A systematic literature review and meta-analysis of published studies found several promising markers associated with clinical outcome in early-stage melanoma patients. However, the review also revealed that numerous published reports did not meet the minimum guidelines established in 2005 for biomarker studies.
Some patients with early stage melanoma can be treated with surgery alone. However, biomarkers that distinguish these patients from patients who will have recurrent disease have not emerged, despite numerous reports of putative markers in the literature.
To better understand why this disconnect exists, Bonnie Gould Rothberg, M.D., of the Yale University School of Medicine in New Haven, Conn., and colleagues performed a systematic literature review and meta-analysis of studies that reported on putative protein biomarkers associated with clinical outcome in patients with early melanoma. The investigators restricted their analysis to studies that used immunohistochemistry-based biomarker detection.
The team initially identified 102 cohort studies in the literature, but only 37 met all of their inclusion criteria. Twenty-seven studies were excluded by the investigators because they lacked adequate methodological information, despite having been published after 2005, when the medical research community established minimum guidelines for publication of biomarker studies, called REMARK.
The thirty-seven studies that met the inclusion criteria for the meta-analysis evaluated 62 protein markers. Several promising markers emerged, including MCAM/MUC18, matrix metalloproteinase-2, Ki-67, PCNA, and p16/INK4A.
"This systematic review…supports involvement of cyclin-dependent kinase inhibitors, effectors of DNA replication and cell proliferation, growth-promoting transcription factors, and multiple regulators of tissue invasion and metastasis (the latter including cell-adhesion molecules, matricellular proteins, and selected matrix metalloproteinases) in modulating melanoma outcomes," the authors conclude. "These results, however, need to be validated in adequately powered prospective studies."
The research is published in the March 24 online issue of the Journal of the National Cancer Institute.
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