Expression of the Voltage-Gated Potassium Channel Kv1.3 in Lesional Skin from Patients with Cutaneous T-Cell Lymphoma and Benign Dermatitis
| Autor: | Pieter Spee, Terkild B. Buus, Andreas Hald, Maria Gluud, Thorbjørn Krejsgaard, Claudia Nastasi, Andreas Willerslev-Olsen, Niels Ødum, Lise Mette Rahbek Gjerdrum, Edda Blümel, Jens Eriksen, Pia Rude Nielsen, Anders Woetmann, Anneline Nansen, Tengpeng Hu, Michael Bzorek |
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| Rok vydání: | 2019 |
| Předmět: |
Adult
Male Pathology medicine.medical_specialty Skin Neoplasms Adolescent Biopsy Dermatitis Dermatology Malignancy complex mixtures Flow cytometry Young Adult 030207 dermatology & venereal diseases 03 medical and health sciences 0302 clinical medicine immune system diseases Cell Line Tumor medicine Humans natural sciences Child Aged Skin Aged 80 and over Mycosis fungoides Kv1.3 Potassium Channel biology medicine.diagnostic_test urogenital system business.industry Cutaneous T-cell lymphoma Middle Aged medicine.disease Immunohistochemistry KCNA3 Lymphoma T-Cell Cutaneous Lymphoma Staining nervous system 030220 oncology & carcinogenesis biology.protein Female business |
| Zdroj: | Dermatology. 236:123-132 |
| ISSN: | 1421-9832 1018-8665 |
| DOI: | 10.1159/000502137 |
| Popis: | Background: The voltage-gated potassium channel Kv1.3 (KCNA3) is expressed by effector memory T cells (TEM) and plays an important role in their activation and proliferation. Mycosis fungoides (MF), the most common subtype of cutaneous T-cell lymphoma (CTCL), was recently proposed to be a malignancy of skin-resident TEM. However, the expression of Kv1.3 in CTCL has not been investigated. Objectives: This study aims to examine the expression of Kv1.3 in situ and in vitro in CTCL. Methods: The expression of Kv1.3 was examined by immunohistochemistry in skin lesions from 38 patients with MF, 4 patients with Sézary syndrome (SS), and 27 patients with benign dermatosis. In 4 malignant T-cell lines of CTCL (Myla2059, PB2B, SeAx, and Mac2a) and a non-malignant T-cell line (MyLa1850), the expression of Kv1.3 was determined by flow cytometry. The proliferation of those cell lines treated with various concentrations of Kv1.3 inhibitor ShK was measured by 3H-thymdine incorporation. Results: Half of the MF patients (19/38) displayed partial Kv1.3 expression including 1 patient with moderate Kv1.3 positivity, while the other half (19/38) exhibited Kv1.3 negativity. An almost identical distribution was observed in patients with benign conditions, that is, 44.4% (12/27) were partially positive for Kv1.3 including 1 patient with moderate Kv1.3 positivity, while 55.6% (15/27) were Kv1.3 negative. In contrast, 3 in 4 SS patients displayed partial Kv1.3 positivity including 2 patients with weak staining and 1 with moderate staining, while 1 in 4 SS patients was Kv1.3 negative. In addition, all malignant T-cell lines, and a non-malignant T-cell line, displayed low Kv1.3 surface expression with a similar pattern. Whereas 2 cell lines (PB2B and Mac2a) were sensitive to Kv1.3 blockade, the other 2 (Myla2059 and SeAx) were completely resistant. Conclusions: We provide the first evidence of a heterogeneous Kv1.3 expression in situ in CTCL lesions. |
| Databáze: | OpenAIRE |
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