title: CD44 variant expression in cutaneous T-cell lymphoma.
abstract: Expression of the lymphocyte homing receptor CD44 and its splice variants have been linked to tumour dissemination and poor prognosis in non-Hodgkin's lymphoma. Specifically, the in vitro expression of variant exon V6 confers metastatic potential in rat pancreatic carcinoma cell lines. In this study, we investigated the expression of CD44 splice variants in cutaneous T-cell lymphomas, including patients with mycosis fungoides (MF), Sezary syndrome (SS), large-cell anaplastic lymphoma (LCAL) and HTLV1-associated cutaneous lymphoma. In addition, 4 involved lymph nodes from 2 patients with MF and 1 patient with SS were examined. Inflammatory dermatoses, lichen planus and psoriasis, and normal skin were also studied. Immunohistochemistry was performed using a panel of monoclonal antibodies, including those with specificity for CD44H (standard isoform) and variant exons V3, V6 and V8-9. Normal epidermal keratinocytes were consistently CD44H and CD44 V3, V6 and V8-9 positive. In all the different clinicopathological subtypes and stages of cutaneous T-cell lymphomas, including involved lymph nodes, tumour cells consistently expressed CD44H, but were CD44 V3 and V6 negative. CD44 V8-9 was expressed on a majority of tumour cells in 2/5 LCAL and on occasional tumour cells in 2/5 LCAL. Occasional V8-9 positive tumour cells were also identified in 6/13 MF, 1/4 SS and 3/4 HTLV1. In 2/3 lymph node samples from 2 patients with tumour-stage MF, CD44 V8-9 expression was found on a small percentage of atypical mononuclear cells. Scattered V8-9 positive dermal mononuclear cells were present in sections of lichen planus and psoriasis. We have found no evidence to suggest that the metastasis-associated CD44 variant exon (V6) is expressed in cutaneous T-cell lymphoma, or that CD44H expression is associated with an adverse prognostic group. It is not clear whether the strong expression of CD44 V8-9 in 2 patients with CD30 positive LCAL reflects activation status or metastatic potential.
authors.affiliation: Dept of Dermatology, Royal Free Hospital, London, UK.
authors.forename: C H
authors.initials: CH
authors.lastname: Orteu
authors.forename: W
authors.initials: W
authors.lastname: Li
authors.forename: M H
authors.initials: MH
authors.lastname: Allen
authors.forename: N P
authors.initials: NP
authors.lastname: Smith
authors.forename: J N
authors.initials: JN
authors.lastname: Barker
authors.forename: S J
authors.initials: SJ
authors.lastname: Whittaker
mesh_terms: D017398:Alternative Splicing; D006801:Humans; D018960:Hyaluronan Receptors / Q000235:genetics / Q000378:metabolism*; D007150:Immunohistochemistry; D008198:Lymph Nodes / Q000378:metabolism; D016410:Lymphoma, T-Cell, Cutaneous / Q000235:genetics / Q000378:metabolism*; D009182:Mycosis Fungoides / Q000378:metabolism; D012189:Retrospective Studies; D012751:Sezary Syndrome / Q000378:metabolism; D012878:Skin Neoplasms / Q000235:genetics / Q000378:metabolism*
chemical_list: D018960:Hyaluronan Receptors