Immune profile and mitotic index of metastatic melanoma lesions enhance clinical staging in predicting patient survival

Dusan Bogunovic, David W. O'Neill, Ilana Belitskaya-Levy, Vladimir Vacic, Yi Lo Yu, Sylvia Adams, Farbod Darvishian, Russell Berman, Richard Shapiro, Anna C. Pavlick, Stefano Lonardi, Jiri Zavadil, Iman Osman, Nina Bhardwaj

Research output: Contribution to journalArticlepeer-review

295 Scopus citations

Abstract

Although remission rates for metastatic melanoma are generally very poor, some patients can survive for prolonged periods following metastasis. We used gene expression profiling, mitotic index (MI), and quantification of tumor infiltrating leukocytes (TILs) and CD3+ cells in metastatic lesions to search for a molecular basis for this observation and to develop improved methods for predicting patient survival. We identified a group of 266 genes associated with postrecurrence survival. Genes positively associated with survival were predominantly immune response related (e.g., ICOS, CD3d, ZAP70, TRAT1, TARP, GZMK, LCK, CD2, CXCL13, CCL19, CCR7, VCAM1) while genes negatively associated with survival were cell proliferation related (e.g., PDE4D, CDK2, GREF1, NUSAP1, SPC24). Furthermore, any of the 4 parameters (prevalidated gene expression signature, TILs, CD3, and in particular MI) improved the ability of Tumor, Node, Metastasis (TNM) staging to predict postrecurrence survival; MI was the most significant contributor (HR = 2.13, P = 0.0008). An immune response gene expression signature and presence of TILs and CD3+ cells signify immune surveillance as a mechanism for prolonged survival in these patients and indicate improved patient subcategorization beyond current TNM staging.

Original languageEnglish
Pages (from-to)20429-20434
Number of pages6
JournalProceedings of the National Academy of Sciences of the United States of America
Volume106
Issue number48
DOIs
StatePublished - 1 Dec 2009
Externally publishedYes

Keywords

  • Gene expression analysis
  • Immune response
  • TNM staging
  • Tumor infiltrating leukocytes

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