568P - Tumor location and histological type related to intratumoral expression of 5-FU metabolizing enzymes in stage III colon cancer: A multicenter, pros...

Date 29 September 2014
Event ESMO 2014
Session Poster Display session
Topics Anti-Cancer Agents & Biologic Therapy
Colon Cancer
Pathology/Molecular Biology
Translational Research
Presenter Megumi Ishiguro
Citation Annals of Oncology (2014) 25 (suppl_4): iv167-iv209. 10.1093/annonc/mdu333
Authors M. Ishiguro1, E. Nakatani2, K. Kotake3, G. Nishimura4, N. Tomita5, W. Ichikawa6, K. Takahashi7, T. Watanabe8, T. Furuhata9, K. Kondo10, M. Mori11, Y. Kakeji12, A. Kanazawa13, M. Kobayashi14, M. Okajima15, I. Hyodo16, S. Tanaka17, K. Sugihara18
  • 1Translational Oncology, Tokyo Medical and Dental University, Graduate School, 113-8519 - Tokyo/JP
  • 2Department Of Statistical Analysis, Translational Research Informatics Center, Hyogo/JP
  • 3Department Of Surgery, Tochigi Cancer Center, Tochigi/JP
  • 4Surgery, Japanese Red Cross Kanazawa Hospital, Kanazawa/JP
  • 5Surgery, Hyogo College of Medicine, Hyogo/JP
  • 6Division Of Medical Oncology, Department Of Medicine, Showa University School of Medicine, Tokyo/JP
  • 7Department Of Surgery, Cancer and Infectious Diseases Center Komagome Hospital, Tokyo/JP
  • 8Department Of Surgical Oncology And Vascular Surgery, The University of Tokyo, 113-8655 - Tokyo/JP
  • 9School Of Health Science, Sapporo Medical University, JP-060-8543 - Sapporo/JP
  • 10Department Of Surgery, Nagoya Medical Center, 460-0001 - Nagoya/JP
  • 11Department Of Gastroenterological Surgery, Osaka University Graduate School of Medicine, 565-0871 - Osaka/JP
  • 12Division Of Gastrointestinal Surgery, Department Of Surgery, Kobe University, Graduate School of Medicine, Hyogo/JP
  • 13Department Of gastroenterological surgery and oncology, Kitano Hospital, Osaka/JP
  • 14Department Of Human Health And Medical Sciences, Kochi Medical School, Kochi/JP
  • 15Department Of Surgery, Hiroshima City Hospital, Hiroshima/JP
  • 16Department Of Gastroenterology, University of Tsukuba, Graduate School of Comprehensive Human Sciences, JP-305-8577 - Ibaraki/JP
  • 17Department Of Pharmacoepidemiology, Kyoto University, Graduate School of Medicine and Public Health, Kyoto/JP
  • 18Department Of Surgical Oncology, Tokyo Medical and Dental University, Graduate School, 113-8519 - Tokyo/JP

Abstract

Aim

Several oral 5-FU derivatives with different properties are used in adjuvant therapy for colon cancer in Japan. The B-CAST study is a prospective cohort study aimed efficacy prediction of 5-FU derivatives, through evaluating the intratumoral biomarker expressions and treatment outcome. We evaluated relationships between the relevant biomarker expressions and patient characteristics, as baseline analysis of the study.

Methods

The frozen tumor specimens of patients with stage III colon cancer who received postoperative adjuvant chemotherapy were examined. The expressions of TP, DPD, EGFR, and VEGF protein and TP, DPD, TS and OPRT mRNA were evaluated by using ELISA and qRT-PCR, respectively. Patients were divided into subgroups according to the biomarker expression levels by using a tree-based regression model with baseline patient characteristics as explanatory factors.

Results

Among 2128 patients from the 217 institutions enrolled between Apr. 2009 and Mar. 2012, 2018 were used for analysis. The protein and mRNA expressions were successfully estimated in 100% and 89% of the examined samples, respectively. The logarithmic values of expressions of all examined biomarkers followed normal distributions.

In the tree-based model, "tumor location" was the most relevant variable to explain the expression of TP protein and OPRT mRNA (p < 0.001); TP protein and OPRT mRNA were expressed higher in the right-sided and left-sided colon cancers, respectively. "Histological type" was also relevant to explain the expression of VEGF and DPD protein, and TP, DPD and TS mRNA (p = 0.001); VEGF protein were expressed higher in well to moderately differentiated tumors, while the others were expressed higher in poorly ones. There was no correlation between EGFR protein expression and patient characteristics.

Conclusions

This large cohort study revealed considerable degrees of correlations between tumor location as well as histological type and the intratumoral expression of TP, DPD, TS, OPRT, and VEGF. The results would provide useful information for future studies in personalization of chemotherapy using 5-FU derivatives.

Disclosure

M. Ishiguro: B-CAST study is conducted as a part of joint research of Tokyo Medical and Dental University and the Foundation for Biomedical Research and Innovation (FBRI), with funding from FBRI. All authors declare no relevant competing interest.All other authors have declared no conflicts of interest.