Changes in histone acetylation, microvessel density by CD31⁺ dermal vessels, thrombospondin-1 (TSP-1) expression, and phospho–STAT-3 (p-STAT-3) localization following 4 weeks of vorinostat treatment. (A) Histone acetylation (Ac H4K8) of keratinocytes and lymphocytes was intense at baseline. (B) After vorinostat treatment, AC H4K8 was less intense because most of the lymphocytes were not present. (C-D) CD31⁺ dermal vessels were reduced following 4 weeks of therapy in all patients, including responders. (E-F) The antiangiogenic protein TSP-1 was up-regulated following vorinostat treatment, with increased staining in the epidermis and dermal infiltrates. (G-H) p-STAT-3 staining shifted from the nuclei to cytoplasm of keratinocytes and lymphocytes following vorinostat treatment.