title: TOX expression in cutaneous T-cell lymphomas: an adjunctive diagnostic marker that is not tumour specific and not restricted to the CD4(+)  CD8(-) phenotype.
abstract: BACKGROUND
  TOX (thymocyte selection-associated high-mobility group box) was shown to be aberrantly expressed in mycosis fungoides (MF) and Sézary syndrome (SS) and is suggested to have additional diagnostic value. However, data on expression in other types of cutaneous T-cell lymphoma (CTCL) are scarce and it is unknown whether TOX is expressed only by MF with a CD4(+)  CD8(-) phenotype.
  
  
  OBJECTIVE
  To investigate TOX expression in various types of CTCL with different T-cell phenotypes.
  
  
  METHODS
  Immunohistochemical expression of TOX was evaluated on 153 skin biopsies of 132 patients with CTCL and 60 patients with benign inflammatory dermatoses (BIDs).
  
  
  RESULTS
  TOX was expressed by > 50% of the neoplastic T cells in 49 of 59 patients (83%) with MF and in 19 of 22 patients (86%) with SS. The TOX(+) cases of MF included 34 of 35 cases (97%) with a CD4(+)  CD8(-) phenotype, but also five of eight cases (63%) with a CD4(-)  CD8(+) phenotype and 10 of 16 cases (63%) with a CD4(-)  CD8(-) phenotype. TOX expression in other types of CTCL was common but showed variable intensity. Although only one of 60 patients (2%) with a BID expressed TOX in > 50% of the skin-infiltrating T cells, some caution is warranted, as the majority of BIDs had TOX(+) T cells varying between 11% and 50%.
  
  
  CONCLUSIONS
  TOX expression is not tumour specific, is not restricted to CTCL with a CD4(+)  CD8(-) phenotype, and, on its own, is insufficient for diagnosis of CTCL. However, it may have an adjunctive diagnostic role in conjunction with other clinical and histological data.
authors.affiliation: Department of Pathology, Leiden University Medical Centre, Leiden, the Netherlands.
authors.forename: A M R
authors.initials: AM
authors.lastname: Schrader
authors.affiliation: Department of Pathology, Leiden University Medical Centre, Leiden, the Netherlands.
authors.forename: P M
authors.initials: PM
authors.lastname: Jansen
authors.affiliation: Department of Dermatology, Leiden University Medical Centre, Leiden, the Netherlands.
authors.forename: R
authors.initials: R
authors.lastname: Willemze
mesh_terms: D014408:Biomarkers, Tumor / Q000378:metabolism*; D015496:CD4-Positive T-Lymphocytes / Q000378:metabolism; D018414:CD8-Positive T-Lymphocytes / Q000378:metabolism; D003937:Diagnosis, Differential; D006609:High Mobility Group Proteins / Q000378:metabolism*; D006801:Humans; D016410:Lymphoma, T-Cell, Cutaneous / Q000175:diagnosis*; D009182:Mycosis Fungoides / Q000175:diagnosis; D010641:Phenotype; D012751:Sezary Syndrome / Q000175:diagnosis
chemical_list: D014408:Biomarkers, Tumor; D006609:High Mobility Group Proteins; C558851:TOX protein, human