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.
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.
Langer
Rupert
R
Institute of Pathology, Klinikum Rechts der Isar, Technische Universität, München, Germany.
Specht
Katja
K
Becker
Karen
K
Ewald
Philipp
P
Ott
Katja
K
Lordick
Florian
F
Siewert
Jörg-Rüdiger
JR
Höfler
Heinz
H
D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1 / Q000235:genetics; D000230:Adenocarcinoma / Q000188:drug therapy* / Q000378:metabolism; D000368:Aged; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D002945:Cisplatin / Q000008:administration & dosage; D004938:Esophageal Neoplasms / Q000188:drug therapy* / Q000378:metabolism; D005260:Female; D005472:Fluorouracil / Q000008:administration & dosage; D006801:Humans; D008297:Male; D008875:Middle Aged; D027425:ATP-Binding Cassette, Sub-Family C Proteins / Q000235:genetics; D020360:Neoadjuvant Therapy; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013940:Thymidylate Synthase / Q000235:genetics
D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1; D002945:Cisplatin; D005472:Fluorouracil; D027425:ATP-Binding Cassette, Sub-Family C Proteins; D013940:Thymidylate Synthase; C421109:multidrug resistance-associated protein 1