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 Xi, H. Articles by Schneider, P. M. Search for Related Content PubMed PubMed Citation Articles by Xi, H. Articles by Schneider, P. M.

High Cyclooxygenase-2 Expression Following Neoadjuvant Radiochemotherapy Is Associated with Minor Histopathologic Response and Poor Prognosis in Esophageal Cancer

Authors' Affiliations: Departments of ¹ Visceral and Vascular Surgery and ² Radiation Oncology and ³ Institute of Pathology, University of Cologne, Cologne, Germany and ⁴ Department of General Surgery, Beijing Hospital, Beijing, People's Republic of China

Requests for reprints: Paul M. Schneider, Department of Visceral and Vascular Surgery, University of Cologne, Joseph-Stelzmann-Strasse 9, 50931 Cologne, Germany. Phone: 49-221-478-4829; Fax: 49-221-478-6258; E-mail: paul.schneider{at}uk-koeln.de.

Purpose: High expression of cyclooxygenase-2 (COX-2) was shown to inhibit chemotherapy- and radiotherapy-induced apoptosis. We analyzed the association of COX-2 mRNA and protein expression with histomorphologic response to neoadjuvant radiochemotherapy in esophageal cancer.

Experimental Design: Fifty-two patients with resectable esophageal cancers (cT2-4, N_x, and M₀) received neoadjuvant radiochemotherapy (cisplatin, 5-5-fluorouracil, 36 Gy) followed by transthoracic en bloc esophagectomy. Histomorphologic regression was defined as major response when resected specimens contained less than 10% of residual vital tumor cells. RNA was isolated from endoscopic biopsies (paired tumor and normal tissue) before neoadjuvant treatment and quantitative real-time reverse transcriptase-PCR (Taqman) assays were done to determine COX-2 mRNA expression levels standardized for ß-actin. COX-2 protein expression in pretreatment biopsies and post-therapeutic resection specimens was analyzed by immunostaining of tumor cells.

Results: Median COX-2 mRNA expression levels were significantly (P < 0.0001) different between paired tumor (median, 2.2) and normal tissues (median, 0.159). Comparison of pre-therapeutic and posttherapeutic specimens showed a significant difference (P < 0.006) in COX-2 protein expression. Twelve of 52 tumors showed down-regulation and 3 of 52 showed up-regulation of COX-2 protein expression during neoadjuvant radiochemotherapy. High COX-2 protein expression in post-therapeutic resection specimens was significantly associated with minor histopathologic response (P < 0.04) and poor prognosis (5-year survival probabilities: 26.3 ± 8.2% for minor and 58.6% ± 12.9% for major histopathologic response; P < 0.01).

Conclusion: High COX-2 protein expression following neoadjuvant radiochemotherapy in resection specimens is significantly associated with minor histopathologic response to neoadjuvant therapy and very poor prognosis.

This article has been cited by other articles:

				P. de Heer, M. J.E.M. Gosens, E. C. de Bruin, N. G. Dekker-Ensink, H. Putter, C. A.M. Marijnen, A. J.C. van den Brule, J. H. J.M. van Krieken, H. J.T. Rutten, P. J.K. Kuppen, et al. Cyclooxygenase 2 Expression in Rectal Cancer Is of Prognostic Significance in Patients Receiving Preoperative Radiotherapy Clin. Cancer Res., May 15, 2007; 13(10): 2955 - 2960. [Abstract] [Full Text] [PDF]