Increased ERCC1 expression is linked to chromosomal aberrations and adverse tumor biology in prostate cancer
Abstract Background Animal model experiments have suggested a role of the DNA repair protein ERCC1 (Excision Repair Cross-Complementation Group 1) in prostate cancer progression. Methods To better understand the impact of ERCC1 protein expression in human prostate cancer, a preexisting tissue microa...
| Main Authors: | , , , , , , , , , , , , , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
BMC
2017-07-01
|
| Series: | BMC Cancer |
| Subjects: | |
| Online Access: | http://link.springer.com/article/10.1186/s12885-017-3489-9 |
| _version_ | 1818328197080547328 |
|---|---|
| author | Frank Jacobsen Billurvan Taskin Nathaniel Melling Charlotte Sauer Corinna Wittmer Claudia Hube-Magg Martina Kluth Ronald Simon Dirk Pehrke Burkhard Beyer Thomas Steuber Imke Thederan Guido Sauter Thorsten Schlomm Waldemar Wilczak Katharina Möller Sören A. Weidemann Susanne Burdak-Rothkamm |
| author_facet | Frank Jacobsen Billurvan Taskin Nathaniel Melling Charlotte Sauer Corinna Wittmer Claudia Hube-Magg Martina Kluth Ronald Simon Dirk Pehrke Burkhard Beyer Thomas Steuber Imke Thederan Guido Sauter Thorsten Schlomm Waldemar Wilczak Katharina Möller Sören A. Weidemann Susanne Burdak-Rothkamm |
| author_sort | Frank Jacobsen |
| collection | DOAJ |
| description | Abstract Background Animal model experiments have suggested a role of the DNA repair protein ERCC1 (Excision Repair Cross-Complementation Group 1) in prostate cancer progression. Methods To better understand the impact of ERCC1 protein expression in human prostate cancer, a preexisting tissue microarray (TMA) containing more than 12,000 prostate cancer specimens was analyzed by immunohistochemistry and data were compared with tumor phenotype, PSA recurrence and several of the most common genomic alterations (TMPRSS2:ERG fusions: deletions of PTEN, 6q, 5q, 3p). Results ERCC1 staining was seen in 64.7% of 10,436 interpretable tissues and was considered weak in 37.1%, moderate in 22.6% and strong in 5% of tumors. High-level ERCC1 staining was linked to advanced pT stage, high Gleason grade, positive lymph nodes, high pre-operative serum PSA, and positive surgical margin status (p < 0.0001 each). High ERCC1 expression was strongly associated with an elevated risk of PSA recurrence (p < 0.0001). This was independent of established prognostic features. A subgroup analysis of cancers defined by comparable quantitative Gleason grades revealed that the prognostic impact was mostly driven by low-grade tumors with a Gleason 3 + 3 or 3 + 4 (Gleason 4: ≤5%). High ERCC1 expression was strongly associated with the presence of genomic alterations and expression levels increased with the number of deletions present in the tumor. These latter data suggest a functional relationship of ERCC1 expression with genomic instability. Conclusion The results of our study demonstrate that expression of ERCC1 - a potential surrogate for genomic instability - is an independent prognostic marker in prostate cancer with particular importance in low-grade tumors. |
| first_indexed | 2024-12-13T12:28:20Z |
| format | Article |
| id | doaj.art-c2dfda6de6ee4ff5b74f18521aae0709 |
| institution | Directory Open Access Journal |
| issn | 1471-2407 |
| language | English |
| last_indexed | 2024-12-13T12:28:20Z |
| publishDate | 2017-07-01 |
| publisher | BMC |
| record_format | Article |
| series | BMC Cancer |
| spelling | doaj.art-c2dfda6de6ee4ff5b74f18521aae07092022-12-21T23:46:10ZengBMCBMC Cancer1471-24072017-07-0117111110.1186/s12885-017-3489-9Increased ERCC1 expression is linked to chromosomal aberrations and adverse tumor biology in prostate cancerFrank Jacobsen0Billurvan Taskin1Nathaniel Melling2Charlotte Sauer3Corinna Wittmer4Claudia Hube-Magg5Martina Kluth6Ronald Simon7Dirk Pehrke8Burkhard Beyer9Thomas Steuber10Imke Thederan11Guido Sauter12Thorsten Schlomm13Waldemar Wilczak14Katharina Möller15Sören A. Weidemann16Susanne Burdak-Rothkamm17Institute of Pathology, University Medical Center Hamburg-EppendorfInstitute of Pathology, University Medical Center Hamburg-EppendorfGeneral, Visceral and Thoracic Surgery Department and Clinic, University Medical Center Hamburg-EppendorfInstitute of Pathology, University Medical Center Hamburg-EppendorfInstitute of Pathology, University Medical Center Hamburg-EppendorfInstitute of Pathology, University Medical Center Hamburg-EppendorfInstitute of Pathology, University Medical Center Hamburg-EppendorfInstitute of Pathology, University Medical Center Hamburg-EppendorfMartini-Clinic, Prostate Cancer Center, University Medical Center Hamburg-EppendorfMartini-Clinic, Prostate Cancer Center, University Medical Center Hamburg-EppendorfMartini-Clinic, Prostate Cancer Center, University Medical Center Hamburg-EppendorfMartini-Clinic, Prostate Cancer Center, University Medical Center Hamburg-EppendorfInstitute of Pathology, University Medical Center Hamburg-EppendorfMartini-Clinic, Prostate Cancer Center, University Medical Center Hamburg-EppendorfInstitute of Pathology, University Medical Center Hamburg-EppendorfInstitute of Pathology, University Medical Center Hamburg-EppendorfInstitute of Pathology, University Medical Center Hamburg-EppendorfInstitute of Pathology, University