Molecular profiling in gastric cancer: examining potential targets for chemotherapy.
OBJECTIVE
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.
Division of Surgical Oncology, Department of Surgery, Medical College of Wisconsin, Milwaukee, Wisconsin.
John T
JT
Miura
Fabian M
FM
Johnston
James
J
Thomas
Ben
B
George
Dan
D
Eastwood
Susan
S
Tsai
Kathleen K
KK
Christians
Kiran K
KK
Turaga
T Clark
TC
Gamblin
D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1 / Q000378:metabolism; D000230:Adenocarcinoma / Q000188:drug therapy* / Q000378:metabolism*; D000368:Aged; D000951:Antigens, Neoplasm / Q000378:metabolism; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D015415:Biomarkers / Q000378:metabolism; D002945:Cisplatin / Q000008:administration & dosage; D004264:DNA Topoisomerases, Type I / Q000378:metabolism; D004250:DNA Topoisomerases, Type II / Q000378:metabolism; D004268:DNA-Binding Proteins / Q000378:metabolism; D019008:Drug Resistance, Neoplasm; D004720:Endonucleases / Q000378:metabolism; D015251:Epirubicin / Q000008:administration & dosage; D005260:Female; D005472:Fluorouracil / Q000008:administration & dosage; D006801:Humans; D007150:Immunohistochemistry; D008297:Male; D008875:Middle Aged; D009363:Neoplasm Proteins / Q000378:metabolism*; D000075223:Poly-ADP-Ribose Binding Proteins; D013274:Stomach Neoplasms / Q000188:drug therapy* / Q000378:metabolism*; D013940:Thymidylate Synthase / Q000378:metabolism
D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1; D000951:Antigens, Neoplasm; D015415:Biomarkers; D004268:DNA-Binding Proteins; D009363:Neoplasm Proteins; D000075223:Poly-ADP-Ribose Binding Proteins; D015251:Epirubicin; D013940:Thymidylate Synthase; C071447:ERCC1 protein, human; D004720:Endonucleases; D004264:DNA Topoisomerases, Type I; D004250:DNA Topoisomerases, Type II; C000618811:TOP2A protein, human; D002945:Cisplatin; D005472:Fluorouracil
adenocarcinoma; cancer; chemotherapy; gastric; molecular profiling