This Article Full Text Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted Services Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Langer, R. Articles by Höfler, H. Search for Related Content PubMed PubMed Citation Articles by Langer, R. Articles by Höfler, H.

Association of Pretherapeutic Expression of Chemotherapy-Related Genes with Response to Neoadjuvant Chemotherapy in Barrett Carcinoma

Authors' Affiliations: ¹ Institutes of Pathology and ² Medical Statistics and Epidemiology and ³ Department of Surgery, Klinikum Rechts der Isar, Technische Universität München, Munich, Germany and ⁴ Institutes of Pathology, GSF National Research Center for Environment and Health, Neuherberg, Germany

Requests for reprints: Heinz Hoefler, Institute of Pathology, Klinikum Rechts der Isar, Technische Universität München Trogerstrasse 18, D-81675 München, Germany. Phone: 49-89-414-04160; Fax: 49-89-414-04865; E-mail: Hoefler{at}lrz.tu-muenchen.de.

Purpose: We analyzed pretherapeutic gene expression patterns of patients with locally advanced adenocarcinomas of the esophagus with regard to response to neoadjuvant chemotherapy.

Experimental Design: Pretherapeutic, paraffin-embedded, formalin-fixed endoscopic esophageal tumor biopsies of 38 patients with locally advanced esophageal adenocarcinomas (Barrett adenocarcinoma) were included. All patients underwent two cycles of cisplatin and 5-fluorouracil (5-FU) therapy with or without additional paclitaxel followed by abdominothoracal esophagectomy. RNA expression levels of 5-FU metabolism-associated genes thymidylate synthase, thymidine phosphorylase, dihydropyrimidine dehydrogenase, methylenetetrahydrofolate reductase, MAP7, and ELF3, of platinum- and taxane-related genes caldesmon, ERCC1, ERCC4, HER-2/neu, and GADD45, and of multidrug resistance gene MRP1 were determined using real-time reverse transcriptase-PCR. Expression levels were correlated with response to chemotherapy, histopathologically assessed in surgically resected specimens.

Results: Responding patients showed significantly higher pretherapeutic expression levels of MTHFR (P = 0.012), caldesmon (P = 0.016), and MRP1 (P = 0.007). In addition, patients with high pretherapeutic MTHFR and MRP1 levels had a survival benefit after surgery (P = 0.013 and P = 0.015, respectively). Additionally, investigation of intratumoral heterogeneity of gene expression of relevant genes (MTHFR, caldesmon, HER-2/neu, ERCC4, and MRP1), verified in nine untreated Barrett adenocarcinomas by examination of five distinct tumor areas, revealed no significant heterogeneity in gene expression indicating that expression profiles obtained from biopsy material may yield a representative genetic expression profile of total tumor tissue.

Conclusions: Our results indicate that determination of mRNA levels of few genes may be useful for the prediction of the success of neoadjuvant chemotherapy in individual cancer patients with locally advanced Barrett adenocarcinoma.

This article has been cited by other articles:

				D. Breen and F. Barlesi The place of excision repair cross complementation 1 (ERCC1) in surgically treated non-small cell lung cancer Eur. J. Cardiothorac. Surg., May 1, 2008; 33(5): 805 - 811. [Abstract] [Full Text] [PDF]

				C. Duong, D. M. Greenawalt, A. Kowalczyk, M. L. Ciavarella, G. Raskutti, W. K. Murray, W. A. Phillips, and R. J. S. Thomas Pretreatment Gene Expression Profiles Can Be Used to Predict Response to Neoadjuvant Chemoradiotherapy in Esophageal Cancer. Ann. Surg. Oncol., December 1, 2007; 14(12): 3602 - 3609. [Abstract] [Full Text] [PDF]

				A. Handra-Luca, J. Hernandez, G. Mountzios, E. Taranchon, J. Lacau-St-Guily, J.-C. Soria, and P. Fouret Excision Repair Cross Complementation Group 1 Immunohistochemical Expression Predicts Objective Response and Cancer-Specific Survival in Patients Treated by Cisplatin-Based Induction Chemotherapy for Locally Advanced Head and Neck Squamous Cell Carcinoma Clin. Cancer Res., July 1, 2007; 13(13): 3855 - 3859. [Abstract] [Full Text] [PDF]

				K. Ott, W. A. Weber, F. Lordick, K. Becker, R. Busch, K. Herrmann, H. Wieder, U. Fink, M. Schwaiger, and J.-R. Siewert Metabolic Imaging Predicts Response, Survival, and Recurrence in Adenocarcinomas of the Esophagogastric Junction J. Clin. Oncol., October 10, 2006; 24(29): 4692 - 4698. [Abstract] [Full Text] [PDF]

				K. A. Olaussen, A. Dunant, P. Fouret, E. Brambilla, F. Andre, V. Haddad, E. Taranchon, M. Filipits, R. Pirker, H. H. Popper, et al. DNA repair by ERCC1 in non-small-cell lung cancer and cisplatin-based adjuvant chemotherapy. N. Engl. J. Med., September 7, 2006; 355(10): 983 - 991. [Abstract] [Full Text] [PDF]