Medical Center Hamburg-EppendorfAbstract Background Animal model experiments have suggested a role of the DNA repair protein ERCC1 (Excision Repair Cross-Complementation Group 1) in prostate cancer progression. Methods To better understand the impact of ERCC1 protein expression in human prostate cancer, a preexisting tissue microarray (TMA) containing more than 12,000 prostate cancer specimens was analyzed by immunohistochemistry and data were compared with tumor phenotype, PSA recurrence and several of the most common genomic alterations (TMPRSS2:ERG fusions: deletions of PTEN, 6q, 5q, 3p). Results ERCC1 staining was seen in 64.7% of 10,436 interpretable tissues and was considered weak in 37.1%, moderate in 22.6% and strong in 5% of tumors. High-level ERCC1 staining was linked to advanced pT stage, high Gleason grade, positive lymph nodes, high pre-operative serum PSA, and positive surgical margin status (p < 0.0001 each). High ERCC1 expression was strongly associated with an elevated risk of PSA recurrence (p < 0.0001). This was independent of established prognostic features. A subgroup analysis of cancers defined by comparable quantitative Gleason grades revealed that the prognostic impact was mostly driven by low-grade tumors with a Gleason 3 + 3 or 3 + 4 (Gleason 4: ≤5%). High ERCC1 expression was strongly associated with the presence of genomic alterations and expression levels increased with the number of deletions present in the tumor. These latter data suggest a functional relationship of ERCC1 expression with genomic instability. Conclusion The results of our study demonstrate that expression of ERCC1 - a potential surrogate for genomic instability - is an independent prognostic marker in prostate cancer with particular importance in low-grade tumors.http://link.springer.com/article/10.1186/s12885-017-3489-9ERCC1DNA repairProstate cancerPrognosis |
| spellingShingle | Frank Jacobsen Billurvan Taskin Nathaniel Melling Charlotte Sauer Corinna Wittmer Claudia Hube-Magg Martina Kluth Ronald Simon Dirk Pehrke Burkhard Beyer Thomas Steuber Imke Thederan Guido Sauter Thorsten Schlomm Waldemar Wilczak Katharina Möller Sören A. Weidemann Susanne Burdak-Rothkamm Increased ERCC1 expression is linked to chromosomal aberrations and adverse tumor biology in prostate cancer BMC Cancer ERCC1 DNA repair Prostate cancer Prognosis |
| title | Increased ERCC1 expression is linked to chromosomal aberrations and adverse tumor biology in prostate cancer |
| title_full | Increased ERCC1 expression is linked to chromosomal aberrations and adverse tumor biology in prostate cancer |
| title_fullStr | Increased ERCC1 expression is linked to chromosomal aberrations and adverse tumor biology in prostate cancer |
| title_full_unstemmed | Increased ERCC1 expression is linked to chromosomal aberrations and adverse tumor biology in prostate cancer |
| title_short | Increased ERCC1 expression is linked to chromosomal aberrations and adverse tumor biology in prostate cancer |
| title_sort | increased ercc1 expression is linked to chromosomal aberrations and adverse tumor biology in prostate cancer |
| topic | ERCC1 DNA repair Prostate cancer Prognosis |
| url | http://link.springer.com/article/10.1186/s12885-017-3489-9 |
| work_keys_str_mv | AT frankjacobsen increasedercc1expressionislinkedtochromosomalaberrationsandadversetumorbiologyinprostatecancer AT billurvantaskin increasedercc1expressionislinkedtochromosomalaberrationsandadversetumorbiologyinprostatecancer AT nathanielmelling increasedercc1expressionislinkedtochromosomalaberrationsandadversetumorbiologyinprostatecancer AT charlottesauer increasedercc1expressionislinkedtochromosomalaberrationsandadversetumorbiologyinprostatecancer AT corinnawittmer increasedercc1expressionislinkedtochromosomalaberrationsandadversetumorbiologyinprostatecancer AT claudiahubemagg increasedercc1expressionislinkedtochromosomalaberrationsandadversetumorbiologyinprostatecancer AT martinakluth increasedercc1expressionislinkedtochromosomalaberrationsandadversetumorbiologyinprostatecancer AT ronaldsimon increasedercc1expressionislinkedtochromosomalaberrationsandadversetumorbiologyinprostatecancer AT dirkpehrke increasedercc1expressionislinkedtochromosomalaberrationsandadversetumorbiologyinprostatecancer AT burkhardbeyer increasedercc1expressionislinkedtochromosomalaberrationsandadversetumorbiologyinprostatecancer AT thomassteuber increasedercc1expressionislinkedtochromosomalaberrationsandadversetumorbiologyinprostatecancer AT imkethederan increasedercc1expressionislinkedtochromosomalaberrationsandadversetumorbiologyinprostatecancer AT guidosauter increasedercc1expressionislinkedtochromosomalaberrationsandadversetumorbiologyinprostatecancer AT thorstenschlomm increasedercc1expressionislinkedtochromosomalaberrationsandadversetumorbiologyinprostatecancer AT waldemarwilczak increasedercc1expressionislinkedtochromosomalaberrationsandadversetumorbiologyinprostatecancer AT katharinamoller increasedercc1expressionislinkedtochromosomalaberrationsandadversetumorbiologyinprostatecancer AT sorenaweidemann increasedercc1expressionislinkedtochromosomalaberrationsandadversetumorbiologyinprostatecancer AT susanneburdakrothkamm increasedercc1expressionislinkedtochromosomalaberrationsandadversetumorbiologyinprostatecancer |