Originally published as JCO Early Release 10.1200/JCO.2005.12.130 on July 11 2005

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Detection of Thymidylate Synthase Expression in Lymph Node Metastases of Colorectal Cancer Can Improve the Prognostic Information

From the Department of Oncology at Radiumhemmet and Department of Surgery, Karolinska University Hospital, Stockholm, Sweden

Address reprint requests to Katarina Öhrling, MD, Department of Oncology at Radiumhemmet, Karolinska University Hospital, S-171 76 Stockholm, Sweden; e-mail: katarina.ohrling{at}karolinska.se

PURPOSE: The level of thymidylate synthase (TS) in primary colorectal cancer (CRC) has been reported as a prognostic marker. The purpose of this study was to determine whether TS expression in lymph node metastases of Dukes' C CRC is a prognostic marker.

PATIENTS AND METHODS: TS expression in the primary tumor and lymph node metastases from 348 patients with Dukes' C CRC was retrospectively assessed using immunohistochemistry and the monoclonal antibody TS 106. The patients had all been enrolled onto our previous study of 862 CRC patients who were included in Nordic trials that randomly assigned the patients to either surgery alone or surgery plus adjuvant chemotherapy.

RESULTS: TS expression in lymph node metastases was a distinct prognostic marker in the entire study group for overall survival (OS; P = .02) and disease-free survival (DFS; P = .04). A low TS expression in the lymph node metastases correlated with a better clinical outcome. In the subgroup of patients treated with surgery alone, the expression of TS in lymph node metastases also had a prognostic value for OS (P = .04) and DFS (P = .03), but this was not the case for the other subgroup who received adjuvant fluorouracil-based chemotherapy (OS, P = .5; DFS, P = .2). The expression of TS in the primary tumor only had a significant prognostic value among patients who were treated with surgery alone (OS, P = .03; DFS, P = .03) and not among the entire patient population.

CONCLUSION: These data show that TS expression in lymph node metastases is a prognostic marker for patients with Dukes' C CRC.

Supported by grants from the King Gustaf V:s Jubilee Foundation, the Cancerföreningen, Stockholm, the Swedish Cancer Society, the Bengt Ihre Foundation of the Swedish Society of Medicine, and the Ruth and Rickard Juhlin Foundation.

Authors' disclosures of potential conflicts of interest are found at the end of this article.

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