Prostatic adenocarcinoma CNS parenchymal and dural metastases: alterations in ERG, CHD1 and MAP3K7 expression

J Neurooncol. 2019 Apr;142(2):319-325. doi: 10.1007/s11060-019-03099-x. Epub 2019 Jan 17.


Background: Prostatic carcinoma metastatic to dura is commonly encountered at autopsy, but presenting as a dural or, especially parenchymal, brain metastasis during life is far less common. Our group has been interested in two immunohistochemical (IHC) markers previously shown to be downregulated in particularly aggressive primary prostatic carcinomas: CHD1 and MAP3K7. Here we assess protein expression in clinically-relevant CNS metastases. We also assessed how these two markers correlated with the most common genetic alteration in prostate cancer: TMPRSS2 fusion to ERG (40-60% of carcinomas at the primary site), which places ERG expression under the control of the androgen-regulated TMPRSS2 gene, increasing expression.

Design: Database query, 2000-2016, identified 16 metastases to dura, 5 to brain parenchyma.

Results: Four of five intraparenchymal metastases and 15/16 informative dural-based metastases were ERG-negative (90.5% overall). There was reduced expression of CHD1 in 8/21 and reduced MAP3K7 in 17/21 cases; 7/19 (37%) ERG-negative metastases had dual low expression of CHD1/MAP3K7. ERG-positive cases had high expression of one or both markers.

Conclusion: Metastatic prostatic carcinoma to CNS demonstrates expression patterns consistent with particularly aggressive behavior. Lower ERG expression in dural and intraparenchymal metastases suggests a possibility that ERG-negative tumors with loss of MAP3K7 may become resistant to standard therapies and diffusely metastasize.

Keywords: Brain metastasis; CHD1; Dural metastasis; ERG; MAP3K7; Prostate cancer.

MeSH terms

  • Adenocarcinoma / metabolism
  • Adenocarcinoma / pathology*
  • Biomarkers, Tumor / metabolism
  • Brain Neoplasms / metabolism*
  • Brain Neoplasms / secondary*
  • DNA Helicases / metabolism
  • DNA-Binding Proteins / metabolism
  • Gene Expression Regulation, Neoplastic
  • Humans
  • MAP Kinase Kinase Kinases / metabolism
  • Male
  • Meningeal Neoplasms / metabolism*
  • Meningeal Neoplasms / secondary*
  • PTEN Phosphohydrolase / metabolism
  • Parenchymal Tissue
  • Prostatic Neoplasms / metabolism
  • Prostatic Neoplasms / pathology*
  • Retrospective Studies
  • Serine Endopeptidases / metabolism
  • Transcriptional Regulator ERG / metabolism


  • Biomarkers, Tumor
  • DNA-Binding Proteins
  • ERG protein, human
  • Transcriptional Regulator ERG
  • MAP Kinase Kinase Kinases
  • MAP kinase kinase kinase 7
  • PTEN Phosphohydrolase
  • PTEN protein, human
  • Serine Endopeptidases
  • TMPRSS2 protein, human
  • DNA Helicases
  • CHD1 protein, human