CKS1B Nuclear Expression Predicts an Adverse Outcome for Multiple Myeloma Patients Treated with Bortezomib.
Mei-Hsi Chen, Connie Qi, Hong Chang. University Health Network, Toronto, Canada
Background: Cyclin kinase subunit 1B (CKS1B) regulates cell cycle by activating cyclin-dependent kinases. Overexpression of CKS1B and amplification of CKS1B gene on chromosome 1q21 have been associated with disease progression in multiple myeloma (MM), an incurable hematological malignancy characterized by clonal proliferation of plasma cells. Bortezomib is a proteasome inhibitor that induces apoptosis in various cancer cells and has shown to be effective as a salvage therapy for relapsed/refractory MM. Our group has previously reported the adverse effect of 1q21 gain on the clinical outcome in MM patients treated with bortezomib. However, whether nuclear CKS1B protein expression correlates with 1q21 gains and has prognostic value in MM patients receiving bortezomib regimen remains unclear.
Design: Nuclear expression of CKS1B protein was evaluated by immunohistochemistry (IHC) on decalcified, paraffin-embedded bone marrow biopsies from 60 relapsed/refractory MM patients undergoing bortezomib therapy. The 1q21 gain/amplification status of the same cohort was examined by interphase fluorescence in situ hybridization (cIg-FISH).
Results: Nineteen (32%) of 60 cases were positive for CKS1B nuclear expression by IHC. Seventeen (89%) of the IHC positive cases had 1q21 gain detected by cIg-FISH, and 17 (77%) of the 22 cases with 1q21 gain showed increased CKS1B protein expression. CKS1B expression and 1q21 gain were strongly correlated (p<0.001). Thirty (50%) patients responded to the treatment with a medium progression-free survival (PFS) of 5.0 months and overall survival (OS) of 11.2 months. There was no significant difference in response rate between patients with or without CKS1B nuclear expression. However, Patients with CKS1B expression had a significantly shorter PFS (2.1 vs. 6.7 months, p<0.001) and overall survivals (7.7 vs. 14.4 months, p=0.009) compared with those without CKS1B expressions.
Conclusions: Our results indicated that CKS1B nuclear expression is an adverse prognostic factor for MM patients treated with bortezomib therapy. CKS1B IHC, a simple and rapid method, may be used as a surrogate marker of 1q21 gains for stratification of MM patients receiving bortezomib therapy.
Tuesday, March 1, 2011 9:30 AM
Poster Session III # 244, Tuesday Morning