TY - JOUR
T1 - Immune profile and mitotic index of metastatic melanoma lesions enhance clinical staging in predicting patient survival
AU - Bogunovic, Dusan
AU - O'Neill, David W.
AU - Belitskaya-Levy, Ilana
AU - Vacic, Vladimir
AU - Yu, Yi Lo
AU - Adams, Sylvia
AU - Darvishian, Farbod
AU - Berman, Russell
AU - Shapiro, Richard
AU - Pavlick, Anna C.
AU - Lonardi, Stefano
AU - Zavadil, Jiri
AU - Osman, Iman
AU - Bhardwaj, Nina
PY - 2009/12/1
Y1 - 2009/12/1
N2 - 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.
AB - 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.
KW - Gene expression analysis
KW - Immune response
KW - TNM staging
KW - Tumor infiltrating leukocytes
UR - http://www.scopus.com/inward/record.url?scp=73949140415&partnerID=8YFLogxK
U2 - 10.1073/pnas.0905139106
DO - 10.1073/pnas.0905139106
M3 - Article
C2 - 19915147
AN - SCOPUS:73949140415
SN - 0027-8424
VL - 106
SP - 20429
EP - 20434
JO - Proceedings of the National Academy of Sciences of the United States of America
JF - Proceedings of the National Academy of Sciences of the United States of America
IS - 48
ER -