Faculty Collaboration Database

c-Jun expression and activation are restricted to CD30+ lymphoproliferative disorders. Am J Surg Pathol 2007 Mar;31(3):447-53

Date

02/28/2007

Pubmed ID

17325487

DOI

10.1097/01.pas.0000213412.25935.e4

Scopus ID

2-s2.0-34247564713 (requires institutional sign-in at Scopus site)   32 Citations

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.

Author List

Drakos E, Leventaki V, Schlette EJ, Jones D, Lin P, Medeiros LJ, Rassidakis GZ

MESH terms used to index this publication - Major topics in bold

Biomarkers, Tumor
Cell Count
Cell Line, Tumor
Cell Nucleus
Hodgkin Disease
Humans
Ki-1 Antigen
Lymphoma, Non-Hodgkin
Lymphomatoid Papulosis
Phosphorylation
Proto-Oncogene Proteins c-jun
Serine
Tissue Array Analysis
Transcriptional Activation