Abstract
Background: Melanoma brain metastases are the main cause of specific death among patients with metastatic melanoma. The biology of melanoma brain metastases remains largely to be deciphered, as there have been only a few genomic studies on brain metastatic samples. In this study, melanoma metastatic lymph nodes were used with the aim to identify biomarkers associated with the occurrence of brain metastases. Methods: Fifty-one patients with melanoma lymph node metastasis and a median follow-up of 48 months were included in the development cohort. Transcriptomic data were obtained from these metastatic lymph nodes and patients who developed brain metastases and those who did not were compared. Recommendations for tumour marker prognostic studies (REMARK recommendations) were followed.Results: From transcriptomic data, we identified PROM2 which was significantly overexpressed in metastatic lymph nodes of patients who developed brain metastases compared to those who did not. Using immunohistochemistry with two different anti-PROM2 antibodies, a PROM2 score was developed for metastatic lymph nodes. Using a cut-off of 5, a PROM2 mean score ≥5 was significantly associated with an increased risk of brain metastases and an increased hazard risk of death by 4.These results were confirmed in an internal validation cohort of 50 additional patients with melanoma lymph node metastases.Conclusions: In this study, we identified PROM2 expression as a biomarker predictive of the occurrence of distant metastases, particularly brain metastases, among patients with stage III melanoma. Our findings open new perspectives to validate PROM2 as a useful biomarker for clinical trials in the adjuvant setting, and as a potential biotarget for the treatment of metastatic melanoma.
Nodal Melanocytic Nevi in Sentinel Lymph Nodes
