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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

Association between TYMS expression levels and ERG-fusion stateComparison of TYMS expression levels in ERG-positive and ERG-negative prostate cancers. ERG-fusion state was determined either by immunohistochemistry, or by FISH for ERG gene breakage.
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Figure 2: Association between TYMS expression levels and ERG-fusion stateComparison of TYMS expression levels in ERG-positive and ERG-negative prostate cancers. ERG-fusion state was determined either by immunohistochemistry, or by FISH for ERG gene breakage.

Mentions: Data on both TYMS staining and ERG status obtained by ERG-FISH were available in 5,712 patients and by ERG-IHC from 8,935 tumors. Strong TYMS staining was slightly more frequent in ERG-negative than in ERG-positive tumors both by FISH and by IHC. As the tumor sets were very large, statistical differences between the ERG positive and negative groups were still highly significant (p < 0.0001; Figure 2).


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)

Association between TYMS expression levels and ERG-fusion stateComparison of TYMS expression levels in ERG-positive and ERG-negative prostate cancers. ERG-fusion state was determined either by immunohistochemistry, or by FISH for ERG gene breakage.
© Copyright Policy - open-access
Related In: Results  -  Collection

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

Figure 2: Association between TYMS expression levels and ERG-fusion stateComparison of TYMS expression levels in ERG-positive and ERG-negative prostate cancers. ERG-fusion state was determined either by immunohistochemistry, or by FISH for ERG gene breakage.
Mentions: Data on both TYMS staining and ERG status obtained by ERG-FISH were available in 5,712 patients and by ERG-IHC from 8,935 tumors. Strong TYMS staining was slightly more frequent in ERG-negative than in ERG-positive tumors both by FISH and by IHC. As the tumor sets were very large, statistical differences between the ERG positive and negative groups were still highly significant (p < 0.0001; Figure 2).

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