Background
Methods
Patients and samples
Tissue microarray and immunohistochemistry
DNA extraction and mutation analysis of p53 and IDH1/2 genes
MGMT promoter methylation status
Fluorescence in situ hybridization (FISH)
Cell culture and immunoblot analysis
Immunofluorescence and confocal microscopy
Statistical analysis
Results
Expression of VRK1 and VRK2 serine-threonine kinases in human astrocytomas and correlations with tumor grade
VRK1 (nuclear staining) |
P value | |||
---|---|---|---|---|
Tumor | Negative | Positive | Total | |
Low-Grade
| 15 (62.5%) | 9 (37.5%) | 24 (100%) |
P = 0.146 |
High-Grade
| 36 (45.6%) | 43 (54.4%) | 79 (100%) |
VRK2 (cytoplasmic staining) |
P value | |||
---|---|---|---|---|
Tumor | Negative | Positive | Total | |
Low-Grade
| 14 (58.3%) | 10 (41.7%) | 24 (100%) |
P = 0.021 |
High-Grade
| 25 (32.1%) | 53 (67.9%) | 78 (100%) |
VRK protein correlations with proliferation markers p63 and ki67
p63 |
P value | |||
---|---|---|---|---|
Tumor | Negative | Positive | Total | |
Low-Grade
| 16 (66.7%) | 8 (33.3%) | 24 (100%) |
P < 0.001 |
High-Grade
| 20 (25.3%) | 59 (74.7%) | 79 (100%) |
ki-67 |
P value | ||||
---|---|---|---|---|---|
Tumor | 0-5% | 5-15% | >15% | Total | |
Low-Grade
| 21 (91.3%) | 2 (8.7%) | 0 (0.0%) | 23 (100%) |
P < 0.001 |
High-Grade
| 18 (28.6%) | 24 (38.1%) | 21 (33.3%) | 63 (100%) |
p63 | |||||
---|---|---|---|---|---|
Tumor | VRK1 (nuclear staining) | Negative | Positive | Total |
P value |
Low-Grade
|
Negative
| 13 (54.2%) | 2 (8.3%) | 24 (100%) | 0.007 |
Positive
| 3 (12.5%) | 6 (25.0%) | |||
High-Grade
|
Negative
| 15 (19.0%) | 21 (26.6%) | 79 (100%) | 0.002 |
Positive
| 5 (6.3%) | 38 (48.1%) |
ki-67 | ||||||
---|---|---|---|---|---|---|
Tumor | VRK2 (cytoplasmic staining) | 0-5% | 5-15% | >15% | Total |
P value |
Low-Grade
|
Negative
| 13 (56.6%) | 1 (4.3%) | 0 (0.0%) | 23 (100%) | 0.742 |
Positive
| 8 (34.8%) | 1 (4.3%) | 0 (0.0%) | |||
High-Grade
|
Negative
| 9 (14.5%) | 2 (3.2%) | 5 (8.1%) | 62 (100%) | 0.005 |
Positive
| 8 (12.9%) | 22 (35.5%) | 16 (25.8%) |
Mutation profile of astrocytomas
High VRK2 protein expression correlated with improved survival and is an independent marker of prognosis
Univariate analysis | Multivariate analysis | |||
---|---|---|---|---|
Parameter | HR (95% C.I.) |
P value | HR (95% C.I.) |
P value |
VRK2 expression
| 1.80 (1.07 – 3.02) | 0.025 | 2.10 (1.24 – 3.58) | 0.006 |
Age (<60 vs. ≥ 60)
| 1.94 (1.15 – 3.26) | 0.011 | 1.80 (1.06 – 3.05) | 0.031 |
Treatment (Chemo + RT vs. RT alone vs. no treatment)
| 1.96 (1.22 – 3.15) | 0.003 | 2.01 (1.22 – 3.30) | 0.006 |
Risk group | No. patients % | Hazard ratio (95% C.I.) | Median survival (months) (95% C.I.) |
P value | Survival rate | ||
---|---|---|---|---|---|---|---|
1-year | 2-year | 3-year | |||||
Low-risk | 28 (37.8%) | 1 | 15.7 (12.3 – 19.0) | <0.001 | 67.9% | 25.5% | 21.3% |
High-risk | 46 (62.2%) | 2.64 (1.53 – 4.55) | 9.8 (7.9 – 11.8) | 39.8% | 7.0% | 0.0% |