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Cell, Molecular, and Tumor Biology: Cancer Genetics/Gene Expression

Messenger RNA expression of TS and ERCC1 in primary colorectal cancer and corresponding liver metastasis.

University of Southern California, Los Angeles, CA; Tokyo Medical and Dental University, Tokyo, Japan; Response Genetics Inc, Los Angeles, CA

Abstract

B119

Purpose 5-fluorouracil (5-FU) and oxaliplatin play an important role in chemotherapy for patients with colorectal cancer. The expressions of thymidylate synthase (TS) and excision repair cross-complementing factor 1 (ERCC1) have been reported to be prognostic markers for patients with 5-FU/oxaliplatin chemotherapy. The aim of this study was to clarify the association between messenger RNA (mRNA) levels of TS and ERCC1 in primary colorectal cancer and those in corresponding liver metastasis. Methods Formalin-fixed paraffin-embedded tumor specimens of 31 patients with resection for both colorectal cancer and liver metastasis were dissected by laser capture microdissection. After RNA extraction, TS and ERCC1 mRNA levels in both primary tumor and corresponding liver metastasis were measured by real-time reverse transcription-polymerase chain reaction. Results Both TS and ERCC1 mRNA levels in primary tumors were significantly associated with those in synchronous liver metastases (TS, rs = 0.875, p = 0.0024; ERCC1, rs = 0.835, p = 0.0038). TS mRNA levels in primary tumors were also associated with those in metachronous liver metastases (rs = 0.659, p = 0.0065), but not in ERCC1 (rs = 0.319, p = 0.19). In both genes, mRNA levels in metachronous liver metastases were higher than those in primary tumors (TS, p = 0.0084; ERCC1, p = 0.037). However, there were no differences in the TS and ERCC1 mRNA levels between primary tumors and synchronous liver metastasis. Conclusion The measurement of TS and ERCC1 m RNA levels in primary colorectal cancer can predict those in synchronous liver metastases, but not in metachronous ones.