OBJECTIVE: HDAC inhibitors (HDI) are anti-neoplastic drugs with preliminary successful clinical applications in Hodgkin's lymphoma (HL). Systematic investigations of HDAC expression in HL, based on histology and immunohistochemistry are yet rare. RESEARCH DESIGN/ METHODS: We investigated the expression of HDAC1, 2 and 3 in 283 HL on tissue microarrays. MAIN OUTCOME MEASURES: Expression of HDAC isoforms was scored in Hodgkin and Reed-Sternberg cells (HRSC) and background infiltrate and compared with freedom of treatment failure (FTF) in 118 cases, for which all data was available. RESULTS: All analyzable HL expressed the HDAC isoforms 2 (n = 194) and 3 (n = 207) in over 50%, mostly 100%, of HRSC and almost all background lymphocytes. HDAC1 was expressed in 169 of 179 analyzable HL in a mean of 82% and in 172 out of 179 analyzable cases in a mean of 83% of infiltrating lymphocytes. HDAC1 of below 75% in HRSC correlated with worse FTF with 16 out of 32 events, compared with 16 out of 82 in cases with over 75% HDAC1-expressing HRSC. CONCLUSION: HDAC isoforms 1, 2 and 3 are highly expressed in HL. In addition, decreased HDAC1 expression is accompanied by worse outcome in HL.
OBJECTIVE: HDAC inhibitors (HDI) are anti-neoplastic drugs with preliminary successful clinical applications in Hodgkin's lymphoma (HL). Systematic investigations of HDAC expression in HL, based on histology and immunohistochemistry are yet rare. RESEARCH DESIGN/ METHODS: We investigated the expression of HDAC1, 2 and 3 in 283 HL on tissue microarrays. MAIN OUTCOME MEASURES: Expression of HDAC isoforms was scored in Hodgkin and Reed-Sternberg cells (HRSC) and background infiltrate and compared with freedom of treatment failure (FTF) in 118 cases, for which all data was available. RESULTS: All analyzable HL expressed the HDAC isoforms 2 (n = 194) and 3 (n = 207) in over 50%, mostly 100%, of HRSC and almost all background lymphocytes. HDAC1 was expressed in 169 of 179 analyzable HL in a mean of 82% and in 172 out of 179 analyzable cases in a mean of 83% of infiltrating lymphocytes. HDAC1 of below 75% in HRSC correlated with worse FTF with 16 out of 32 events, compared with 16 out of 82 in cases with over 75% HDAC1-expressing HRSC. CONCLUSION: HDAC isoforms 1, 2 and 3 are highly expressed in HL. In addition, decreased HDAC1 expression is accompanied by worse outcome in HL.
Authors: Sophie S B Giguère; Amanda J Guise; Pierre M Jean Beltran; Preeti M Joshi; Todd M Greco; Olivia L Quach; Jeffery Kong; Ileana M Cristea Journal: Mol Cell Proteomics Date: 2015-12-09 Impact factor: 5.911