Comparison of Pretherapeutic and Posttherapeutic Expression Levels of Chemotherapy-Associated Genes in Adenocarcinomas of the Esophagus Treated by 5-Fluorouracil– and Cisplatin-Based Neoadjuvant Chemotherapy

Abstract

We analyzed expression of genes associated with metabolism of chemotherapeutic drugs in locally advanced esophageal adenocarcinomas before and after neoadjuvant chemotherapy to study whether there is a change in gene expression induced by chemotherapy and whether such changes are associated with tumor response or nonresponse. We included 21 patients with locally advanced esophageal adenocarcinomas treated by cisplatin- and 5-fluorouracil (5-FU)-based neoadjuvant chemotherapy before surgery. Messenger RNA was extracted from formalin-fixed, paraffin-embedded preoperative endoscopic esophageal tumor biopsy specimens and tumor tissue specimens after surgical resection. Expression levels of chemotherapy metabolism-associated genes thymidylate synthase (TYMS), thymidine phosphorylase (TP), dihydropyrimidine dehydrogenase (DPD), methylenetetrahydrofolate reductase (MTHFR), multidrug resistance-associated protein 1 (MRP1), and multidrug-resistance gene 1 (MDR1) were determined by quantitative real-time reverse transcriptase-polymerase chain reaction. There was a significant posttherapeutic reduction in the expression levels of TP (P = .028) and MRP1 (P = .006). Furthermore, down-regulation of MRP1 (P = .041) and TYMS (P = .028) after chemotherapy was associated with tumor response to chemotherapy, assessed clinically and by histopathologic tumor regression. Down-regulation of chemotherapy metabolism-associated genes occurs after neoadjuvant chemotherapy and may modulate tumor response to chemotherapy.