CKS1B Overexpression and Genomic Analysis in Multiple Myeloma
N Jiang, J Jiang, W Xu, Y Trieu, C Qi, D Reece, H Chang. University Health Network, University of Toronto, Toronto, Canada
Background: CKS1B is a member of the highly conserved cyclin kinase subunit 1(CKS1) family that interacts with cyclin-dependent kinases and plays an important role in cell cycle progression. We and others have shown that CKS1B amplification located on chromosome 1q21.2, is associated with poor clinical outcome in patients with multiple myeloma (MM). However, whether CKS1B protein overexpression is detectable in myeloma cells and whether its expression affects the clinical outcome are not clear. Here, we explore the relationship between CKS1B gene amplification and its protein expression as well as its prognostic significance in a cohort of MM patients at our institution.
Design: The CKS1B expression was evaluated by immunohistochemistry (IHC) in decalcified, paraffin-embedded bone marrow biopsies from 103 MM patients. Clonal plasma cells of the bone marrow aspirates from the same cohort were examined for CKS1B gene status as well as other MM associated genetic changes by interphase cytoplasmic interphase FISH.The clinical data were collected by chart review.
Results: Of 103 patients, FISH detected CKS1B amplification deletion in 37 (36%) while IHC detected CKS1B overexpression in 41 (40%) of the cases. Of the 37 CKS1B amp. positive cases, 32 (86%) expressed CKS1B detected by IHC, whereas 32 (78%) of 41 IHC CKS1B positive cases had CKS1B amplification by FISH. CKS1B amplification and CKS1B overexpression were strongly correlated (P <0.0001). CKS1B overexpression was also associated with 13q and 17p(p53) deletions (P=0.013, P=0.009, respectively) but not with t(4;14) or t(11;14). Furthermore, patients with CKS1B overexpression had a significantly shorter overall survival than those without CKS1B overexpression (HR:4.67, 95%CI:1.74-12.5; P=0.0009).
Conclusions: Our results indicate that CKS1B is frequently overexpressed in MM cells and associated with poor survival in MM patients. The significant correlation between CKS1B protein expression and genomic gains suggests that the protein overexpression may be a result of gene amplification. CKS1B IHC may be used as a simple, rapid method to predict CKS1B amplification for risk stratification of MM.
Tuesday, March 23, 2010 9:30 AM
Poster Session III # 212, Tuesday Morning