Immunohistochemical Analysis of Cyclin D1 and p53 in Multiple Myeloma: Relationship to Proliferative Activity and Prognostic Significance

Abstract

Conflicting data are reported on the clinical significance of cyclin D1 deregulation in multiple myeloma. The aim of this study was to evaluate the incidence and prognostic significance of cyclin D1 expression and p53 mutations in multiple myeloma, as well as the relationship of their expression with selected clinical data, histological features, and proliferative activity of myeloma cells. We analyzed bone marrow biopsy specimens obtained from 59 patients with newly diagnosed multiple myeloma. Expression of cyclin D1 and p53 was analyzed using standard immunohistochemical method of B5-fixed and routinely processed paraffin-embedded bone marrow specimens. Cyclin D1 was overexpressed in 14/59 (27%) and p53 in 5/59 (8.5%) specimens. There was no significant correlation between cyclin D1 overexpression and age, gender, clinical stage (Durie-Salmon classification), extent of osteolytic lesions, type of monoclonal protein, hemoglobin concentration, platelet count, serum concentration of creatinine, calcium, C-reactive protein, and beta2-microglobulin. No association was observed between the expression of cyclin D1 and the extent of bone marrow infiltration, histological grade, proliferative activity index (measured with Ki-67 immunoreactivity) and response to therapy. No significant difference was observed regarding overall survival between cyclin D1 positive and cyclin D1 negative patients (29 vs 36 mo, p = 0.76). Results of this study did not revealed prognostic significance of cyclin D1 overexpression in multiple myeloma. Mutations of p53 gene are rare events in myeloma, suggesting their limited role in the pathogenesis of the disease.

Genomic aberrations and immunohistochemical markers as prognostic indicators in multiple myeloma

“…As a result of this mutation, the half-life of the mutated p53 protein is increased compared with that of the wild-type, enabling detection by IHC 60 – 62. The incidence of p53 protein expression in myeloma, as detected by IHC, has been reported to be between 8 and 39%, but its relationship with p53 gene deletion status has only recently been investigated 41 52 63 64. In a study of 105 newly diagnosed MM patients, we demonstrated a strong correlation between nuclear p53 expression and the presence of a hemizygous p53 deletion as detected by FISH 10.…”

Cyclin D1 expression in multiple myeloma by immunohistochemistry: Case series of 14 patients and literature review

“…[18] However, a correlation between cyclin D1 expression, clinical parameters, histologic stage and the degree of differentiation of neoplastic plasma cells (histologic grading) has been reported only in a small series of patients. [1317192021222324]…”

Immunohistochemical Analysis Identifies Two Cyclin D1+ Subsets of Plasma Cell Myeloma, Each Associated With Favorable Survival

“…In contrast, a previous study of cyclin D1 immunohistochemical analysis in 59 cases of myeloma showed no differences in outcome between positive and negative cases. 23 This discrepancy might be due to differences in the antibodies used and the smaller percentage of cyclin D1+ cases identified in the earlier analysis. The present study confirmed the finding of the RT-PCR-based study of Soverini et al 9 that increased cyclin D1 expression is a favorable prognostic factor in plasma cell myeloma.…”

“…19,[22][23][24] Although t(11;14)(q13;q32)-positive cases typically are positive for cyclin D1 protein by immunohistochemical analysis, only a subset of cases with detectable cyclin D1 staining is associated with t(11;14)(q13;q32). 19,24,25 Previous studies, however, have been limited by the nature of most available cyclin D1 antibodies, which generally are associated with high background and variable staining intensities in most laboratories.…”