High Expression of Sonic Hedgehog Pathway Mediators in Mycosis Fungoides Skin Samples: A Retrospective Analysis

Mycosis Fungoides (MF) is characterized by clonal proliferation of CD4+ lymphocytes within the skin. Recent studies report dysregulation of the Sonic Hedgehog (Shh) pathway expressed in neoplastic cells of primary T-cell lymphomas. We aim to assess the expression of Ptch-1, Bcl-2, Smo, and Gli-1, mediators in Shh pathway, in cutaneous biopsies of MF. Biopsies were retrospectively collected at the University of Miami Hospital between 01/2018 and 12/2021, including samples of clinically proven MF, healthy controls (HC), and basal cell carcinoma (BCC) as positive control. Immunohistochemistry was performed using commercially available antibodies, and two-way ANOVA and Tukey’s multiple comparisons test were used to assess statistical significance. 35 biopsy samples, including 19 MF, 12 HC, and 4 BCC were analyzed, and revealed significantly higher expression of Smo, Gli-1, and Bcl-2 in MF biopsies compared to HC, as quantified by the number of positive cells/mm2.Due to the elevated expression of Shh mediators found in MF samples, larger studies are necessary to assess the potential role of the Shh pathway in MF pathogenesis.

The data contains our supplemental images for Bcl-2 and Ptch-1 immunohistochemistry staining of cutaneous biopsies of MF, HC, and basal cell carcinoma.

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Supplemental Figure 1. 1a) Bcl-2 expression was significantly elevated compared to healthy controls. The results were heterogenous among samples, ranging from no expression to as high as 1,500 cells/mm2 1b) Expression was primarily localized to the stratum basale layer of the epidermis in MF samples, leaving the dermis relatively spared. Very few cells stained positive for Bcl-2 among BCC or HC samples, with no statistical significance.

Supplemental Fig 2. 2a) Ptch-1 expression in MF biopsies was not statistically significant compared to controls. 2b) Ptch-1 was localized sparingly within the papillary dermis and epidermis in MF biopsies. Ptch-1 expression was seen predominantly within the basaloid cells of the basal cell carcinoma (positive controls).