Clinical Research Papers:
Overexpression of thymidylate synthase (TYMS) is associated with aggressive tumor features and early PSA recurrence in prostate cancer
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Christoph Burdelski1,*, Christian Strauss2,*, Maria Christina Tsourlakis2, Martina Kluth2, Claudia Hube-Magg2, Nathaniel Melling1, Patrick Lebok2, Sarah Minner2, Christina Koop2, Markus Graefen3, Hans Heinzer3, Corinna Wittmer2, Till Krech2, Guido Sauter2, Waldemar Wilczak2, Ronald Simon2, Thorsten Schlomm3,4, Stefan Steurer2
1General, Visceral and Thoracic Surgery Department and Clinic, University Medical Center Hamburg-Eppendorf, Germany
2Institute of Pathology, University Medical Center Hamburg-Eppendorf, Germany
3Martini-Clinic, Prostate Cancer Center, University Medical Center Hamburg-Eppendorf, Germany
4Department of Urology, Section for translational Prostate Cancer Research, University Medical Center Hamburg-Eppendorf, Germany
*These authors have contributed equally to this work
Ronald Simon, e-mail: email@example.com
Keywords: TYMS, prostate cancer, TMPRSS2-ERG fusion, tissue microarray, prognosis
Received: December 18, 2014 Accepted: January 08, 2015 Published: February 25, 2015
Thymidylate synthase (TYMS) plays a role in DNA synthesis and is a target for 5-fluorouracil. In this study TYMS was analyzed by immunohistochemistry on a tissue microarray containing 11,152 prostate cancers. TYMS expression was higher in neoplastic than in normal prostate epithelium and was detectable in 72.9% of 10,223 interpretable cancers. It was considered strong in 21.9%, moderate in 33.4% and weak in 17.6% of tumors. TYMS overexpression was associated with deletions at 5q21 (p < 0.0001), 6q15 (p < 0.0001) and 3p13 (p = 0.0083) and gradually increased with the total number of these deletions present in the respective cancer sample (p < 0.0001). TYMS expression was unrelated to PTEN deletions (p = 0.9535) but tightly linked to high Gleason grade, advanced pathological tumor stage and early PSA recurrence (p < 0.0001). The prognostic value of TYMS was independent from the ERG status and deletions at 3p13, 5q21, and 6q15. In multivariate analyses the prognostic role of TYMS expression was independent of Gleason grade, pT stage, preoperative PSA, pN stage, or resection margins. TYMS expression analysis might result in clinically useful information in prostate cancer. The striking link to some but not all chromosomal aberrations might suggest a mechanistical link with specific types of DNA damage.
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