title: c-Jun expression and activation are restricted to CD30+ lymphoproliferative disorders.
abstract: Cellular Jun (c-Jun), a member of the JUN family, is an activator protein-1 transcription factor involved in cell differentiation, proliferation, and apoptosis that can be activated by phosphorylation at serine-73 and -63 residues. Using tissue microarrays and immunohistochemistry, we investigated c-Jun expression and serine-73 phosphorylation in 112 CD30 lymphomas and 232 CD30 lymphomas of B- or T-cell lineage, and 24 cases of lymphomatoid papulosis. c-Jun was expressed exclusively by CD30 lymphoproliferative disorders including 41/41 (100%) classical Hodgkin lymphoma (cHL), 20/23 (87%) anaplastic lymphoma kinase (ALK)+ anaplastic large cell lymphoma (ALCL), 18/26 (69%) ALK- ALCL, 5/9 (56%) primary cutaneous ALCL, 4/11 (36%) CD30 diffuse large B-cell lymphoma (DLBCL), and 11/24 (46%) cases of lymphomatoid papulosis. The percentage of c-Jun-positive tumor cells was highest in cHL and ALCL (P=0.002). In contrast, all CD30 lymphomas, including nodular lymphocyte predominant HL and CD30 non-Hodgkin lymphomas of B- or T-cell lineage were negative for c-Jun. Serine-73 phosphorylated c-Jun (p-c-Jun), the activated form of c-Jun, was expressed more frequently and at a higher level in cHL and ALK+ ALCL than other CD30 tumors. The percentage of p-c-Jun-positive tumor cells correlated significantly with the percentage of total c-Jun-positive cells (P<0.0001), suggesting that activated c-Jun positively regulates total c-Jun levels in CD30 lymphomas through a well-established positive feedback loop. We conclude that CD30 lymphomas are characterized by common patterns of c-Jun expression and activation suggesting a potential role of c-Jun in the pathogenesis of these tumors.
authors.affiliation: Department of Hematopathology, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA.
authors.forename: Elias
authors.initials: E
authors.lastname: Drakos
authors.forename: Vasiliki
authors.initials: V
authors.lastname: Leventaki
authors.forename: Ellen J
authors.initials: EJ
authors.lastname: Schlette
authors.forename: Dan
authors.initials: D
authors.lastname: Jones
authors.forename: Pei
authors.initials: P
authors.lastname: Lin
authors.forename: L Jeffrey
authors.initials: LJ
authors.lastname: Medeiros
authors.forename: George Z
authors.initials: GZ
authors.lastname: Rassidakis
mesh_terms: D014408:Biomarkers, Tumor / Q000096:biosynthesis; D002452:Cell Count; D045744:Cell Line, Tumor; D002467:Cell Nucleus / Q000378:metabolism / Q000473:pathology; D006689:Hodgkin Disease / Q000378:metabolism / Q000473:pathology*; D006801:Humans; D017730:Ki-1 Antigen / Q000378:metabolism*; D008228:Lymphoma, Non-Hodgkin / Q000378:metabolism / Q000473:pathology*; D017731:Lymphomatoid Papulosis / Q000378:metabolism / Q000473:pathology*; D010766:Phosphorylation; D016755:Proto-Oncogene Proteins c-jun / Q000378:metabolism*; D012694:Serine / Q000378:metabolism; D046888:Tissue Array Analysis; D015533:Transcriptional Activation
chemical_list: D014408:Biomarkers, Tumor; D017730:Ki-1 Antigen; D016755:Proto-Oncogene Proteins c-jun; D012694:Serine