Molecular profiling in gastric cancer: Examining potential targets for chemotherapy

John T. Miura, Fabian 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 - 2014
Externally publishedYes

Fingerprint

Stomach Neoplasms
Stomach
Adenocarcinoma
Drug Therapy
Biomarkers
Immunohistochemistry
Epirubicin
Biological Science Disciplines
Fluorouracil
Cisplatin
Therapeutics
Prospective Studies
Guidelines
Gene Expression

Keywords

  • adenocarcinoma
  • cancer
  • chemotherapy
  • gastric
  • molecular profiling

ASJC Scopus subject areas

  • Surgery
  • Oncology

Cite this

Miura, J. T., Johnston, F., Thomas, J., George, B., Eastwood, D., Tsai, S., ... 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

Molecular profiling in gastric cancer : Examining potential targets for chemotherapy. / Miura, John T.; Johnston, Fabian; Thomas, James; George, Ben; Eastwood, Dan; Tsai, Susan; Christians, Kathleen K.; Turaga, Kiran K.; Gamblin, T. Clark.

In: Journal of Surgical Oncology, Vol. 110, No. 3, 2014, p. 302-306.

Research output: Contribution to journalArticle

Miura, JT, Johnston, F, Thomas, J, George, B, Eastwood, D, Tsai, S, Christians, KK, Turaga, KK & Gamblin, TC 2014, 'Molecular profiling in gastric cancer: Examining potential targets for chemotherapy', Journal of Surgical Oncology, vol. 110, no. 3, pp. 302-306. https://doi.org/10.1002/jso.23639
Miura, John T. ; Johnston, Fabian ; Thomas, James ; George, Ben ; Eastwood, Dan ; Tsai, Susan ; Christians, Kathleen K. ; Turaga, Kiran K. ; Gamblin, T. Clark. / Molecular profiling in gastric cancer : Examining potential targets for chemotherapy. In: Journal of Surgical Oncology. 2014 ; Vol. 110, No. 3. pp. 302-306.
@article{f6924ac339f9417ea63bdbf50facab78,
title = "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.",
keywords = "adenocarcinoma, cancer, chemotherapy, gastric, molecular profiling",
author = "Miura, {John T.} and Fabian Johnston and James Thomas and Ben George and Dan Eastwood and Susan Tsai and Christians, {Kathleen K.} and Turaga, {Kiran K.} and Gamblin, {T. Clark}",
year = "2014",
doi = "10.1002/jso.23639",
language = "English (US)",
volume = "110",
pages = "302--306",
journal = "Journal of Surgical Oncology",
issn = "0022-4790",
publisher = "Wiley-Liss Inc.",
number = "3",

}

TY - JOUR

T1 - Molecular profiling in gastric cancer

T2 - Examining potential targets for chemotherapy

AU - Miura, John T.

AU - Johnston, Fabian

AU - Thomas, James

AU - George, Ben

AU - Eastwood, Dan

AU - Tsai, Susan

AU - Christians, Kathleen K.

AU - Turaga, Kiran K.

AU - Gamblin, T. Clark

PY - 2014

Y1 - 2014

N2 - 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.

AB - 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.

KW - adenocarcinoma

KW - cancer

KW - chemotherapy

KW - gastric

KW - molecular profiling

UR - http://www.scopus.com/inward/record.url?scp=84905367494&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=84905367494&partnerID=8YFLogxK

U2 - 10.1002/jso.23639

DO - 10.1002/jso.23639

M3 - Article

C2 - 24844210

AN - SCOPUS:84905367494

VL - 110

SP - 302

EP - 306

JO - Journal of Surgical Oncology

JF - Journal of Surgical Oncology

SN - 0022-4790

IS - 3

ER -