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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

Impact of different levels of TYMS expression on PSA recurrence free survival in molecularly defined subsets of prostate cancer(a) All cancers. (b) Subset of ERG-fusion negative cancers. (c) Subset of ERG-fusion positive prostate cancers. (d) Subset of cancers without deletions of 3p13, 5q21, and 6q15. (e) Subset of cancers harboring one or more of these deletions.
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Figure 4: Impact of different levels of TYMS expression on PSA recurrence free survival in molecularly defined subsets of prostate cancer(a) All cancers. (b) Subset of ERG-fusion negative cancers. (c) Subset of ERG-fusion positive prostate cancers. (d) Subset of cancers without deletions of 3p13, 5q21, and 6q15. (e) Subset of cancers harboring one or more of these deletions.

Mentions: High TYMS expression levels were associated with unfavorable tumor phenotype (Table 1). Significant associations were found with tumor stage, Gleason grade, preoperative PSA and surgical margin (p < 0.0001, each). High TYMS expression level was also associated with a higher risk for biochemical recurrence (Figure 4a, p < 0.0001). There was no major difference between ERG positive and ERG negative cancers in their relationship with PSA recurrence (Figure 4b–4c) and tumor phenotype (Supplementary Tables 2–3). Because of the strong link between TYMS and deletions of 3p, 5q, and 6q - which are all linked to poor prognosis [20, 21, 23] - separate subgroup analyses were also performed in cancers without these deletions (Figure 4d–4e), as well as in cancers harboring at least one of the three deletions (Figure 4e). The analysis revealed, that the prognostic value of high TYMS expression was independent from these deletions.


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)

Impact of different levels of TYMS expression on PSA recurrence free survival in molecularly defined subsets of prostate cancer(a) All cancers. (b) Subset of ERG-fusion negative cancers. (c) Subset of ERG-fusion positive prostate cancers. (d) Subset of cancers without deletions of 3p13, 5q21, and 6q15. (e) Subset of cancers harboring one or more of these deletions.
© Copyright Policy - open-access
Related In: Results  -  Collection

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

Figure 4: Impact of different levels of TYMS expression on PSA recurrence free survival in molecularly defined subsets of prostate cancer(a) All cancers. (b) Subset of ERG-fusion negative cancers. (c) Subset of ERG-fusion positive prostate cancers. (d) Subset of cancers without deletions of 3p13, 5q21, and 6q15. (e) Subset of cancers harboring one or more of these deletions.
Mentions: High TYMS expression levels were associated with unfavorable tumor phenotype (Table 1). Significant associations were found with tumor stage, Gleason grade, preoperative PSA and surgical margin (p < 0.0001, each). High TYMS expression level was also associated with a higher risk for biochemical recurrence (Figure 4a, p < 0.0001). There was no major difference between ERG positive and ERG negative cancers in their relationship with PSA recurrence (Figure 4b–4c) and tumor phenotype (Supplementary Tables 2–3). Because of the strong link between TYMS and deletions of 3p, 5q, and 6q - which are all linked to poor prognosis [20, 21, 23] - separate subgroup analyses were also performed in cancers without these deletions (Figure 4d–4e), as well as in cancers harboring at least one of the three deletions (Figure 4e). The analysis revealed, that the prognostic value of high TYMS expression was independent from these deletions.

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