Downregulation of TS, DPD, ERCC1, GST-Pi, EGFR, and HER2 gene expression after neoadjuvant three-modality treatment in patients with esophageal cancer

BACKGROUND: To find out if neoadjuvant therapy could alter tumor response determinants that might affect tumor sensitivity to the treatment, we investigated intratumoral expressions of genes associated with chemosensitiviry, radiosensitivity, or both before and after radiochemotherapy. STUDY DESIGN: Twenty-four patients with locally advanced, resectable esophageal cancer (cT2-4,Nx,MO) received neoadjuvant 5-FU/cisplatin/36 Gy treatment followed by transthoracic en bloc esophagectomy. Expression levels of thymidylate synthase, dihyropyrimidine dehydrogenase, excision repair cross-complementing gene 1, glutathione S-transferase Pi, epidermal growth factor receptor, and HER2 were measured in matched preradiochemotherapy endoscopic tumor biopsies and in postradiochemotherapy resection specimens. mRNA was isolated from formalin-fixed, paraffin-embedded, laser microdissected tumor tissues, and a quantitative fluorescen t dye real-time reverse transcription polymerase chain reaction system was used for gene expression measurement. RESULTS: There was a significant reduction in the expression levels of thymidylate synthase (p < 0.01), dihydropyrimicline dehydrogenase (p = 0.03), excision repair cross-complementing gene 1 (p < 0.01), glutathione S-transferase Pi (p = 0.03), HER2 (p < 0.01), and epidermal growth factor receptor (p = 0.04). The change in the levels of epidermal growth factor receptor mRNA Z in post-compared with pretreatment specimens was significantly associated with the histo topathologic grade of regression (p = 0.01). CONCLUSIONS: The expression levels of a set of genes that are possible determinants of 5-FU/cisplatin/ radiation therapy antitumor activity are significantly downregulated by neoadjuvant radiochemotherapy in esophageal cancer. (J Am Coll Sur, 2005;200:336-344. (C) 2005 by the ZD American College of Surgeons)