Pathologic and gene expression features of metastatic melanomas to the brain

Cancer. 2013 Aug 1;119(15):2737-46. doi: 10.1002/cncr.28029. Epub 2013 May 21.


Background: The prognosis of metastatic melanomas to the brain (MBM) is variable with prolonged survival in a subset. It is unclear whether MBM differ from extracranial metastases (EcM) and primary melanomas (PrM).

Methods: To study the biology of MBM, histopathologic analysis of tumor blocks from patients' craniotomy samples and whole-genome expression profiling (WGEP) with confirmatory immunohistochemistry were performed.

Results: High mononuclear infiltrate and low intratumoral hemorrhage were associated with prolonged overall survival (OS). Pathway analysis of WGEP data from 29 such craniotomy tumor blocks demonstrated that several immune-related BioCarta gene sets were associated with prolonged OS. WGEP analysis of MBM in comparison with same-patient EcM and PrM showed that MBM and EcM were similar, but both differ significantly from PrM. Immunohistochemical analysis revealed that peritumoral CD3⁺ and CD8⁺ cells were associated with prolonged OS.

Conclusions: MBMs are more similar to EcM compared with PrM. Immune infiltrate is a favorable prognostic factor for MBM.

Keywords: brain metastases; craniotomy immune infiltrate; gene expression profiling; melanoma.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Adolescent
  • Adult
  • Aged
  • Aged, 80 and over
  • Brain Neoplasms / genetics*
  • Brain Neoplasms / secondary*
  • Female
  • Gene Expression Profiling
  • Humans
  • Immunohistochemistry
  • In Situ Hybridization
  • Male
  • Melanoma / genetics*
  • Melanoma / pathology*
  • Middle Aged
  • Prognosis
  • Skin Neoplasms / genetics*
  • Skin Neoplasms / pathology*
  • Young Adult