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Nuclear thymidylate synthase expression in sporadic colorectal cancer depends on the site of the tumor

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Abstract

Colorectal carcinoma (CRC) is a heterogeneous disease with specific epidemiological, pathological, molecular, and clinical characteristics that depend on the location of the tumor relative to the splenic flexure. Thymidylate synthase (TS) is a major target of 5-fluorouracil-based chemotherapy for CRC and high expression of this enzyme in tumor cells can influence the effect of therapy. We examined differences in TS protein expression in nuclei of tumor cells between CRCs located proximal and distal to the splenic flexure. Nuclear TS was detected by immunohistochemistry with a TS 106 monoclonal antibody on tissue microarrays constructed from 269 CRCs. The median histological score of nuclear TS expression of all proximal tumors was two times higher (p = 0.0003) and in men three times higher (p = 0.00023) than that found in distal tumors. In multivariate analysis which included age, sex, Astler–Coller stage, histological grade, and site, only proximal location of the tumor was identified as an independent factor associated with higher TS expression (odds ratio 2.46, 95% confidence interval = 1.29–4.70, p = 0.0062). These results demonstrate significant differences in nuclear TS expression between proximal and distal cancers and suggest the potential importance of the site of the tumor for proper stratification of patients for chemotherapy.

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Acknowledgement

This study was supported by a grant (KBN 2P05B 174 28) from the Polish Committee for Scientific Research.

Disclosure/conflict of interest

All authors declare that they have no conflict of interest to disclose.

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Authors and Affiliations

  1. Department of Oncological Surgery, Pomeranian Medical University, Szczecin, Poland

    Violetta Sulzyc-Bielicka & Jozef Kladny

  2. Department of Genetics and Pathology, Pomeranian Medical University, Szczecin, Poland

    Pawel Domagala

  3. Department of Pathology, Pomeranian Medical University, ul. Unii Lubelskiej 1, 71-252, Szczecin, Poland

    Ewa Majdanik, Maria Chosia & Wenancjusz Domagala

  4. Department of Gastroenterology and Internal Medicine, Pomeranian Medical University, Szczecin, Poland

    Dariusz Bielicki

  5. Department of Laboratory Diagnostics and Molecular Medicine, Pomeranian Medical University, Szczecin, Poland

    Mariusz Kaczmarczyk

  6. Department of Biochemistry and Medical Chemistry, Pomeranian Medical University, Szczecin, Poland

    Krzysztof Safranow

Authors
  1. Violetta Sulzyc-Bielicka
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  2. Pawel Domagala
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  9. Wenancjusz Domagala
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Correspondence to Wenancjusz Domagala.

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Sulzyc-Bielicka, V., Domagala, P., Majdanik, E. et al. Nuclear thymidylate synthase expression in sporadic colorectal cancer depends on the site of the tumor. Virchows Arch 454, 695–702 (2009). https://doi.org/10.1007/s00428-009-0787-x

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  • DOI: https://doi.org/10.1007/s00428-009-0787-x

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