gms | German Medical Science

27th German Cancer Congress Berlin 2006

German Cancer Society (Frankfurt/M.)

22. - 26.03.2006, Berlin

The thymidylate synthase promoter polymorphism and prognosis in neoadjuvant treated and primarily resected advanced gastric cancer patients

Meeting Abstract

  • corresponding author presenting/speaker Gisela Keller - Institut für Pathologie, TU München, München, Deutschland
  • Katja Ott - Chirurgische Klinik, TU München, Klinikum rechts der Isar, München
  • Noemi Marton - Chirurgische Klinik, TU München, Klinikum rechts der Isar, München
  • Holger Vogelsang - Chirurgische Klinik, TU München, Klinikum rechts der Isar, München
  • Karen Becker - Institut für Pathologie, TU München, München
  • Christoph Schuhmacher - Chirurgische Klinik, TU München, Klinikum rechts der Isar, München
  • Alexander Novotny - Chirurgische Klinik, TU München, Klinikum rechts der Isar, München
  • Florian Lordick - Chirurgische Klinik, TU München, Klinikum rechts der Isar, München
  • Heinz Höfler - Institut für Pathologie, TU München, München
  • Jörg Rüdiger Siewert - Chirurgische Klinik, TU München, Klinikum rechts der Isar, München

27. Deutscher Krebskongress. Berlin, 22.-26.03.2006. Düsseldorf, Köln: German Medical Science; 2006. DocOP601

The electronic version of this article is the complete one and can be found online at: http://www.egms.de/en/meetings/dkk2006/06dkk709.shtml

Published: March 20, 2006

© 2006 Keller et al.
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Outline

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Purpose: We evaluated DNA polymorphisms in the thymidylate synthase (TS) for an association with response and survival in locally advanced gastric cancer treated with primary resection or 5-FU based preoperative chemotherapy (CTx). Recently we found an association with prognosis, but not response in neadjuvant treated gaastric cancer.

Experimental Design: The DNA of 205 patients completely resected patients (102 with CTx; 103 without CTx) was isolated from blood or from nontumorous tissues. Genotyping of the tandem repeat polymorphism in the promoter region of the TS gene was performed by PCR.

Results: 53 (52%) of the patients with primary resection had the 2R/3R genotype, 28 (27%) the 3R/3R and 22 (21%) the 2R/2R genotype. 46 (45%) of the patients with neoadjuvant CTx showed the 2R/3R genotype, 29 (28%) the 3R/3R genotype and 27 (27%) the 2R/2R genotype (p=0.60). In the CTx-group, the TS genotypes were not associated with clinical (p=0.93) or histopathological response (p=0.71), but were significantly related to survival (Median survival in months: 3R/3R: 35,2; 2R/3R: n.e; 2R/2R: n.e.; p=0,003). In contrast there is no survival difference in the primary resected patients regarding the genotype (3R/3R: 33,3; 2R/3R: 47,6; 2R/2R: 32,0; p=0,83). Comparing survival between completely resected patients with and without CTx in the respective TS genotype groups, a significant survival benefit for the patients with CTx was found for the 2rpt/2rpt (n=49; p=0.002) and 2rpt/3rpt genotypes (n=99; p=0.004), but not for the 3rpt/3rpt genotype (n=57; p=0.93).

Conclusion: Our results show that patients` prognosis after CTx was associated with the TS genotype. Patients with the 3rpt/3rpt genotype did not benefit from CTx. Thus a different CTx or primary surgery might be more appropriate for these patients.