Potential role for microRNA-16 (miR-16) and microRNA-93 (miR-93) in diagnosis and prediction of disease progression in mycosis fungoides in Egyptian patients.

Iman Mamdouh Talaat,Ahmed Taher El-Serafi,Naglaa Fathi Agamia,Maha Guimei,Rania ElSaied Abdelmaksoud,Ahmed Nugud,Arun Rishi

doi:10.1371/journal.pone.0224305

Iman Mamdouh Talaat, Ahmed Taher El-Serafi + Show 5 more

Open Access

https://doi.org/10.1371/journal.pone.0224305

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Abstract

Mycosis Fungoides (MF) is the most common type of cutaneous T-cell lymphomas. Early stage patients are treated with topical therapies and have normal life expectancy whereas patients with advanced disease encounter frequent relapses and have a five-year survival rate that does not exceed 15%. The aim of the present study was to characterize the expression of microRNA-16 (miR-16) and microRNA-93 (miR-93) in early and advanced cases of MF in relation to the clinicopathological parameters. Ten skin biopsies of early and advanced MF were investigated for the expression of miR-16 and miR-93 using RT-PCR. Immunohistochemical expression of apoptosis markers (BCL-2 and Survivin) were also investigated in the studied cases compared to normal skin and eczema biopsies. In the present study, BCL-2 and Survivin showed strong positive expression on neoplastic lymphocytes in all cases of MF regardless of their stage. We have also shown that miR-16 was significantly upregulated in advanced cases of MF compared to cases with early disease (p-value was less than 0.05). However, expression of miR-16 did not show any statistically significant correlation with age, gender, or expression of apoptotic markers. On the other hand, the expression of miR-93 showed significant downregulation in all lymphoma cases irrespective of their stage, compared to normal and eczema cases. Our results suggest that upregulation of miR-16 could be used to predict an aggressive course of the disease. We also suggest that miR-93 downregulation could serve as possible tool for establishing early diagnosis in early challenging cases. Our findings also provide consistent evidence that the anti-apoptotic molecules may play an important role in the pathogenesis of this type of cutaneous lymphomas and promote the idea that their inhibition could be an interesting novel therapeutic strategy in the treatment of MF.

Highlights

Cutaneous T-cell lymphomas (CTCLs) are rare types of non-Hodgkin lymphomas (NHLs) of the skin
The present study was conducted on 10 cases of mycosis fungoides (MF), 12 cases of eczema and 5 normal skin biopsies used as control (S1 Table)
According to the TNMB staging system, MF cases were divided into 2 groups; the first comprised 7 cases of ‘limited MF’; 3 cases of which were stage (IA) and 4 cases had stage (IB), the second group consisted of 3 cases with “advanced MF”; one case stage (IIA), and 2 cases staged as (IIB) “Fig 1”

Summary

Introduction

Cutaneous T-cell lymphomas (CTCLs) are rare types of non-Hodgkin lymphomas (NHLs) of the skin. The most common form of which is mycosis fungoides (MF). It accounts for around 55–60% of the new cases of CTCL diagnosed every year whereas Sezary syndrome (SS), its leukemic variant, accounts for 5% of the cases [1]. In MF, malignant T-cells are described singly or in clusters in the epidermis; a phenomenon known as “epidermotropism”. They form “Pautrier microabscesses” which are collections of malignant T-cells adherent to the processes of Langerhans cells. With progression of the disease, epidermotropism is gradually lost together with an increase in the number of malignant, and a decrease in non-malignant, infiltrating Tcells [2]

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