title: TOX expression and role in CTCL.
abstract: BACKGROUND
  Cutaneous T-cell lymphomas (CTCL) are skin malignancies including mycosis fungoides (MF) and CD30(+) lymphoproliferative disorders (LPD). In early disease, CTCL can be difficult to diagnose, especially in MF for which there is no reliable diagnostic marker. MF/CTCL have increased expression of thymocyte selection-associated HMG box protein (TOX). Although TOX has been proposed to be a diagnostic marker for MF, further validation studies are needed. Moreover, it is unclear what drives TOX expression or its role in MF/CTCL.
  
  
  OBJECTIVE
  We hypothesize evaluation of TOX levels across a spectrum of CTCL, including MF precursor (large plaque parapsoriasis, LPP), will help elucidate the implications of altered TOX expression.
  
  
  METHODS
  TOX staining was performed in MF, CD30(+) LPD, LPP as well as benign inflammatory dermatoses (BID) and normal skin (NS). CTCL cell lines were utilized to evaluate the regulation of TOX.
  
  
  RESULTS
  Positive TOX expression was identified in 73.6% of MF cases and in 31.6% of BID/NS. TOX had a positive predictive value (PPV) for MF of 86.7% and a negative predictive value (NPV) of 48.1%. TOX expression in MF was detected more commonly in Black patients (P = 0.015) and less commonly in transformed MF (P = 0.045). LPP had positive TOX staining in 70.0%. In CTCL cells, GATA3 knockdown decreased TOX mRNA and protein expression. TOX expression also decreased in the presence of CTCL therapeutics.
  
  
  CONCLUSIONS
  Our data indicate that TOX is useful as a diagnostic marker in MF. Moreover, TOX expression was evident in LPP, indicating it may have a previously unappreciated role in the development of MF. Finally, our data suggest that GATA3 regulates TOX, revealing insight into TOX regulation.
authors.affiliation: Department of Hematology/Oncology, Levine Cancer Institute, Carolinas Medical Center, Charlotte, NC, USA.|Department of Medicine/Dermatology, Vanderbilt University Medical Center, Nashville, TN, USA.
authors.forename: L Y
authors.initials: LY
authors.lastname: McGirt
authors.affiliation: Department of Dermatology, Baylor College of Medicine, Houston, TX, USA.
authors.forename: C A
authors.initials: CA
authors.lastname: Degesys
authors.affiliation: Department of Medicine/Dermatology, Vanderbilt University Medical Center, Nashville, TN, USA.
authors.forename: V E
authors.initials: VE
authors.lastname: Johnson
authors.affiliation: Department of Medicine/Dermatology, Vanderbilt University Medical Center, Nashville, TN, USA.
authors.forename: J A
authors.initials: JA
authors.lastname: Zic
authors.affiliation: Department of Medicine/Dermatology, Vanderbilt University Medical Center, Nashville, TN, USA.
authors.forename: J P
authors.initials: JP
authors.lastname: Zwerner
authors.affiliation: Department of Pathology, Microbiology and Immunology, Vanderbilt University Medical Center, Nashville, TN, USA.|Department of Cancer Biology and the Sidney Kimmel Comprehensive Cancer Center Thomas Jefferson University Philadelphia, PA, USA.
authors.forename: C M
authors.initials: CM
authors.lastname: Eischen
mesh_terms: D050990:GATA3 Transcription Factor / Q000235:genetics; D006609:High Mobility Group Proteins / Q000235:genetics / Q000378:metabolism*; D006801:Humans; D016410:Lymphoma, T-Cell, Cutaneous / Q000150:complications / Q000378:metabolism* / Q000473:pathology; D009182:Mycosis Fungoides / Q000150:complications; D012333:RNA, Messenger / Q000235:genetics
chemical_list: D050990:GATA3 Transcription Factor; C494749:GATA3 protein, human; D006609:High Mobility Group Proteins; D012333:RNA, Messenger; C558851:TOX protein, human