Low Drosha protein expression in cutaneous T-cell lymphoma is associated with worse disease outcome.

Abstract

Dysregulation of microRNAs (miRNAs) key regulators may contribute to the pathogenesis of malignancies. miRNA machinery genes such Dicer and Drosha have been reported to be biomarkers in different cancer types. We aimed to evaluate Drosha and Dicer protein expression in cutaneous T-cell lymphoma (CTCL). We performed Drosha and Dicer immunohistochemistry in 45 patients with mycosis fungoides and subtypes. Drosha and Dicer expression scores were correlated with clinical parameters including disease-specific death (DSD), stage of disease and different laboratory data. Uni- and multivariate statistics were performed. On univariate analysis, elevated serum LDH and low Drosha expression were significantly associated with advanced stage (P=0.032 and 0.0062, respectively) and lymphoma-specific death (LSD; P=0.017 and P=0.005, respectively). Moreover, elevated circulating CD4+/CD26- lymphocytes were significantly associated with advanced stage (P=0.032) and DSD (P=0.0098). On multivariate analysis, low Drosha expression remained in the logistic regression model as significant independent predictor for advanced disease stages [P=0.013; odds ratio: 5 (confidence interval) CI 1.3-19.3]. Moreover, low Drosha expression (P=0.026) and elevated LDH (P=0.025) remained as significant independent predictors for DSD with odds ratios of 13.5 (CI 1.3-134.4 and 8.7 CI 1.3-57.2, respectively). Low Drosha expression is an independent predictor for advanced stage as well as LSD in CTCL patients indicating a tumour suppressor gene function of Drosha in this disorder.