Clinical Research Papers:

Overexpression of thymidylate synthase (TYMS) is associated with aggressive tumor features and early PSA recurrence in prostate cancer

Christoph Burdelski _, Christian Strauss, Maria Christina Tsourlakis, Martina Kluth, Claudia Hube-Magg, Nathaniel Melling, Patrick Lebok, Sarah Minner, Christina Koop, Markus Graefen, Hans Heinzer, Corinna Wittmer, Till Krech, Guido Sauter, Waldemar Wilczak, Ronald Simon, Thorsten Schlomm and Stefan Steurer

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Oncotarget. 2015; 6:8377-8387. https://doi.org/10.18632/oncotarget.3107

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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

Correspondence to:

Ronald Simon, e-mail: [email protected]

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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