title: Cyclin kinase subunit 1B nuclear expression predicts an adverse outcome for patients with relapsed/refractory multiple myeloma treated with bortezomib.
abstract: Amplification of cyclin kinase subunit 1B gene on chromosome 1q21 resulting in overexpression of cyclin kinase subunit 1B has been associated with disease progression in multiple myeloma. Bortezomib is a proteasome inhibitor that induces apoptosis in various cancer cells and has been shown to be effective as a salvage therapy for relapsed/refractory multiple myeloma. Our group has recently reported the adverse effect of 1q21 gains in relapsed and refractory multiple myeloma treated with bortezomib. However, whether nuclear cyclin kinase subunit 1B protein expression correlates with 1q21 gains and has prognostic value in patients with multiple myeloma receiving bortezomib regimen remains unclear. We, therefore, evaluated the nuclear expression of cyclin kinase subunit 1B protein in patients with relapsed/refractory multiple myeloma undergoing bortezomib therapy by immunohistochemistry. The 1q21 amplification status of the same cohort was examined by interphase cytoplasmic immunoglobulin fluorescence in situ hybridization. Of 60 cases, 19 (32%) were positive for cyclin kinase subunit 1B nuclear expression by immunohistochemistry. Seventeen (89%) of the immunohistochemistry-positive cases had 1q21 gain detected by cytoplasmic immunoglobulin fluorescence in situ hybridization, and 17 (77%) of the 22 cases with 1q21 gain showed increased cyclin kinase subunit 1B protein expression. cyclin kinase subunit 1B expression and 1q21 gain were strongly correlated (P < .0001). There was no significant difference in response rate between patients with and without cyclin kinase subunit 1B nuclear expression. However, patients with cyclin kinase subunit 1B expression had a significantly shorter progression-free survival (1.9 versus 5.6 months; P < .0001) and overall survival (4.9 versus 22.4 months; P = .012) compared with those without cyclin kinase subunit 1B expression. Our results indicated that cyclin kinase subunit 1B nuclear expression detected by immunohistochemistry is an adverse prognostic factor for patients with multiple myeloma treated with bortezomib therapy.
authors: Department of Laboratory Medicine and Pathobiology, University of Toronto, Toronto, Canada.
authors: Mei-Hsi
authors: MH
authors: Chen
authors: Connie
authors: C
authors: Qi
authors: Donna
authors: D
authors: Reece
authors: Hong
authors: H
authors: Chang
mesh_terms: D000328:Adult; D000368:Aged; D000970:Antineoplastic Agents / Q000009:adverse effects* / Q000627:therapeutic use; D014408:Biomarkers, Tumor / Q000032:analysis / Q000235:genetics; D001897:Boronic Acids / Q000009:adverse effects* / Q000627:therapeutic use; D000069286:Bortezomib; D042846:CDC2-CDC28 Kinases / Q000096:biosynthesis* / Q000235:genetics; D002467:Cell Nucleus / Q000378:metabolism; D002878:Chromosomes, Human, Pair 1 / Q000235:genetics; D018572:Disease-Free Survival; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D017404:In Situ Hybridization, Fluorescence; D053208:Kaplan-Meier Estimate; D008297:Male; D008875:Middle Aged; D009101:Multiple Myeloma / Q000188:drug therapy / Q000235:genetics* / Q000378:metabolism*; D009364:Neoplasm Recurrence, Local / Q000188:drug therapy / Q000235:genetics* / Q000378:metabolism*; D011379:Prognosis; D016016:Proportional Hazards Models; D011719:Pyrazines / Q000009:adverse effects* / Q000627:therapeutic use
chemical_list: D000970:Antineoplastic Agents; D014408:Biomarkers, Tumor; D001897:Boronic Acids; C093090:CKS1B protein, human; D011719:Pyrazines; D000069286:Bortezomib; D042846:CDC2-CDC28 Kinases