Expression of chemokines and chemokine receptors in cutaneous CD30+ lymphoproliferative disorders.
BACKGROUND
Little is known about the mechanisms involved in skin-specific homing in CD30+ cutaneous lymphoproliferative disorders (CLPD). Chemokine/chemokine receptor interactions have been implicated in the homing of lymphoma cells to various tissue sites.


OBJECTIVE
To investigate tissue samples from patients with CD30+ CLPD for the expression of the chemokine receptors CXCR3, CCR4 and CCR3 and their ligands MIG, TARC and RANTES.


METHODS
Tissue samples from patients with primary cutaneous anaplastic large cell lymphoma (PCALCL, n=12) and lymphomatoid papulosis (LyP, n=13) were studied by immunohistochemistry on paraffin-embedded sections. Immunohistochemical analysis was also performed for CD20 (for B cells), CD45RO and CD3 (for T cells), CD30 and ALK-1. A portion of each skin specimen was stored at -80 degrees C and later examined using monoclonal antibodies against CD2, CD3, CD4, CD5, CD8, CD15, CD19, CD20 and CD30.


RESULTS
CD30+ atypical lymphoid cells were frequently seen in PCALCL, and to a variable degree in LyP. In both disorders there were scattered CD3+ and CD45RO+ atypical lymphoid cells, but CD2, CD5, CD15, CD19, CD20 and ALK-1 showed negative reactivity. In addition, CD4+, but not CD8+, atypical lymphoid cells were occasionally seen in both disorders. CCR3 was expressed by atypical lymphoid cells in 10 of 12 (83%) cases of PCALCL, but in only five of 13 (38%) cases of LyP. CXCR3 was expressed in 11 of 13 (85%) cases of LyP, but in only one of 12 (8%) cases of PCALCL. CCR4 was expressed in 11 of 12 (92%) cases of PCALCL, but in only two of 13 (15%) cases of LyP. RANTES was strongly expressed by lymphoma cells in PCALCL (11 of 12: 92%), but was weak or sporadic in LyP (seven of 13: 54%). TARC showed weak or sporadic reactivity in both LyP and PCALCL, and MIG did not show a distinctive expression pattern in either disorder.


CONCLUSIONS
We speculate that CCR3 is associated with the autocrine function in PCALCL, as evidenced by CCR3 coexpression with its ligand RANTES. We also found that LyP cells expressed CXCR3, which might support their migration towards the CXCR3 ligand MIG, which is expressed in stromal cells of the skin.
Yamaguchi
T
T
Department of Pathology, School of Medicine, Fukuoka University, 7-45-1 Nanakuma, Jonan-ku, Fukuoka 814-0180, Japan. yamaguchi@minf.med.fukuoka-u.ac.jp
Ohshima
K
K
Karube
K
K
Kawano
R
R
Nakayama
J
J
Suzumiya
J
J
Kikuchi
M
M
D000293:Adolescent; D000328:Adult; D018946:Chemokine CCL5 / Q000378:metabolism; D054370:Chemokine CXCL9; D018925:Chemokines / Q000378:metabolism*; D019743:Chemokines, CXC / Q000378:metabolism; D002648:Child; D005260:Female; D006801:Humans; D017730:Ki-1 Antigen / Q000032:analysis; D008024:Ligands; D017728:Lymphoma, Large-Cell, Anaplastic / Q000276:immunology* / Q000473:pathology; D017731:Lymphomatoid Papulosis / Q000276:immunology* / Q000473:pathology; D008297:Male; D008875:Middle Aged; D009363:Neoplasm Proteins / Q000378:metabolism; D054397:Receptors, CCR3; D054367:Receptors, CXCR3; D019707:Receptors, Chemokine / Q000378:metabolism*; D012878:Skin Neoplasms / Q000276:immunology* / Q000473:pathology
C515350:CCR3 protein, human; C080810:CXCL9 protein, human; C515187:CXCR3 protein, human; D018946:Chemokine CCL5; D054370:Chemokine CXCL9; D018925:Chemokines; D019743:Chemokines, CXC; D017730:Ki-1 Antigen; D008024:Ligands; D009363:Neoplasm Proteins; D054397:Receptors, CCR3; D054367:Receptors, CXCR3; D019707:Receptors, Chemokine