SATB1 Defines a Subtype of Cutaneous CD30+ Lymphoproliferative Disorders Associated with a T-Helper 17 Cytokine Profile

Cutaneous CD30+ lymphoproliferative disorders (LPDs), including lymphomatoid papulosis (LyP) and primary cutaneous anaplastic large-cell lymphoma, comprise the second most common group of cutaneous T-cell lymphomas. Previously, we reported that special SATB1, a thymocyte-specific chromatin organizer, was overexpressed and promoted malignant T-cell proliferation in a portion of CD30+ LPDs. Here, we investigated the expression pattern of SATB1 in CD30+ LPDs with a large cohort of patient samples, and examined the potential of SATB1 as a molecular marker to classify CD30+ LPDs with differential clinicopathological behaviors. SATB1 expression was identified in the CD30+ anaplastic T cells in 11 of 12 (91.7%) lymphomatoid papulosis and 16 of 42 (38.1%) primary cutaneous anaplastic large-cell lymphoma cases. SATB1+ cases showed T-helper 17 polarization, together with more prominent epidermal hyperplasia and granulocytic infiltration. SATB1+ lesions responded better to combined treatment of methotrexate and interferon. SATB1 activated the expression of T-helper 17 cytokines while repressing T-helper 1-related genes. The heterogeneity in SATB1 expression across CD30+ LPDs was associated with the extent of promoter DNA methylation. Hence, SATB1 expression defines a subtype of CD30+ LPDs with characteristic pathobiology and prognosis. These data provide valuable insights into the heterogeneity of cutaneous T-cell malignancies, which may lead to individualized therapy in the future.