Expression of DNA ligase IV is linked to poor prognosis and characterizes a subset of prostate cancers harboring TMPRSS2:ERG fusion and PTEN deletion

  • Authors:
    • Katharina Grupp
    • Laura Roettger
    • Martina Kluth
    • Claudia Hube-Magg
    • Ronald Simon
    • Patrick Lebok
    • Sarah Minner
    • Maria Christina Tsourlakis
    • Christina Koop
    • Markus Graefen
    • Meike Adam
    • Alexander Haese
    • Corinna Wittmer
    • Guido Sauter
    • Waldemar Wilczak
    • Hartwig Huland
    • Thorsten Schlomm
    • Stefan Steurer
    • Till Krech
  • View Affiliations

  • Published online on: June 25, 2015     https://doi.org/10.3892/or.2015.4080
  • Pages: 1211-1220
Metrics: Total Views: 0 (Spandidos Publications: | PMC Statistics: )
Total PDF Downloads: 0 (Spandidos Publications: | PMC Statistics: )


Abstract

DNA ligases are essential for the maintenance of genome integrity as they are indispensable for DNA replication, recombination and repair. The present study was undertaken to gain insights into the prevalence and clinical significance of ligase IV (LIG4) expression in prostate cancer. A total of 11,152 prostate cancer specimens were analyzed by immunohistochemistry for LIG4 expression. Results were compared to follow-up data, ERG status and deletions at PTEN, 3p13, 5q21 and 6q15. LIG4 expression was predominantly localized in the nucleus of the cells with increased intensities in malignant as compared to benign prostate epithelium. In prostate cancer, LIG4 expression was found in 91% of interpretable tumors, including 12% cancers with weak, 23% with moderate and 56% with strong LIG4 positivity. Strong LIG4 expression was tightly linked to advanced Gleason score (P<0.0001) and positive nodal involvement (P=0.03). There was a remarkable accumulation of strong LIG4 expression in tumors harboring TMPRSS2:ERG fusion and PTEN deletions (P<0.0001 each). High LIG4 expression was also tightly related to early biochemical recurrence when all tumors (P<0.0001) or the subsets of ERG-negative (P=0.0004) or ERG-positive prostate cancers (P=0.006) were analyzed. Multivariate analysis including parameters that are available before surgery demonstrated independent association with biochemical recurrence for advanced Gleason grade on biopsy, high preoperative PSA level, high clinical stage (P<0.0001 each) and for LIG4 immunostaining (P=0.03). Our study identifies LIG4 as a predictor of an increased risk for early PSA recurrence in prostate cancer. Moreover, the strong association with TMPRSS2:ERG fusion and PTEN deletions suggest important interactions between these pathways in prostate cancers.
View Figures
View References

Related Articles

Journal Cover

September-2015
Volume 34 Issue 3

Print ISSN: 1021-335X
Online ISSN:1791-2431

Sign up for eToc alerts

Recommend to Library

Copy and paste a formatted citation
x
Spandidos Publications style
Grupp K, Roettger L, Kluth M, Hube-Magg C, Simon R, Lebok P, Minner S, Tsourlakis MC, Koop C, Graefen M, Graefen M, et al: Expression of DNA ligase IV is linked to poor prognosis and characterizes a subset of prostate cancers harboring TMPRSS2:ERG fusion and PTEN deletion. Oncol Rep 34: 1211-1220, 2015
APA
Grupp, K., Roettger, L., Kluth, M., Hube-Magg, C., Simon, R., Lebok, P. ... Krech, T. (2015). Expression of DNA ligase IV is linked to poor prognosis and characterizes a subset of prostate cancers harboring TMPRSS2:ERG fusion and PTEN deletion. Oncology Reports, 34, 1211-1220. https://doi.org/10.3892/or.2015.4080
MLA
Grupp, K., Roettger, L., Kluth, M., Hube-Magg, C., Simon, R., Lebok, P., Minner, S., Tsourlakis, M. C., Koop, C., Graefen, M., Adam, M., Haese, A., Wittmer, C., Sauter, G., Wilczak, W., Huland, H., Schlomm, T., Steurer, S., Krech, T."Expression of DNA ligase IV is linked to poor prognosis and characterizes a subset of prostate cancers harboring TMPRSS2:ERG fusion and PTEN deletion". Oncology Reports 34.3 (2015): 1211-1220.
Chicago
Grupp, K., Roettger, L., Kluth, M., Hube-Magg, C., Simon, R., Lebok, P., Minner, S., Tsourlakis, M. C., Koop, C., Graefen, M., Adam, M., Haese, A., Wittmer, C., Sauter, G., Wilczak, W., Huland, H., Schlomm, T., Steurer, S., Krech, T."Expression of DNA ligase IV is linked to poor prognosis and characterizes a subset of prostate cancers harboring TMPRSS2:ERG fusion and PTEN deletion". Oncology Reports 34, no. 3 (2015): 1211-1220. https://doi.org/10.3892/or.2015.4080