Abstract
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.
Highlights
Prostate cancer is the most prevalent cancer in men in Western societies [1]
The results of our study demonstrate that Thymidylate synthase (TYMS) overexpression is strongly linked to the subset of aggressive prostate cancers characterized by early prostate-specific antigen (PSA) recurrence and molecular features of chromosomal instability
The analysis revealed a strong association between high TYMS expression and 5q21 and 6q15 deletions (p < 0.0001, each) and a weaker association between high TYMS expression and 3p13 deletion (p = 0.0083), while TYMS expression was completely unrelated to PTEN deletion (Figure 3a)
Summary
The majority of these cancers represent low-malignant tumors with an indolent clinical behavior, some do progress to aggressive and potentially life-threatening disease. Distinguishing between these two appearances of prostate cancer remains difficult [2]. The only established prognostic parameters that are available prior to treatment decisions include Gleason grade and tumor extent on biopsies, prostate-specific antigen (PSA) levels, and clinical stage. Statistically powerful, these parameters are not sufficient for individual treatment decisions, and overtreatment is a frequent issue for prostate cancer patients. It can be hoped that a better understanding of disease biology will eventually lead to the identification of clinically applicable molecular markers that enable a more reliable prediction of prostate cancer aggressiveness
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Free) 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a call
