Unique Genes in Tumor-Positive Sentinel Lymph Nodes Associated with Nonsentinel Lymph Node Metastases in Melanoma
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Current risk assessment tools to estimate the risk of nonsentinel lymph node metastases after completion lymphadenectomy for a positive sentinel lymph node (SLN) biopsy in cutaneous melanoma are based on clinical and pathologic factors. We identified a novel genetic signature that can predict non-SLN metastases in patients with cutaneous melanoma staged with a SLN biopsy.
RNA was collected for tumor-positive SLNs in patients staged by SLN biopsy for cutaneous melanoma. All patients with a tumor-positive SLN biopsy underwent completion lymphadenectomy. A 1:10 case:control series of positive and negative non-SLN patients was analyzed by microarray and quantitative RT-PCR. Candidate differentially expressed genes were validated in a 1:3 case:control separate cohort of positive and negative non-SLN patients.
The 1:10 case:control discovery set consisted of 7 positive non-SLN cases matched to 70 negative non-SLN controls. The cases and controls were similar with regards to important clinicopathologic factors, such as gender, primary tumor site, age, ulceration, and thickness. Microarray and RT-PCR identified six potential differentially expressed genes for validation. In the 40-patient separate validation set, 10 positive non-SLN patients were matched to 30 negative non-SLN controls based on gender, ulceration, age, and thickness. Five of the six genes were differentially expressed. The five gene panel identified patients at low (7.1%) and high risk (66.7%) for non-SLN metastases.
A novel, non-SLN gene score based on differential expressed genes in a tumor-positive SLN can identify patients at high and low risk for non-SLN metastases.
University of Louisville School of Medicine Collaborative Matching Grant (HH), University of Louisville Clinical and Translational Science Pilot Grant Program Innovative Award (KMM), Melanoma Research Foundation Established Investigator Award (KMM). The University of Louisville Genomics Facility is supported by NCRR IDeA Awards INBRE-P20RR016481 and COBRE-P20RR018733, the James Graham Brown Foundation, and user fees.
Kelly M. McMasters reports that he is on the Board of Directors for Provectus Biopharmaceuticals and serves on the Scientific Advisory Board for Elucida Oncology.
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