Roles of thymidylate synthase and dihydropyrimidine dehydrogenase expression in blood as predictors of response to multimodal therapy in esophageal cancer

• Published in: Surgery Vol. 151; no. 2; pp. 306 - 312
• Main Authors: Brabender, Jan, MD, Metzger, Ralf, MD, Vallböhmer, Daniel, MD, Ling, Frederike, MD, Neiss, Susanne, MTA, Bollschweiler, Elfriede, MD, Schneider, Paul M., MD, Hölscher, Arnulf H., MD, Grimminger, Peter P., MD
• Format: Journal Article
• Language: English
• Published: New York, NY Mosby, Inc 01-02-2012; Elsevier
• Subjects: Adenocarcinoma - blood; Adenocarcinoma - therapy; Adult; Aged; Biological and medical sciences; Biomarkers, Tumor - blood; Carcinoma, Squamous Cell - blood; Carcinoma, Squamous Cell - therapy; Chemoradiotherapy; Combined Modality Therapy; Dihydrouracil Dehydrogenase (NADP) - blood; Dihydrouracil Dehydrogenase (NADP) - genetics; Esophageal Neoplasms - blood; Esophageal Neoplasms - therapy; Esophagus; Female; Gastroenterology. Liver. Pancreas. Abdomen; General aspects; Humans; Male; Medical sciences; Middle Aged; Neoadjuvant Therapy; Predictive Value of Tests; RNA - blood; Sensitivity and Specificity; Surgery; Thymidylate Synthase - blood; Thymidylate Synthase - genetics; Treatment Outcome; Tumors; Enzyme; Transferases; Esophageal disease; ); Malignant tumor; Dihydropyrimidine dehydrogenase (NADP; Thymidylate synthase; Esophagus cancer; Blood; Medicine; Treatment; Methyltransferases; Surgery; Digestive diseases; Oxidoreductases; Predictive factor; Cancer
• ISSN: 0039-6060; 1532-7361
• DOI: 10.1016/j.surg.2011.07.018

Background Thymidylate synthetase (TS) and dihydropyrimidine dehydrogenase (DPD) RNA expression in peripheral blood was examined as a noninvasive molecular predictor of response to neoadjuvant radiochemotherapy in patients with locally advanced cancer of the esophagus. Methods Blood samples were drawn from 29 patients with esophageal cancer (10 squamous cell carcinomas and 19 adenocarciomas) before neoadjuvant radiochemotherapy. After extraction of cellular tumor RNA from blood samples, quantitative expression analysis of TS and DPD was performed with quantitative real-time reverse-transcription polymerase chain reaction. Results Twenty of 29 (68%) of patients had a minor histopathologic response, and 9 of 29 (32%) had a major response to neadjuvant radiochemotherapy. RNA expression in the blood of patients was detectable for TS in 86%, for DPD in 97%, and in 100% for β-actin. No significant associations were detected between TS and DPD expression levels and clinical variables of the patients. A high expression level for TS was associated with a minor response to neoadjuvant treatment ( P = .046), while there was no significant association between DPD and response to therapy. Combined analysis of TS and DPD expression increased the specificity for the prediction of response to 100%. No major responder to therapy had high expression levels for both genes in their peripheral blood. Conclusion Quantitation of TS and DPD in peripheral blood may be a highly specific analysis to identify a subset of patients who do not respond to neoadjuvant radiochemotherapy and may therefore prevent expensive, noneffective, and potentially harmful therapies in a substantial number of patients with esophageal cancer.