title: Loss of expression of 5-hydroxymethylcytosine in CD30-positive cutaneous lymphoproliferative disorders.
abstract: BACKGROUND
  The methylation of DNA at position 5 of cytosine, and the subsequent reduction in intracellular 5-hydroxymethylcytosine (5-hmC) levels, is a key epigenetic event in several cancers, including systemic lymphomas. However, no studies have analyzed this epigenetic marker in cutaneous lymphomas. Therefore, we aimed to analyze the expression of 5-hmC in cutaneous CD30-positive lymphoproliferative disorders and compare it with a control group composed of reactive infectious and inflammatory disorders with CD30-positive cells.
  
  
  METHODS
  Retrospective case series study with immunohistochemical analysis using anti-CD30 and anti-5-hmC antibodies in control (n = 19), lymphomatoid papulosis (LyP) (n = 27) and primary cutaneous anaplastic large cell lymphoma (ALCL) (n = 14) specimens.
  
  
  RESULTS
  Complete loss of 5-hmC nuclear staining by CD30+ cells was observed in 63% of LyP cases, 57% of ALCL cases and 0% of control cases.
  
  
  CONCLUSIONS
  The presence of 5-hmC+ and CD30+ lymphocytes was highly suggestive of a benign process. In contrast, loss of 5-hmC nuclear staining was highly suggestive of a lymphoproliferative disorder (ALCL or LyP). Under these circumstances, the use of 5-hmC staining can be a useful adjunctive tool for discriminating between neoplastic CD30+ lymphoproliferations and inflammatory/infectious simulators harboring reactive CD30+ cells.
authors.affiliation: Department of Dermatology, Harvard Medical School, Boston, MA, USA.
authors.forename: Aieska
authors.initials: A
authors.lastname: De Souza
authors.forename: Marianne
authors.initials: M
authors.lastname: Tinguely
authors.forename: Madeleine
authors.initials: M
authors.lastname: Pfaltz
authors.forename: Daniel R
authors.initials: DR
authors.lastname: Burghart
authors.forename: Werner
authors.initials: W
authors.lastname: Kempf
mesh_terms: D044503:5-Methylcytosine / Q000031:analogs & derivatives; D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D014408:Biomarkers, Tumor / Q000235:genetics / Q000378:metabolism; D016022:Case-Control Studies; D002648:Child; D003596:Cytosine / Q000031:analogs & derivatives* / Q000096:biosynthesis / Q000378:metabolism; D044127:Epigenesis, Genetic; D005260:Female; D006801:Humans; D007150:Immunohistochemistry / Q000379:methods; D017730:Ki-1 Antigen / Q000378:metabolism*; D054446:Lymphoma, Primary Cutaneous Anaplastic Large Cell / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D017731:Lymphomatoid Papulosis / Q000378:metabolism / Q000473:pathology; D008297:Male; D008875:Middle Aged; D012189:Retrospective Studies; D012878:Skin Neoplasms / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D055815:Young Adult
chemical_list: D014408:Biomarkers, Tumor; D017730:Ki-1 Antigen; C011865:5-hydroxymethylcytosine; D044503:5-Methylcytosine; D003596:Cytosine
keywords: 5-hydroxymethylcytosine; CD30 lymphoproliferative disorders; anaplastic large cell lymphoma; cutaneous lymphomas; epigenetic alterations