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

Burdelski C, Strauss C, Tsourlakis MC, Kluth M, Hube-Magg C, Melling N, Lebok P, Minner S, Koop C, Graefen M, Heinzer H, Wittmer C, Krech T, Sauter G, Wilczak W, Simon R, Schlomm T, Steurer S - Oncotarget (2015)

Bottom Line: 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 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.

View Article: PubMed Central - PubMed

Affiliation: General, Visceral and Thoracic Surgery Department and Clinic, University Medical Center Hamburg-Eppendorf, Germany.

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.

No MeSH data available.


Related in: MedlinePlus

Representative images of TYMS immunostainings in prostate cancer(a) negative staining, (b) weak staining, (c) moderate staining, (d) strong staining.
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Figure 1: Representative images of TYMS immunostainings in prostate cancer(a) negative staining, (b) weak staining, (c) moderate staining, (d) strong staining.

Mentions: TYMS immunostaining was typically negative and sometimes weak in luminal cells of benign prostate glands, while basal cells were consistently negative. In prostate cancers, cytoplasmic TYMS staining was observed in 72.9% of 10,223 interpretable cancer cases. Detectable TYMS staining was considered weak in 17.6%, moderate in 33.4% and strong in 21.9% of cases. Representative images are given in Figure 1a–1d.


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

Burdelski C, Strauss C, Tsourlakis MC, Kluth M, Hube-Magg C, Melling N, Lebok P, Minner S, Koop C, Graefen M, Heinzer H, Wittmer C, Krech T, Sauter G, Wilczak W, Simon R, Schlomm T, Steurer S - Oncotarget (2015)

Representative images of TYMS immunostainings in prostate cancer(a) negative staining, (b) weak staining, (c) moderate staining, (d) strong staining.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4480759&req=5

Figure 1: Representative images of TYMS immunostainings in prostate cancer(a) negative staining, (b) weak staining, (c) moderate staining, (d) strong staining.
Mentions: TYMS immunostaining was typically negative and sometimes weak in luminal cells of benign prostate glands, while basal cells were consistently negative. In prostate cancers, cytoplasmic TYMS staining was observed in 72.9% of 10,223 interpretable cancer cases. Detectable TYMS staining was considered weak in 17.6%, moderate in 33.4% and strong in 21.9% of cases. Representative images are given in Figure 1a–1d.

Bottom Line: 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 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.

View Article: PubMed Central - PubMed

Affiliation: General, Visceral and Thoracic Surgery Department and Clinic, University Medical Center Hamburg-Eppendorf, Germany.

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.

No MeSH data available.


Related in: MedlinePlus