c-Jun expression and activation are restricted to CD30(+) lymphoproliferative disorders

Cellular Jun (c-Jun), a member of the JUN family, is an activator protein-l 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 lymphornatoid 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 ((Ser73)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 (Ser73)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.