Date Published: June 12, 2018
Publisher: Public Library of Science
Author(s): Rebeca Manso, Nerea Martínez-Magunacelaya, Itziar Eraña-Tomás, Verónica Monsalvez, José L. Rodríguez-Peralto, Pablo-L Ortiz-Romero, Carlos Santonja, Ion Cristóbal, Miguel A. Piris, Socorro M. Rodríguez-Pinilla, Klaus Roemer.
Differentiating early mycosis fungoides (MF) from inflammatory dermatitis is a challenge. We compare the differential expression profile of early-stage MF samples and benign inflammatory dermatoses using microRNA (miRNA) arrays. 114 miRNAs were found to be dysregulated between these entities. The seven most differentially expressed miRNAs between these two conditions were further analyzed using RT-PCR in two series comprising 38 samples of early MFs and 18 samples of inflammatory dermatitis. A series of 51 paraffin-embedded samples belonging to paired stages of 16 MF patients was also analyzed. MiRNAs 26a, 222, 181a and 146a were differentially expressed between tumoral and inflammatory conditions. Two of these miRNAs (miRNA-181a and miRNA-146a) were significantly deregulated between early and advanced MF stages. Bioinformatic analysis showed FOXP3 expression to be regulated by these miRNAs. Immunohistochemistry revealed the level of FOXP3 expression to be lower in tumoral MFs than in plaque lesions in paraffin-embedded tissue. A functional study confirmed that both miRNAs diminished FOXP3 expression when overexpressed in CTCL cells. The data presented here suggest that the analysis of a restricted number of miRNAs (26a, 222, 181a and 146a) could be sufficient to differentiate tumoral from reactive conditions. Moreover, these miRNAs seem to be involved in MF progression.
Mycosis fungoides (MF) is the most frequent cutaneous T-cell lymphoma (CTCL) type, accounting for almost 50% of all CTCLs [1, 2] MF patients initially show cutaneous infiltration by neoplastic cells (patch, plaque and tumor), and the disease eventually progresses to include lymph node, peripheral blood or systemic involvement in late stages. Clinical and pathological diagnosis of early MF stages (patch and plaque) is difficult because of the morphological similarity to inflammatory dermatitis and the low proportion of tumoral cells .
This paper reports two significant strands. First, we identified a subset of miRNAs that are differentially expressed in inflammatory cutaneous conditions and early MF stages, and which could therefore be used to recognize MF. Second, we found that a more restricted set of miRNAs appears to be involved in MF progression, at least partially as a consequence of their capacity to regulate the T-cell phenotype.