Morphological features of TMPRSS2-ERG gene fusion prostate cancer

J. M. Mosquera, S. Perner, F. Demichelis, R. Kim, M. D. Hofer, K. D. Mertz, P. L. Paris, J. Simko, C. Collins, T. A. Bismar, A. M. Chinnaiyan, M. A. Rubin*

*Corresponding author for this work

Research output: Contribution to journalArticle

101 Scopus citations

Abstract

The TMPRSS2-ETS fusion prostate cancers comprise 50-70% of the prostate-specific antigen (PSA)-screened hospital-based prostate cancers examined to date, making it perhaps the most common genetic rearrangement in human cancer. The most common variant involves androgen-regulated TMPRSS2 and ERG, both located on chromosome 21. Emerging data from our group and others suggests that TMPRSS2-ERG fusion prostate cancer is associated with higher tumour stage and prostate cancer-specific death. The goal of this study was to determine if this common somatic alteration is associated with a morphological phenotype. We assessed 253 prostate cancer cases for TMPRSS2-ERG fusion status using an ERG break-apart FISH assay. Blinded to gene fusion status, two reviewers assessed each tumour for presence or absence of eight morphological features. Statistical analysis was performed to look for significant associations between morphological features and TMPRSS2-ERG fusion status. Five morphological features were associated with TMPRSS2-ERG fusion prostate cancer: blue-tinged mucin, cribriform growth pattern, macronucleoli, intraductal tumour spread, and signet-ring cell features, all with p-values <0.05. Only 24% (n = 30/125) of tumours without any of these features displayed the TMPRSS2-ERG fusion. By comparison, 55% (n = 38/69) of cases with one feature (RR = 3.88), 86% (n = 38/44) of cases with two features (RR = 20.06), and 93% (n = 14/15) of cases with three or more features (RR = 44.33) were fusion positive (p < 0.001). To our knowledge, this is the first study that demonstrates a significant link between a molecular alteration in prostate cancer and distinct phenotypic features. The strength of these findings is similar to microsatellite unstable colon cancer and breast cancer involving BRCA1 and BRCA2 mutations. The biological effect of TMPRSS2-ERG overexpression may drive pathways that favour these common morphological features that pathologists observe daily. These features may also be helpful in diagnosing TMPRSS2-ERG fusion prostate cancer, which may have both prognostic and therapeutic implications.

Original languageEnglish (US)
Pages (from-to)91-101
Number of pages11
JournalJournal of Pathology
Volume212
Issue number1
DOIs
StatePublished - May 1 2007

Keywords

  • Bluetinged mucin
  • Collagenous micronodules
  • Cribriform growth pattern
  • Fluorescence in situ hybridization (FISH)
  • Gene fusion
  • Intraductal tumour spread
  • Macronucleoli
  • Signet-ring cell features
  • Translocation

ASJC Scopus subject areas

  • Pathology and Forensic Medicine

Fingerprint Dive into the research topics of 'Morphological features of TMPRSS2-ERG gene fusion prostate cancer'. Together they form a unique fingerprint.

  • Cite this

    Mosquera, J. M., Perner, S., Demichelis, F., Kim, R., Hofer, M. D., Mertz, K. D., Paris, P. L., Simko, J., Collins, C., Bismar, T. A., Chinnaiyan, A. M., & Rubin, M. A. (2007). Morphological features of TMPRSS2-ERG gene fusion prostate cancer. Journal of Pathology, 212(1), 91-101. https://doi.org/10.1002/path.2154