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CKS1B nuclear expression is inversely correlated with p27Kip1 expression and is predictive of an adverse survival in
Hong Chang1, Nan Jiang, Hua Jiang
1Department of Laboratory Hematology, University Health Network, 200 Elizabeth Street, 11E-413 Toronto, ON, M5G 2C4. hong.chang@uhn.on.ca
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.
Design And 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.
Insights
Cyclin kinase subunit 1B (CKS1B) amplification and nuclear protein expression are linked in multiple myeloma, indicating a poor prognosis. Immunohistochemistry for CKS1B can predict adverse outcomes and aid in patient risk stratification.
Area of Science:
- Oncology
- Molecular Biology
- Genetics
Background:
- CKS1B, a cell cycle regulator, is amplified at chromosome 1q21 in multiple myeloma.
- 1q21 amplification is an adverse prognostic factor, but its correlation with CKS1B protein expression is unknown.
- Understanding this relationship is crucial for multiple myeloma patient stratification.
Purpose of the Study:
- To correlate nuclear CKS1B protein expression with 1q21 amplification status.
- To investigate the relationship between CKS1B expression, p27(Kip1) levels, and patient survival.
- To evaluate CKS1B immunohistochemistry as a predictive tool for multiple myeloma.
Main Methods:
- Immunohistochemistry was used to assess CKS1B and p27(Kip1) nuclear expression in 94 newly diagnosed multiple myeloma bone marrow biopsies.
- Interphase fluorescence in situ hybridization (FISH) analyzed CKS1B gene status (1q21 amplification) in clonal plasma cells.
- Correlation analyses were performed between CKS1B expression, 1q21 amplification, p27(Kip1), and overall survival.
Main Results:
- 1q21 amplification was detected in 38% of patients; CKS1B protein expression was observed in 39%.
- A strong correlation existed between 1q21 amplification and CKS1B protein expression (P<0.0001).
- CKS1B expression inversely correlated with p27(Kip1) (P<0.0001) and was associated with significantly shorter overall survival (44.5 vs. 89.3 months, P<0.0001).
Conclusions:
- CKS1B nuclear protein expression strongly correlates with 1q21 amplification in multiple myeloma.
- Immunohistochemistry for CKS1B is a rapid and effective method to predict 1q21 amplification.
- CKS1B expression serves as a valuable biomarker for adverse outcome prediction and risk stratification in multiple myeloma.
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