Thymidylate synthase expression in primary colorectal cancer as a predictive marker for the response to 5-fluorouracil- and oxaliplatin-based preoperative chemotherapy for liver metastases

Hiroshi Takeyama; Tomoko Wakasa; Keisuke Inoue; Kotaro Kitani; Masanori Tsujie; Takafumi Ogawa; Masao Yukawa; Yoshio Ohta; Masatoshi Inoue

doi:10.3892/mco.2018.1623

Thymidylate synthase expression in primary colorectal cancer as a predictive marker for the response to 5-fluorouracil- and oxaliplatin-based preoperative chemotherapy for liver metastases

Mol Clin Oncol. 2018 Jul;9(1):3-10. doi: 10.3892/mco.2018.1623. Epub 2018 May 10.

Authors

Hiroshi Takeyama¹, Tomoko Wakasa², Keisuke Inoue¹, Kotaro Kitani¹, Masanori Tsujie¹, Takafumi Ogawa³, Masao Yukawa¹, Yoshio Ohta², Masatoshi Inoue¹

Affiliations

¹ Department of Gastroenterological Surgery, Kindai University Nara Hospital, Ikoma, Nara 630-0293, Japan.
² Department of Pathology, Kindai University Nara Hospital, Ikoma, Nara 630-0293, Japan.
³ Department of Chemical Science and Engineering, Graduate School of Engineering, Kobe University, Kobe, Hyogo 657-8501, Japan.

Abstract

In patients with colorectal liver metastases (CRLM), predictive markers for response to preoperative chemotherapy are lacking. The aim of the present study was to evaluate the expression of thymidylate synthase (TS) and excision repair cross-complementation group 1 (ERCC1) as predictive markers in CRLM. A total of 24 patients with CRLM were included in this study. Tumor response was evaluated using the tumor regression grade (TRG) and Response Evaluation Criteria in Solid Tumors (RECIST) methods. TS and ERCC1 expression in paired CRLM and primary lesions were assessed by immunohistochemistry. We analyzed correlations between i) the response to preoperative chemotherapy evaluated by TRG and RECIST, ii) TS and ERCC1 expression and the response evaluated by TRG and RESICT, and iii) TS and ERCC1 expression in matched pairs of primary tumor and CRLM. The preoperative chemotherapy response evaluated by TRG and RECIST was significantly associated (P=0.0005). The response based on RECIST criteria and TRG was significantly associated with TS expression in the primary tumor (P=0.0272, and P=0.0137, respectively). No correlations were detected between marker expression in the primary tumor and in CRLM for either TS or ERCC1 (P=0.371 and P=1.00, respectively). Our data suggested that TS expression in the primary tumor is a predictive marker of preoperative chemotherapy response in CRLM based on both TRG and RECIST methods.

Keywords: chemosensitivity; colorectal cancer; colorectal liver metastases; excision repair cross-complementation group 1; preoperative chemotherapy; thymidylate synthase.