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128. Kongress der Deutschen Gesellschaft für Chirurgie

Deutsche Gesellschaft für Chirurgie

03.05. - 06.05.2011, München

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Prognostic Biomarker in rectal cancer patients: Thymidylate Synthase for risk stratification after 5-FU-based neoadjuvant radiochemotherapy

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  • Lena-Christin Conradi - Universitätsmedizin Göttingen, Klinik für Allgemein- und Viszeralchirurgie, Göttingen
  • Annalen Bleckmann - Universitätsmedizin Göttingen, Hämatologie/Onkologie, Göttingen
  • Markus Schirmer - Universitätsmedizin Göttingen, Klinische Pharmakologie, Göttingen
  • Thilo Sprenger - Universitätsmedizin Göttingen, Klinik für Allgemein- und Viszeralchirurgie, Göttingen
  • Peter Jo - Universitätsmedizin Göttingen, Klinik für Allgemein- und Viszeralchirurgie, Göttingen
  • Kia Homayounfar - Universitätsmedizin Göttingen, Klinik für Allgemein- und Viszeralchirurgie, Göttingen
  • Hendrik A. Wolff - Universitätsmedizin Göttingen, Strahlentherapie und Radioonkologie, Göttingen
  • Hilka Rothe - Universitätsmedizin Göttingen, Pathologie, Göttingen
  • Heinz Becker - Universitätsmedizin Göttingen, Klinik für Allgemein- und Viszeralchirurgie, Göttingen
  • Michael Ghadimi - Universitätsmedizin Göttingen, Klinik für Allgemein- und Viszeralchirurgie, Göttingen
  • Tim Beissbarth - Universitätsmedizin Göttingen, Medizinische Statistik, Göttingen
  • Torsten Liersch - Universitätsmedizin Göttingen, Klinik für Allgemein- und Viszeralchirurgie, Göttingen

Deutsche Gesellschaft für Chirurgie. 128. Kongress der Deutschen Gesellschaft für Chirurgie. München, 03.-06.05.2011. Düsseldorf: German Medical Science GMS Publishing House; 2011. Doc11dgch347

doi: 10.3205/11dgch347, urn:nbn:de:0183-11dgch3471

Published: May 20, 2011

© 2011 Conradi et al.
This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by-nc-nd/3.0/deed.en). You are free: to Share – to copy, distribute and transmit the work, provided the original author and source are credited.

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Introduction: Fluorouracil (5-FU) remains the backbone of neoadjuvant radiochemotherapy (RCT) as well as adjuvant therapeutic strategies in multimodal treatment of rectal cancer patients. Due to its central role as the major target of 5-FU thymidylate synthase (TS) is a promising biomarker in rectal cancer. We assessed TS in 208 patients with regard to its predictive/prognostic capacity for disease free (DFS) and overall cancer specific survival (CSS).

Materials and methods: 167 patients with cUICC stages II (28%) and III (72%) received preoperative 5-FU-based RCT followed by total mesorectal excision (TME). A comparison group (n=41) received postoperative RCT after primary TME. All patients were treated after standardized protocols within phase-II/-III-trials of the German Rectal Cancer Study Group. TS levels from pre-treatment biopsies and corresponding resection specimens were assessed by immunohistochemical staining for their impact on DFS and CSS. Additionally, a TS gene polymorphism 28 bp repeat was analysed in respect to intracellular protein expression levels and prognostic significance.

Results: Patients with low TS expression in pre-treatment biopsies showed a correlation with impaired CSS (p=0.015). After neoadjuvant RCT there was evidence of lymph node metastases (ypUICC stage III) in 32.6%. Complete histopathologically confirmed tumor regression (TRG 4) was achieved in 16 patients (9.5%). During follow-up (median 57 months) patients with low intratumoral TS expression and positive nodal status were at high risk for local and/or distant metastatic recurrence (p=0.040). Analysis of the 28bp repeat revealed a correlation of *3/*3 genotype with high TS expression in pretherapeutical biopsies (p=0.059).

Conclusion: TS represents a prognostic biomarker in locally advanced rectal cancer indicating an unfavourable outcome for patients with low TS expression and might help to adapt adjuvant therapy regimens by stratifying patients according to their risk for cancer recurrence.