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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