Aberrant CCND1 copies and cyclin D1 mRNA expression do not result in the production of functional cyclin D1 protein in anaplastic large cell lymphoma

Abstract

Scattered reports in the literature have shown that Cyclin D1 mRNA and protein may be expressed in anaplastic large cell lymphoma (ALCL). ALCLs are characterized by the presence of ALK translocations. Aberrant Cyclin D1 expression seems to promote proliferation in other types of lymphoma, while a growth promoting CCND1/TACSD1(TROP2) fusion product has also been described in tumors. Herein, we investigated 44 ALCL cases for chromosome 11 and CCND1 status (by FISH), cyclin D1 mRNA expression (by in situ hybridization and RT-PCR) and Cyclin D1 protein (by immunohistochemistry with two different monoclonal antibodies), as well as for the expression of Trop-2/GA733-1 (by immunohistochemistry). Polysomy of CCND1 (11q13) and chromosome 11 was found in 15/38 evaluated cases (39.5%). This change was specific for CD30+ neoplastic cells, as shown by double fluorescent staining. Neoplastic cells in the majority of ALCL expressed cyclin D1 mRNA (29/41 [70.7%]), in association with the presence of ALK translocations (p=0.024) and systemic, rather than cutaneous disease (p=0.021). Remarkably, however, Cyclin D1 protein was not detected in neoplastic cells (0/44 cases), neither were these found positive for Trop-2. In conclusion, aberrant copies of CCND1 / chromosome 11 may be observed in ALCL, probably as a consequence of the reported ploidy changes in these tumors. ALCL may often express cyclin D1 mRNA, which, however, does not result in the production of functional Cyclin D1 protein or Trop-2, suggesting that these proteins do not play a role in the pathogenesis of ALCL.