This Article Full Text Full Text (PDF) Purchase Article View Shopping Cart Alert me when this article is cited Alert me if a correction is posted Services Email this article to a colleague Similar articles in this journal Alert me to new issues of the journal Save to my personal folders Download to citation manager Rights & Permissions Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Liersch, T. Articles by Jakob, C. Search for Related Content PubMed Articles by Liersch, T. Articles by Jakob, C. Social Bookmarking                            What's this?

Lymph Node Status and TS Gene Expression Are Prognostic Markers in Stage II/III Rectal Cancer After Neoadjuvant Fluorouracil-Based Chemoradiotherapy

Torsten Liersch, Claus Langer, B. Michael Ghadimi, Bettina Kulle, Daniela E. Aust, Gustavo B. Baretton, Wolfgang Schwabe, Peter Häusler, Heinz Becker, Christiane Jakob

From the Department of General Surgery, University Medical Center, Göttingen; Institute for Pathology, University of Technology, Dresden; Oncoscreen GmbH, Jena, Germany; and the Department of Biostatistics, Institute for Basic Medical Sciences, University of Oslo, Oslo, Norway.

Address reprint requests to Torsten Liersch, MD, Department of General Surgery University Medical Center, Göttingen, Robert-Koch-Str 40, D-37075 Göttingen, Germany; e-mail: tliersc{at}gwdg.de

Purpose According to the CAO/ARO/AIO-94 trial of the German Rectal Cancer Study Group, preoperative combined fluorouracil (FU) -based long-term chemoradiotherapy (CT/RT) is recommended for patients with International Union Against Cancer (UICC) stage II/III rectal cancer. However, despite the local benefit of neoadjuvant treatment, the overall prognostic value remains uncertain in comparison with adjuvant CT/RT. Furthermore, the prognostic value of molecular biomarkers, such as thymidylate synthase (TS), thymidine phosphorylase (TP), and dihydropyrimidine dehydrogenase (DPD), all of which are involved in the FU metabolism, is unknown in neoadjuvant settings. We assessed the impact of standardized preoperative CT/RT and intratumoral TS, TP, and DPD levels on patient outcome.

Patients and Methods Forty patients with rectal cancer pretherapeutic UICC stage II/III, receiving preoperative FU-based CT/RT (CAO/ARO/AIO-94 trial) followed by standardized surgery, including total mesorectal excision, were investigated. Downsizing, downstaging, tumor regression, as well as TS, TP, and DPD gene expression of post-treatment surgical specimens were correlated with disease-free survival (DFS) and overall survival (OS).

Results Significant downsizing (P < .001) and downstaging (P = .001) were achieved with preoperative CT/RT. During a median follow-up of 49 months (95% CI, 43 to 58 months), the cancer recurrence rate was 28.2%. DFS and OS were significantly increased in patients with downstaging (P < .001 and P = .003, respectively), compared with patients without downstaging. All patients who developed cancer recurrence had a persistent positive lymph node status after preoperative CT/RT (P < .001) and a significantly higher TS gene expression (P = .035) compared with those patients without recurrence.

Conclusion Persistent positive lymph node status and high intratumoral TS expression after preoperative CT/RT are predictive of an unfavorable prognosis in rectal cancer UICC stage II/III.

Authors' disclosures of potential conflicts of interest and author contributions are found at the end of this article.

CiteULike    Complore    Connotea    Del.icio.us    Digg    Facebook    Reddit    Technorati    Twitter    What's this?

This article has been cited by other articles:

				C. S.-C. Wong, M.-T. Cheung, B. B.-Y. Ma, E. Pun Hui, A. C.-L. Chan, C.-K. Chan, K.-C. Lee, W. Cheuk, M. Y.-Y. Lam, M. C.-K. Wong, et al. Isolated Tumor Cells and Circulating CK20 mRNA in pN0 Colorectal Cancer Patients International Journal of Surgical Pathology, April 1, 2008; 16(2): 119 - 126. [Abstract] [PDF]

				R. Fietkau and G. Klautke Adjuvant Chemotherapy Following Neoadjuvant Therapy of Rectal Cancer: The Type of Neoadjuvant Therapy (chemoradiotherapy or radiotherapy) May Be Important for Selection of Patients J. Clin. Oncol., January 20, 2008; 26(3): 507 - 508. [Full Text] [PDF]

				B. D. Minsky Adjuvant Management of Rectal Cancer: The More We Learn, the Less We Know J. Clin. Oncol., October 1, 2007; 25(28): 4339 - 4340. [Full Text] [PDF]

				L. Collette, J.-F. Bosset, M. den Dulk, F. Nguyen, L. Mineur, P. Maingon, L. Radosevic-Jelic, M. Pierart, and G. Calais Patients With Curative Resection of cT3-4 Rectal Cancer After Preoperative Radiotherapy or Radiochemotherapy: Does Anybody Benefit From Adjuvant Fluorouracil-Based Chemotherapy? A Trial of the European Organisation for Research and Treatment of Cancer Radiation Oncology Group J. Clin. Oncol., October 1, 2007; 25(28): 4379 - 4386. [Abstract] [Full Text] [PDF]

				W.-S. Wang, P.-M. Chen, T.-J. Chiou, J.-H. Liu, J.-K. Lin, T.-C. Lin, H.-S. Wang, and Y. Su Epidermal Growth Factor Receptor R497K Polymorphism Is a Favorable Prognostic Factor for Patients with Colorectal Carcinoma Clin. Cancer Res., June 15, 2007; 13(12): 3597 - 3604. [Abstract] [Full Text] [PDF]

				P. G. Johnston Prognostic Markers of Local Relapse in Rectal Cancer: Are We Any Further Forward? J. Clin. Oncol., September 1, 2006; 24(25): 4049 - 4050. [Full Text] [PDF]