TMPRSS2-ERG expression predicts prostate cancer survival and associates with stromal biomarkers

Christina Hägglöf; Peter Hammarsten; Kerstin Strömvall; Lars Egevad; Andreas Josefsson; Pär Stattin; Torvald Granfors; Anders Bergh

doi:10.1371/journal.pone.0086824

TMPRSS2-ERG expression predicts prostate cancer survival and associates with stromal biomarkers

PLoS One. 2014 Feb 5;9(2):e86824. doi: 10.1371/journal.pone.0086824. eCollection 2014.

Authors

Christina Hägglöf¹, Peter Hammarsten¹, Kerstin Strömvall¹, Lars Egevad², Andreas Josefsson³, Pär Stattin⁴, Torvald Granfors⁵, Anders Bergh¹

Affiliations

¹ Department of Medical Biosciences, Umeå University, Umeå, Sweden.
² Department of Oncology-Pathology, Karolinska Institutet, Stockholm, Sweden.
³ Department of Urology, University of Gothenburg, Gothenburg, Sweden.
⁴ Departments of Surgery and Perioperative Sciences, Umeå University, Umeå, Sweden.
⁵ Department of Urology, Västerås Central Hospital, Västerås, Sweden.

Abstract

The TMPRSS2-ERG gene fusion is found in approximately half of all prostate cancers. The functional and prognostic significance of TMPRSS2-ERG is, however, not fully understood. Based on a historical watchful waiting cohort, an association between TMPRSS2-ERG, evaluated as positive immune staining, and shorter survival of prostate cancer patients was identified. Expression of ERG was also associated with clinical markers such as advanced tumor stage, high Gleason score, presence of metastasis and prognostic tumor cell markers such as high Ki67, pEGFR and pAkt. Novel associations between TMPRSS2-ERG and alterations in the tumor stroma, for example, increased vascular density, hyaluronan and PDGFRβ and decreased Caveolin-1, all known to be associated with an aggressive disease, were found. The present study suggests that the TMPRSS2-ERG fusion gene is associated with a more aggressive prostate cancer phenotype, supported by changes in the tumor stroma.

Publication types

Clinical Trial
Research Support, Non-U.S. Gov't

MeSH terms

Caveolin 1 / biosynthesis
Disease-Free Survival
Early Growth Response Protein 1 / biosynthesis*
ErbB Receptors / biosynthesis
Gene Expression Regulation, Neoplastic*
Humans
Ki-67 Antigen / biosynthesis
Male
Oncogene Proteins, Fusion / biosynthesis*
Prostatic Neoplasms / metabolism*
Prostatic Neoplasms / mortality*
Prostatic Neoplasms / pathology
Prostatic Neoplasms / therapy
Proto-Oncogene Proteins c-akt / biosynthesis
Serine Endopeptidases / biosynthesis*
Survival Rate

Substances

CAV1 protein, human
Caveolin 1
EGR1 protein, human
Early Growth Response Protein 1
Ki-67 Antigen
Oncogene Proteins, Fusion
EGFR protein, human
ErbB Receptors
Proto-Oncogene Proteins c-akt
Serine Endopeptidases
TMPRSS2 protein, human

Grants and funding

The Swedish Research Council and the Swedish Cancer Society supported the work. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.