CKS1B nuclear expression is inversely correlated with p27Kip1 expression and is predictive of an adverse survival in patients with multiple myeloma.
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 is an adverse prognostic factor in multiple myeloma, but its relationship with CKS1B nuclear protein expression, is unclear. The aim of this study was to correlate nuclear CKS1B protein immunoreactivity, 1q21 amplification status, p27(Kip1) expression and survival in patients with newly-diagnosed multiple myeloma.


METHODS
Nuclear expression of CKS1B and p27(Kip1) was evaluated by immunohistochemistry in decalcified, paraffin-embedded bone marrow biopsies from 94 patients with newly diagnosed multiple myeloma. Clonal plasma cells of the bone marrow aspirates from the same cohort were examined for CKS1B gene status by interphase cytoplasmic fluorescence in situ hybridization.


RESULTS
Fluorescence in situ hybridization detected the 1q21 amplification in 36 (38%) of the 94 patients and immunohistochemistry showed CKS1B protein expression in 37 (39%). Thirty-two (86%) of the 36 amplified (1q21) cases expressed CKS1B and 31 (84%) of the 37 CKS1B immunore-active cases had amplified 1q21. 1q21 amplification and CKS1B protein expression were strongly correlated (P<0.0001). CKS1B protein expression was inversely correlated with p27(Kip1) immunostaining (P<0.0001) and was associated with a shorter overall survival (median 44.5 versus 89.3 months, P<0.0001).


CONCLUSIONS
Immunohistochemistry for CKS1B is a simple, rapid method that appears to predict 1q21 amplification and adverse outcome for risk stratification of patients with multiple myeloma.
Chang
Hong
H
Department of Laboratory Hematology, University Health Network, 200 Elizabeth Street, 11E-413 Toronto, ON, M5G 2C4. hong.chang@uhn.on.ca
Jiang
Nan
N
Jiang
Hua
H
Saha
Manujendra N
MN
Qi
Connie
C
Xu
Wei
W
Reece
Donna
D
D000328:Adult; D000368:Aged; D042846:CDC2-CDC28 Kinases / Q000032:analysis*; D050760:Cyclin-Dependent Kinase Inhibitor p27 / Q000032:analysis*; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D008297:Male; D008875:Middle Aged; D009101:Multiple Myeloma / Q000737:chemistry / Q000401:mortality*; D009687:Nuclear Proteins / Q000032:analysis; D011237:Predictive Value of Tests; D015996:Survival Rate
C093090:CKS1B protein, human; D009687:Nuclear Proteins; D050760:Cyclin-Dependent Kinase Inhibitor p27; D042846:CDC2-CDC28 Kinases