Differential expression of cell-cycle regulatory proteins defines distinct classes of follicular lymphoma

Inactivation of the CDKN2A Tumor-Suppressor Gene by Deletion or Methylation Is Common at Diagnosis in Follicular Lymphoma and Associated with Poor Clinical Outcome

“…by IHC is associated with inferior OS in follicular lymphoma (22). We now observe that the prognostic impact of CDKN2A deletion/methylation status persists when p16…”

“…We showed recently that abundant expression of p16 INK4a , as determined by conventional IHC, was associated with clinical and pathologic evidence of more aggressive disease, including reduced OS, elevated serum LDH, grade 3 histology, and the presence of an associated component of DLBCL (22). The association between abundant p16…”

“…No statistically significant associations were noted between CDKN2A status and sex, FLIPI score, ECOG stage, LDH, performance status, number of involved nodal sites, the presence of B symptoms, histologic grade, the presence of a component of DLBCL, or the proliferation index (Table 3). We previously determined the prevalence in these cases of cells expressing the cell-cycle regulatory proteins p53, pRb, or cyclin D3 by IHC; no statistically significant associations were evident between these markers and CDKN2A status (22). Finally, because differences in treatment can contribute to differences in survival, it is noteworthy that we observed no statistically significant associations between CDKN2A status and receipt of either first-line treatment with chemotherapy plus rituximab or maintenance rituximab (Table 4).…”

“…Laser-capture microdissection and DNA extraction Eight-millimeter sections of FFPE biopsy samples were mounted on uncharged glass slides and immunostained with an anti-CD20 antibody (Epitomics) using an automated immunostaining device as previously described to identify lymphoma cells (22). In cases where lymphoma cells congregated within lymphoid follicles, as usually occurred, entire follicles were collected by laser-capture microdissection (LCM); tissue from 3 to 10 lymphoid follicles, or an equivalent quantity of neoplastic tissue, was collected per case ( Supplementary Fig.…”

Regulation of the G1/S Transition in Adult Liver: Expression and Activation of the Cyclin Dependent Kinase Cdk1 in Differentiated Hepatocytes is Controlled by Extracellular Signals and is Crucial for Commitment to DNA Replication

“…Indeed, both Cdk4 and Cdk6 can associate to Cyclins D1, D2 and D3 to form active complexes phosphorylating pRb (Bates et al, 1994;Matsushime et al, 1994). However, these six complexes are rarely found expressed in a single cell type and are rather expressed differentially in normal or transformed cells (Alhejaily et al, 2011;Fiaschi-Taesch et al, 2010). In addition, while in cells actively proliferating Cdk1 is expressed constantly throughout the cell cycle, in cells proliferating after a cell cycle arrest in G0, such as lymphocytes and hepatocytes, Cdk1 is barely detectable in G1 but appears at the G1/S transition (Furukawa et al, 1990;Loyer et al, 1994).…”