Cyclin D1 overexpression in multiple myeloma - A morphologic, immunohistochemical, and in situ hybridization study of 71 paraffin-embedded bone marrow biopsy specimens

. Cyclin D1 expression was evaluated by immunohistochemical analysis and bi otin-labeled in situ hybridization (ISH) in a series of 71 decalcified, par affin-embedded bone marrow biopsy specimens from patients with multiple mye loma (MM). Cyclin D1 messenger RNA (mRNA) overexpression was detected by IS H in 23 (32%) of 71 cases, whereas cyclin D1 protein was identified by immu nohistochemical analysis in 17 (24%) of 71 specimens. All cases that were p ositive by immunohistochemical analysis also were positive by ISH. Statisti cally significant associations were found between cyclin D1 overexpression and grade of plasma cell differentiation and between cyclin D1 overexpressi on and extent of bone marrow infiltration. Our findings demonstrate the fol lowing: (1) ISH for cyclin D1 mRNA is a sensitive method for the evaluation of cycl in D1 overexpression in paraffin embedded bone marrow biopsy specimens with MM. (2) ISH is more sensitive than immunohistochemical analysis in the assessme nt of cyclin D1 expression. (3) Cyclin D1 overexpression in MM is correlated positively with higher his tologic grade and stage.