Predictive markers of the efficacy of colon adenocarcinoma treatment by 5-fluoropyrimidines determined by means of immunohistochemistry method

Abstract


5-fluorouracil (5-FU) has remained the treatment of choice in the adjuvant and palliative setting of colon cancer (CC).The purpose of this study was to evaluate the expression of the thymidine phosphorylase (TP), thymidylate synthase (TS) and dihydropyrimidine dehydrogenase (DPYD)in CC patients treated with 5-fluorouracil (5-FU) to determine their predictive and prognostic significance. Immunohistochemistry (IHC) analysis of the expression of proteins was performed on tumour tissue of 104 patients with stage IV colon cancer. All patient was treated withfluoropyrimidine/antifolate-based therapy (FOLFOX, De Gramont, FOLFIRI). Usedmultivariate logistic regression analyses we found the level of expression of proteins thymidine phosphorylase (TP), thymidylate synthase (TS) as predictors efficiency 5 - fluoropyrimidine with adenocarcinoma of the colon. The value of expression of TP and TS has a statistically significant effect (p = 0,006 and p = 0.0036) on time to disease progression, respectively.Our data demonstrated the efficacy of the 5-fluoropyrimidine chemotherapy colon adenocarcinoma may be utilized evaluation of expression of TS and TP.

Grigoriy Aleksandrovich Raskin

Russian Research Centre for Radiology and Surgical Technologies

Email: rasking@list.ru
MD, PhD, chief researcher

Rashida Vakhidovna Orlova

Saint Petersburg State University

M.D., PhD, Dsc, professor, Head of Oncology department

Anna Eduardovna Protasova

Saint Petersburg State University

M.D., PhD, Dsc, professor of Oncology department

Sergey Aleksandrovich Koshkin

Saint Petersburg State University

resident of Oncology, Medical Faculty

Ruslan Ivanovich Glushakov

Kirov Military Medical Academy

Email: glushakovruslan@gmail.com
Ph.D., senior assistant chief of the division of scientific investigation

  1. Kwon H. C., Roh M. S., Oh S. Y. et al. Prognostic value of expression of ERCC1, thymidylate synthase, and glutathione S-transferase P1 for 5-fluorouracil/oxaliplatin chemotherapy in advanced gastric cancer // Annals of Oncology. - 2007. - Vol. 18 (3). - P. 504-509.
  2. Uchida P. V., Danenberg K. D., Danenberg J. L. Grem Thymidylate synthase, dihydropyrimidine dehydrogenase, ERCC1, and thymidine phosphorylase gene expression in primary and metastatic gastrointestinal adenocarcinoma tissue in patients treated on a phase I trial of Oxaliplatin and capecitabine // BMC Cancer. - 2008. - Vol. 23. - P. 1121-1130.
  3. Zucali P. A., Giovannetti E., Destro A. et al. Thymidylate synthase and excision repair cross-complementing group-1 as predictors of responsiveness in mesothelioma patients treated with pemetrexed/carboplatin // Clin. Cancer Res. - 2011. - Vol. 17 (8). - P. 2581-2590.
  4. Karlberg M., Ohrling K., Edler D. et al. Prognostic and predictive value of thymidylate synthase expression in primary colorectal cancer // Anticancer Res. - 2010. - Vol.30 (2). - P. 645-651.
  5. Ishibashi K., Okada N., Ishiguro T. et al. The expression of thymidylate synthase (TS) and excision repair complementing-1 (ERCC-1) protein in patients with unresectable colorectal cancer treated with mFOLFOX6 therapy // Gan To Kagaku Ryoho. - 2010. - Vol. 37 (12). - P. 2532-2535.
  6. Schneider H. B., Becker H. Impact of dihydropyrimidine dehydrogenase on 5-fluorouracil treatment in cancer patients // Eur. J. Med. Res. - 2004. - Vol. 8. - P.226-228.
  7. Honda J., Sasa M., Moriya T. et al. Thymidine phosphorylase and dihydropyrimidine dehydrogenase are predictive factors of therapeutic efficacy of capecitabine monotherapy for breast cancer - preliminary result // J. Med. Investigations. - 2008. - Vol. 55. - P. 54-60.

Views

Abstract - 284

PDF (Russian) - 232

PlumX


Copyright (c) 2014 Raskin G.A., Orlova R.V., Protasova A.E., Koshkin S.A., Glushakov R.I.

Creative Commons License
This work is licensed under a Creative Commons Attribution 4.0 International License.