Journal of the National Cancer Institute Advance Access originally published online on March 24, 2009
JNCI Journal of the National Cancer Institute 2009 101(7):452-474; doi:10.1093/jnci/djp038
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© The Author 2009. Published by Oxford University Press.
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Tissue Biomarkers for Prognosis in Cutaneous Melanoma: A Systematic Review and Meta-analysis
Affiliations of authors: Department of Pathology (BEGR, DLR) and Department of Epidemiology and Public Health (BEGR, MBB), Yale University School of Medicine, New Haven, CT
Correspondence to: David L. Rimm, MD, PhD, Department of Pathology, Yale University School of Medicine, 310 Cedar St, PO Box 208023, New Haven, CT 06520-8023 (e-mail: david.rimm{at}yale.edu).
In the clinical management of early-stage cutaneous melanoma, it is critical to determine which patients are cured by surgery alone and which should be treated with adjuvant therapy. To assist in this decision, many groups have made an effort to use molecular information. However, although there are hundreds of studies that have sought to assess the potential prognostic value of molecular markers in predicting the course of cutaneous melanoma, at this time, no molecular method to improve risk stratification is part of recommended clinical practice. To help understand this disconnect, we conducted a systematic review and meta-analysis of the published literature that reported immunohistochemistry-based protein biomarkers of melanoma outcome. Three parallel search strategies were applied to the PubMed database through January 15, 2008, to identify cohort studies that reported associations between immunohistochemical expression and survival outcomes in melanoma that conformed to the REMARK criteria. Of the 102 cohort studies, we identified only 37 manuscripts, collectively describing 87 assays on 62 distinct proteins, which met all inclusion criteria. Promising markers that emerged included melanoma cell adhesion molecule (MCAM)/MUC18 (all-cause mortality [ACM] hazard ratio [HR] = 16.34; 95% confidence interval [CI] = 3.80 to 70.28), matrix metalloproteinase-2 (melanoma-specific mortality [MSM] HR = 2.6; 95% CI = 1.32 to 5.07), Ki-67 (combined ACM HR = 2.66; 95% CI = 1.41 to 5.01), proliferating cell nuclear antigen (ACM HR = 2.27; 95% CI = 1.56 to 3.31), and p16/INK4A (ACM HR = 0.29; 95% CI = 0.10 to 0.83, MSM HR = 0.4; 95% CI = 0.24 to 0.67). We further noted incomplete adherence to the REMARK guidelines: 14 of 27 cohort studies that failed to adequately report their methods and nine studies that failed to either perform multivariable analyses or report their risk estimates were published since 2005.
Manuscript received July 23, 2008; revised January 27, 2009; accepted February 2, 2009.
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J Natl Cancer Inst 2009 101: 437.