An organ system-based approach to prognosis in advanced melanoma

Shernan G. Holtan, Aaron S. Mansfield, Douglas J. Creedon, Wendy K. Nevala, Paul Haluska, Alexey A. Leontovich, Svetomir N. Markovic

Research output: Contribution to journalArticlepeer-review

6 Scopus citations


Previous models to study the biology of melanoma have focused on individual factors, such as proliferative and invasive capacity, the microenvironment, angiogenesis, or systemic immune dysfunction. However, all of these factors contribute to melanoma progression in concert. One physiologic phenomenon that typifies the coordination of these processes is placental development, characterized by trophoblast proliferation, invasion into decidual tissues, angiogenesis, and transient organ systembased immune evasion. Herein, we explore expression of 34 proteins involved in placentation and determine their association with an established prognostic factor, tumor infiltrating lymphocytes (TILs), in a 118-patient tumor microarray (TMA). Melanoma expression of CD58 and galectin-9 independently predicted for a favorable prognosis. Patients could be categorized into three clusters based upon patterns of protein expression and TILs. Patients in Cluster 2 demonstrated frequent TILs and superior overall survival. Pathway enrichment using MetaCore from GeneGo, a Thompson Reuters company, showed that TIMP2 and CD44 were expressed more frequently within Cluster 2 patients, suggesting a potential association with TILs. A subset of melanoma patients appear to lack an organized immune response to the tumor, which portends a poor prognosis.

Original languageEnglish (US)
Pages (from-to)2723-2733
Number of pages11
JournalFrontiers in Bioscience - Elite
Volume4 E
Issue number8
StatePublished - Jun 1 2012


  • B7H1-
  • CD44
  • CD58
  • Galectin-9
  • Melanoma
  • Placenta
  • Systems biology
  • TIMP2
  • Tissue microarray
  • Tumor infiltrating lymphocytes

ASJC Scopus subject areas

  • General Biochemistry, Genetics and Molecular Biology
  • General Immunology and Microbiology


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