Premium
Low Drosha protein expression in cutaneous T‐cell lymphoma is associated with worse disease outcome
Author(s) -
Gambichler T.,
Salveridou K.,
Schmitz L.,
Käfferlein H.U.,
Brüning T.,
Stockfleth E.,
Sand M.,
Lang K.
Publication year - 2019
Publication title -
journal of the european academy of dermatology and venereology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.655
H-Index - 107
eISSN - 1468-3083
pISSN - 0926-9959
DOI - 10.1111/jdv.15652
Subject(s) - medicine , drosha , protein expression , outcome (game theory) , lymphoma , disease , oncology , cancer research , genetics , gene , rna , rna interference , biology , mathematics , mathematical economics
Background 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. Objectives We aimed to evaluate Drosha and Dicer protein expression in cutaneous T‐cell lymphoma (CTCL). Methods 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. Results 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). Conclusions 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.