Diagnostic microRNA profiling in cutaneous T-cell lymphoma (CTCL)

Ralfkiaer U, Hagedorn P H, Bangsgaard N, Løvendorf M B, Ahler C B, Svensson L, Kopp K L, Vennegaard M T, Lauenborg B, Zibert J R, Krejsgaard T, Bonefeld C M Søkilde R, Gjerdrum L M, Labuda T, Mathiesen A M, Grønbaek K, Wasik M A, Sokolowska-Wojdylo M, Queille-Roussel C, Gniadecki R, Ralfkiaer E, Geisler C, Litman T, Woetmann A, Glue C, Røpke M A, Skov L, Odum N

Blood 2011 Published online 24-08-2011

http://dx.doi.org/10.1182/blood-2011-06-358382

Cutaneous T-cell lymphomas (CTCL) are the most frequent primary skin lymphomas. Nevertheless, diagnosis of early disease has proven difficult due to a clinical and histological resemblance to benign inflammatory skin diseases. To address if microRNA (miRNA) profiling can discriminate CTCL from benign inflammation, we studied miRNA expression levels in 198 patients with CTCL, peripheral T-cell lymphoma (PTL), and benign skin diseases (psoriasis and dermatitis). Using microarrays we show that the most induced- (miR-326, miR-663b, miR-711) and repressed- (miR-203, miR-205) miRNAs distinguish CTCL from benign skin diseases with > 90% accuracy in a training set of 90 samples and a test set of 58 blinded samples. These miRNAs also distinguish malignant and benign lesions in an independent set of 50 patients with PTL and skin inflammation and in experimental human xenograft mouse models of psoriasis and CTCL. QRT-PCR analysis of 103 patients with CTCL and benign skin disorders validates differential expression of 4 out of the 5 miRNAs and confirms previous reports on miR-155 in CTCL. A qRT-PCR-based classifier consisting of miR-155, miR-203, and miR-205 distinguishes CTCL from benign disorders with high specificity, sensitivity, and a classification accuracy of 95% indicating that miRNAs have a high diagnostic potential in CTCL.