Improving Melanoma Classification by Integrating Genetic and Morphologic Features

作者：Amaya Virós, Jane Fridlyand, Jürgen M. Bauer, Konstantin Lasithiotakis, Claus Garbe, Daniel Pinkel, Boris C. Bastian · 发表于：PLoS Medicine · 年份：2008 · DOI：10.1371/journal.pmed.0050120 · 被引用次数：384 · 研究领域：Cutaneous Melanoma Detection and Management、Melanoma and MAPK Pathways、Infrared Thermography in Medicine

BACKGROUND: In melanoma, morphology-based classification systems have not been able to provide relevant information for selecting treatments for patients whose tumors have metastasized. The recent identification of causative genetic alterations has revealed mutations in signaling pathways that offer targets for therapy. Identifying morphologic surrogates that can identify patients whose tumors express such alterations (or functionally equivalent alterations) would be clinically useful for therapy stratification and for retrospective analysis of clinical trial data. METHODOLOGY/PRINCIPAL FINDINGS: We defined and assessed a panel of histomorphologic measures and correlated them with the mutation status of the oncogenes BRAF and NRAS in a cohort of 302 archival tissues of primary cutaneous melanomas from an academic comprehensive cancer center. Melanomas with BRAF mutations showed distinct morphological features such as increased upward migration and nest formation of intraepidermal melanocytes, thickening of the involved epidermis, and sharper demarcation to the surrounding skin; and they had larger, rounder, and more pigmented tumor cells (all p-values below 0.0001). By contrast, melanomas with NRAS mutations could not be distinguished based on these morphological features. Using simple combinations of features, BRAF mutation status could be predicted with up to 90.8% accuracy in the entire cohort as well as within the categories of the current World Health Organization (WHO) ...