CD164 and FCRL3 Are Highly Expressed on CD4+CD26 − T Cells in Sézary Syndrome Patients

Abstract

Sézary syndrome (SS) cells express cell surface molecules also found on normal activated CD4 T cells. In an effort to find a more specific surface marker for malignant SS cells, a microarray analysis of gene expression was performed. Results showed significantly increased levels of mRNA for CD164, a sialomucin found on human CD34+ hematopoietic stem cells, and FCRL3, a molecule present on a subset of human natural T regulatory cells. Both markers were increased in CD4 T cells from SS patients compared to healthy donors. Flow cytometry studies confirmed the increased expression of CD164 and FCRL3 primarily on CD4+CD26− T cells of SS patients. Importantly, a statistically significant correlation was found between an elevated percentage of CD4+CD164+ T cells and an elevated percentage of CD4+CD26− T cells in all tested SS patients but not in patients with Mycosis Fungoides and atopic dermatitis or healthy donors. FCRL3 expression was significantly increased only in high tumor burden patients. CD4+CD164+ cells displayed cerebriform morphology and their loss correlated with clinical improvement in treated patients. Our results suggest that CD164 can serve as a marker for diagnosis and for monitoring progression of CTCL/SS and that FCRL3 expression correlates with a high circulating tumor burden.

Overexpression of CD164 in oral cavity squamous cell carcinoma predicts a favourable prognosis

“…The role of CD164 is ambiguous and remains unclear in the aforementioned studies; the results of the present study support the hypothesis that CD164 inhibits cell proliferation (17)(18)(19)(20)(21)(22)27,28).…”

“…Thus, they suggested that increased CD164 expression is involved in ovarian cancer progression through the stromal cell-derived factor 1a/C-X-C chemokine receptor type 4 axis, which promotes tumourigenicity. Wysocka et al (20) evaluated 6 patients with Sézary syndrome and 3 healthy donors, and identified that CD164 could be used to diagnose and monitor cases of the disease. This potential diagnostic role was also observed by Guenova et al (19) who investigated CD164 expression in malignant T-cells from 8 patients with…”

“…CD164 serves important roles in regulating proliferation, adhesion and differentiation in progenitor and hematopoietic stem cells as well as negative regulation of haematopoiesis (15). However, few cancer-associated studies have examined this protein and, to the best of our knowledge, no studies have considered it in the context of head and neck cancer (16)(17)(18)(19)(20)(21)(22). Therefore, the present study aimed to investigate the association of CD164 expression with clinicopathological parameters and prognosis in patients with OSCC.…”

Flow Cytometric Identification of Immunophenotypically Aberrant T-Cell Clusters on Skin Shave Biopsy Specimens From Patients With Mycosis Fungoides

“…© American Society for Clinical Pathology from patients with either advanced stage MF or the more aggressive variant of CTCL, Sézary syndrome (SS). 9,[17][18][19][20] Indeed, identification of CD4+ T cells lacking CD26 and/or CD7 by FC is a widely accepted strategy to quantify peripheral blood tumor cells in both MF and SS, with profound implications for staging and prognosis. 5,9,21 16 precluding the utilization of CD26 negativity as a sole marker to distinguish neoplastic from background reactive T cells in biopsy specimens.…”

CD164 promotes tumor progression and predicts the poor prognosis of bladder cancer

“…As a multifunctional protein, CD164 acted as a surface marker of hematopoietic stem cells, a CXCR4 promoter activity‐enhancing transcription factor, and a stem cell‐specific marker inducer 9, 10, 11. High expression of CD164 was found in several malignant diseases and was associated with clinical outcomes of patients 13, 23, 28, 29, 30, 31. In lung cancer, the positive associations were significantly existed between CD164 expression and tumor size, tumor cell grading, and lymph node involvement 14.…”