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