Acta Dermato-Venereologica 99-12CompleteContent | Page 22

1148 INVESTIGATIVE REPORT The MicroRNA Expression Profile Differs Between Erythrodermic Mycosis Fungoides and Sézary Syndrome Anne Hald RITTIG 1 , Lise Maria LINDAHL 1 , Claus JOHANSEN 1 , Pamela CELIS 2 , Niels ØDUM 3 , Lars IVERSEN 1 and Thomas LITMAN 3 Department of Dermatology, Aarhus University Hospital, 2 Department of Molecular Medicine, Aarhus University, Aarhus, and 3 Leo Foundation Skin Immunology Research Center; Department of Immunology and Microbiology, University of Copenhagen, Copenhagen, Denmark 1 It is difficult to distinguish erythrodermic mycosis fungoides from Sézary syndrome due to their similar clinical and histological features. The main purpose of this study was to investigate whether microRNA ex- pression profiles in lesional skin could discriminate pa- tients with erythrodermic mycosis fungoides from those with Sézary syndrome. A further aim was to assess whether the microRNA expression profiles in erythro- dermic mycosis fungoides skin was more comparable to microRNA expression profiles of Sézary syndrome or early-stage mycosis fungoides. RNA was extracted from diagnostic skin biopsies, followed by quantita- tive reverse transcription polymerase chain reaction analysis of 383 microRNAs. Twenty-seven microRNAs were significantly differentially expressed between erythro­dermic mycosis fungoides and Sézary syndro- me. More­over, erythrodermic mycosis fungoides sho- wed microRNA features overlapping with Sézary syn- drome and early-stage mycosis fungoides, although hierarchical cluster analysis co-clustered erythro- dermic mycosis fungoides with early-stage mycosis fungoides rather than with Sézary syndrome. These findings underscore that erythrodermic mycosis fungoides and Sézary syndrome are different diseases. Key words: mycosis fungoides, Sézary syndrome, cutaneous T- cell lymphoma, microRNA. Accepted Aug 26, 2019; E-published Aug 27, 2019 Acta Derm Venereol 2019; 99: 1148–1153. Corr: Anne Hald Rittig, Department of Dermatology, Aarhus University Hospital, Palle Juul-Jensens Boulevard 99, E201, DK-8200 Aarhus N, Den- mark. E-mail: [email protected] C utaneous T-cell lymphoma (CTCL) is a group of rare heterogeneous lymphoproliferative disorders prima- rily confined to the skin. The most prevalent clinical form of CTCL is mycosis fungoides (MF) (1, 2). Early-stage MF comprises patch and plaque skin lesions, whereas advanced stages involve skin tumours and erythrodermic MF (eMF) (3, 4). eMF and the more aggressive leukae- mic variant, Sézary syndrome (SS), are characterized by chronic erythroderma with ≥ 80% skin involvement (4). eMF and SS are difficult to distinguish because of their similar clinical features, with erythroderma and lymph­ adenopathy combined with symptoms such as pruritus, skin burning, and chills (5). However, eMF sometimes progresses through patch- and/or plaque-stage disease doi: 10.2340/00015555-3306 Acta Derm Venereol 2019; 99: 1148–1153 SIGNIFICANCE Erythrodermic mycosis fungoides and Sézary syndrome share clinical and histological features, making it difficult to distinguish these diseases. It has been discussed previous- ly whether erythrodermic mycosis fungoides and Sézary syndrome are different stages of the same disease. How­ ever, differences in treatment and prognoses indicate that the diseases should be considered separately. MicroRNAs are small sequences of RNA, which have the potential to discriminate clinically similar diseases. This study showed that 27 microRNAs discriminated erythrodermic mycosis fungoides from Sézary syndrome. These data support the perception of erythrodermic mycosis fungoides and Sézary syndrome as different diseases. and has various levels of blood involvement, whereas SS usually presents with erythroderma and significant blood involvement (6, 7). Controversies still exist regarding whether MF and SS are distinct diseases or different manifestations of a single disease (8, 9), which has led to substantial discussions about the distinction between eMF and SS (6, 9, 10). Discrimination between SS and eMF is essential due to differences in treatment recom- mendations and prognosis (7, 11, 12). MicroRNAs (miRNAs) may have the potential to discriminate between SS and eMF. miRNAs are short non-coding RNA molecules that regulate gene expres- sion by modulating translation of messenger RNA (13). Thus, miRNAs are involved in important biological functions, and altered regulation of miRNAs plays a key role in cancer development, progression and metastasis (14). Many miRNAs are differentially expressed in CTCL compared with normal skin (15–17). They have been proposed to discriminate CTCL from benign skin diseases as a diagnostic marker (18–20), and a prognostic 3-miRNA classifier was developed recently for patients diagnosed with early-stage MF (21). Moreover, single miRNAs (e.g. miR-155) may have essential regulatory functions in CTCL (22, 23), and a drug targeting miR- 155, cobomarsen, was developed recently and tested in a clinical trial with promising outcomes (24). This study examined the miRNA expression profiles of diagnostic lesional skin biopsies from early-stage MF, eMF, and SS, with the aim of: (i) examining whether a distinct miRNA expression profile can discriminate eMF from SS; and (ii) addressing whether the miRNA This is an open access article under the CC BY-NC license. www.medicaljournals.se/acta Journal Compilation © 2019 Acta Dermato-Venereologica.