Die Bedeutung der Thymidinphosphorylase bei Patienten mit lokal fortgeschrittenem Rektumkarzinom (UICC-Stadium-II/-III) im Kontext einer 5-FU basierten multimodalen Therapie

The significance thymidine phosphorylase has on patients with locally advanced rectal cancer (UICC-Stadium-II/-III) with regard to a 5-FU based multimodal therapy

von Matthias Specking
Dissertation
Datum der mündl. Prüfung:2014-06-23
Erschienen:2014-06-19
Betreuer:PD Dr. Torsten Liersch
Gutachter:PD Dr. Torsten Liersch
Gutachter:Prof. Dr. Peter Burfeind
Zum Verlinken/Zitieren: http://dx.doi.org/10.53846/goediss-4536

 

 

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Englisch

Thymidine phosphorylase (TP) is an enzyme, which is involved in the physiological metabolism of each cell. There it acts as an angiogenic factor, but further catalyzes at least three known reactions, which are related to the 5-Fluorouracil (5-FU) metabolism. Previous studies revealed that carcinoma cells, compared with normal tissue, contain an increased expression of TP. For this reason, the present study, immunohistochemically examined the tissue of 223 patients with locally advanced rectal cancer for expression of TP. All patients were subject to multimodal therapy regimens under standardized conditions. These were based on randomized, multicenter Phase-II/-III studies. The studied patient population included 186 biopsies and 223 rectum resectates. Initially, data of clinicopathological parameters and the follow-up period was collected. Subsequently, patients were divided into three treatment groups; Group A (n = 41) was primarily operated, group B (n = 69) received neoadjuvant RT / CTx with 5-FU, and Group C (n = 113) was administered neoadjuvant RT / CTx with 5-FU plus Oxaliplatin. Later, all patients were additionally introduced to the appropriate adjuvant chemotherapy, with regard to their particular regimen. The results of the analysis of the pre-treatment biopsies showed that primarily operated patients with an increased TP expression in the examined tissue, developed local recurrences (p = 0.001) significantly more often. Moreover, the analysis showed that pre-therapeutic biopsies (Group C) with a high TP expression developed significantly fewer distant metastases, than patients with low TP expression (p = 0.035). However, there was neither a significant correlation for the reported results related to the resected specimens, nor for disease-specific overall survival. As a result of this study, TP demonstrates to be of limited suitability as a molecular laboratory parameter for treatment stratification. For pretreatment biopsies, a high TP expression was scarcely observed, since this tissue mostly came from more peripheral tumor areas. A combination with other biomarkers could make the use of TP as a predictive and prognostic marker in clinical practice more likely.
Keywords: Thymidine phosphorylase; 5-Fluorouracil; rectal cancer
Schlagwörter: Thymidinphosphorylase; Rektumkarzinom; 5-Fluorouracil
 
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