Unilesional mycosis fungoides is associated with increased expression of microRNA‐17~92, and Th1 skewing

Summary

Background

The molecular basis of unilesional mycosis fungoides (MF), characterized by a solitary lesion which is clinicopathologically indistinguishable from multifocal patch/plaque MF (early MF), is unknown.

Objectives

To investigate the microRNA (miR) profile in unilesional MF distinguishing it from early MF.

Methods

Biopsy samples of unilesional MF and early MF were evaluated with the Affymetrix microRNA array, with further comparison to inflammatory dermatosis, using quantitative polymerase chain reaction. NanoString technology was applied to analyze the gene expression of T‐helper (Th)1 immune markers and immunohistochemistry was used to evaluate C‐X‐C motif cytokine receptor 3 (CXCR3) and GATA binding protein 3 (GATA3), markers for Th1 and Th2 cells, respectively.

Results

Unilesional MF had a significantly higher level of expression of all members of the miR‐17~92 cluster than early MF. Specifically, compared to early MF, unilesional MF was characterized by a higher miR‐17 level and inflammatory dermatoses, downregulation of the expression of phosphatase and tensin homolog (Pten) and cAMP response element binding protein 1 (CREB1), known targets of miR 17~92 members, higher gene expressions of interluekin‐2 (IL‐2), and interferon gamma (IFN‐ɣ), and statistically lower average percentage of GATA3+ dermal cells (6·7% vs 42·3%, respectively). High immunoreactivity of CXCR3 was noted in both unilesional and early MF.

Conclusions

Unilesional MF exhibits a microRNA profile distinct from conventional early MF, with a higher level of miR‐17~92 members along with a Th1 skewing. These findings suggest a robust reactive T‐cell immune response in unilesional MF and might account for the localized nature of this disease.

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