Acta Dermato-Venereologica 99-9CompleteContent | Page 15

809 INVESTIGATIVE REPORT Expression of CCR3 and CCR4 Suggests a Poor Prognosis in Mycosis Fungoides and Sézary Syndrome Yuki SHONO 1 , Hiraku SUGA 1 , Hiroaki KAMIJO 1 , Hikari FUJII 1 , Tomonori OKA 1 , Tomomitsu MIYAGAKI 1 , Naomi SHISHIDO- TAKAHASHI 2 , Makoto SUGAYA 2 and Shinichi SATO 1 1 Department of Dermatology, University of Tokyo Graduate School of Medicine, Tokyo, and 2 Department of Dermatology, International University of Health and Welfare, Chiba, Japan Tumor cells in cutaneous T-cell lymphoma express li- mited numbers of chemokine receptors. We investiga- ted the expression patterns of CXCR3, CCR3, CCR4 and CCR10 in mycosis fungoides, Sézary syndrome, lympho­ matoid papulosis and anaplastic large cell lymphoma in 121 skin biopsy samples. CXCR3 was expressed in 86% of mycosis fungoides cases but in no anaplastic large cell lymphoma cases. CCR3 was expressed in 73% of cases of CD30 + lymphoproliferative disorders such as lymphomatoid papulosis and anaplastic large cell lymphoma. Mycosis fungoides/Sézary syndrome pa- tients with high CCR3 or CCR4 expression had a poorer survival prognosis than mycosis fungoides/Sézary syndrome patients whose tumor cells did not express these receptors. CCR10 was expressed in 50% of my- cosis fungoides/Sézary syndrome cases and in 13% of cases with CD30 + lymphoproliferative disorders. These results suggest that differential patterns of CXCR3, CCR3, CCR4 and CCR10 expression are useful for the diagnosis of cutaneous T-cell lymphoma. Moreover, expression of CCR3 or CCR4 suggests a poor prognosis in mycosis fungoides/Sézary syndrome. Key words: CTCL; CXCR3; CCR3; CCR4; CCR10. Accepted Apr 30, 2019; E-published May 2, 2019 Acta Derm Venereol 2019; 99: 809–812. Corr: Hiraku Suga, M.D., Ph.D., Department of Dermatology, University of Tokyo Graduate School of Medicine, 7-3-1 Hongo, Bunkyo-ku, Tokyo 113-8655, Japan. E-mail: [email protected] T umor cells in cutaneous T cell lymphoma (CTCL) express limited numbers of chemokine receptors. CXCR3, a receptor for CXCL9, CXCL10 and CXCL11, is mainly expressed on Th1 cells and natural killer cells (1). CXCR3 has been reported to be expressed by epidermotropic T cells in mycosis fungoides (MF) (2). CCR3, which binds to CCL5, CCL7, CCL11, CCL13 and CCL26, is mainly expressed on eosinophils and subpopulations of Th2 cells (3), and CCR3 expression by atypical lymphoid cells has been related to anaplastic large cell lymphoma (ALCL) (4). CCR4 is a receptor for CCL17 and CCL22. CCL17 is expressed by dendritic cells and endothelial cells in lesional skin of patients with MF and Sézary syndrome (SS) (5), suggesting important roles of the CCL17-CCR4 interaction in the disease progression of MF/SS. CCL27 and CCL28, ligands for CCR10, are associated with the homing of SIGNIFICANCE Cutaneous T-cell lymphomas are a heterogeneous group of extranodal non-Hodgkin’s lymphomas that are charac- terized by a cutaneous infiltration of malignant monoclo- nal T lymphocytes. Tumor cells in cutaneous T-cell lymp- homa express limited numbers of chemokine receptors on their cell surface. We analyzed the expression patterns of CXCR3, CCR3, CCR4 and CCR10 in skin samples from patients with cutaneous T-cell lymphoma. In addition, we investigated the relationship between chemokine receptor expression and survival prognosis. Differential patterns of CXCR3, CCR3, CCR4 and CCR10 expression were useful for the diagnosis of cutaneous T cell lymphoma. Moreover, expression of CCR3 or CCR4 suggested a poor prognosis in cutaneous T-cell lymphoma. memory T lymphocytes to the skin (6). Keratinocytes express CCL27, which is accompanied by CCR10- positive tumor cell infiltration in lesional skin of patients with MF (7). In this study, we analyzed the patterns of CXCR3, CCR3, CCR4 and CCR10 expression in MF, SS, CD30 + lymphoproliferative disorders (LPDs) such as lymphomatoid papulosis (LyP) and ALCL and atopic dermatitis (AD). In addition, we investigated the rela­ tionship between chemokine receptor expression and survival prognosis in MF/SS. METHODS Clinical samples One hundred and twenty-one biopsy specimens were collected in our department from January 2008 to August 2018. Skin samples from cases of MF (n = 76), SS (n = 12), LyP (n = 10), ALCL (n = 5) and AD (n = 18) were used for immunohistochemistry. The samples enrolled in a previous report were also analyzed in this research (8). The medical ethical committee of the University of Tokyo approved all described studies, and the study was conducted ac­ cording to the principles of the Declaration of Helsinki.       Immunohistochemistry Fresh-frozen skin samples were used for immunohistochemistry. We used the following antibodies as primary antibodies: a mouse monoclonal antibody directed against CXCR3 (1C6, BD Biosciences Pharmingen, Heidelberg, Germany), a rabbit anti­ body against CCR3 (MBL International, Woburn, MA, USA), a mouse monoclonal antibody directed against CCR4 (1G1, BD Biosciences Pharmingen) and a goat antibody against CCR10 This is an open access article under the CC BY-NC license. www.medicaljournals.se/acta Journal Compilation © 2019 Acta Dermato-Venereologica.     doi: 10.2340/00015555-3207 Acta Derm Venereol 2019; 99: 809–812