD Professor in the Medicine department at Medical College of Wisconsin

MESH terms used to index this publication - Major topics in bold

Adenocarcinoma
Aged
Antigens, Neoplasm
Antineoplastic Combined Chemotherapy Protocols
Biomarkers
Cisplatin
DNA Topoisomerases, Type I
DNA Topoisomerases, Type II
DNA-Binding Proteins
Drug Resistance, Neoplasm
Endonucleases
Epirubicin
Female
Fluorouracil
Humans
Immunohistochemistry
Male
Middle Aged
Neoplasm Proteins
Poly-ADP-Ribose Binding Proteins
Stomach Neoplasms
Thymidylate Synthase