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Thymidylate Synthase Messenger RNA Expression in Plasma from Patients with Colon Cancer: Prognostic Potential

Authors' Affiliations: Deparments of ¹ Medical Oncology and ² Surgery, Hospital Universitario Puerta de Hierro, Madrid and ³ Department of Pathology, Hospital Virgen de la Salud, Toledo, Spain

Requests for reprints: Félix Bonilla, Department of Medical Oncology, Hospital Universitario Puerta de Hierro, C/ San Martín de Porres, 4, E-28035 Madrid, Spain. Phone: 34-91-386-6527; Fax: 34-91-373-7667; E-mail: felixbv{at}stnet.es.

Purpose: Thymidylate synthase (TS), a critical target in fluorouracil-based chemotherapy, is a prognostic marker in colon carcinomas and a predictor of response to treatment. Tumor RNA has been detected in plasma from cancer patients and is associated with poor prognosis. This is the first study to examine extracellular TS mRNA in plasma from patients with colon carcinoma, and its possible relation with TS promoter enhancer region (TSER) polymorphism.

Experimental Design: TS expression was measured in plasma from 88 patients and 26 controls, and in a tumor subgroup of this series by quantitative PCR. Genotyping for TSER polymorphism was done in 60 patients. Clinicopathologic variables were correlated with these molecular changes.

Results: TS mRNA was detected in plasma in 47% of patients, showing significant differences from healthy controls. Patients with TS mRNA in plasma had higher levels of TS in tumor tissue than patients without. The presence of TS mRNA was associated with lymph node metastases and more advanced stages. Polymorphism TSER 3/3 was found in 38% of cases, and was significantly correlated with high amounts of TS mRNA in plasma.

Conclusions: Our results suggest that TS mRNA in plasma originated from tumors, it may indicate poor prognosis and might help to classify tumors in Dukes' stages B and C. The TSER genotype may influence TS mRNA expression in plasma.

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