Free circulating mRNA in plasma from breast cancer patients and clinical outcome.
ABSTRACT We studied by real-time PCR cyclin D1 and thymidylate synthase (TS) mRNA in plasma as possible markers of clinical outcome in breast cancer. We observed poor outcome in patients with presence of cyclin D1 mRNA in good-prognosis groups, such as negative vascular invasion. Presence of both markers was associated with non-response to treatment after relapse. In patients treated with tamoxifen, a trend to significant relation between poor outcome and cyclin D1 mRNA was found. Cyclin D1 mRNA in plasma could identify patients with poor overall survival in good-prognosis groups and patients non-responsive to tamoxifen.
- Genes Chromosomes and Cancer 01/2003; 35(4):375-6. · 3.55 Impact Factor
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ABSTRACT: 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. 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. 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. 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.Clinical Cancer Research 05/2006; 12(7 Pt 1):2095-100. · 7.84 Impact Factor
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ABSTRACT: Thymidylate synthase (TS), Dihydropyrimidine dehydrogenase (DPD) and Thymidine Phosphorylase (TP) gene expressions are reported to be predictive markers for 5-fluorouracil (5-FU) sensitivity in gastrointestinal cancer. However, in breast cancer, it is still controversial whether those molecular markers predict 5-FU sensitivity or not. One possible reason for the difficulty may be the histological heterogeneity in breast cancer specimens. In this study, TS, DPD and TP mRNA expression in 40 breast cancer tumors were semi-quantified separately in cancer cells (Ca), cancerous stroma (Str) and normal glands (Nor) using laser capture microdissection and real time RT-PCR (LCM+RT-PCR). The histoculture drug response assay (HDRA) for 5-FU sensitivity was performed for 22 tumors. TS and TP mRNA expressions were higher in Ca than Str, although DPD gene expression was lower in Ca than Str. The group of high TS and high DPD gene expression in Ca was resistant to 5-FU, and the group of low TS and low DPD gene expression in Ca was sensitive to 5-FU (P=0.048 chi-square test). TS and DPD mRNA expressions measured using LCM+RT-PCR might be useful predictive markers for 5-FU sensitivity in human breast cancer.Cancer Letters 07/2005; 223(1):103-11. · 4.26 Impact Factor