High cyclin E/low p27Kip1 expression is associated with poor prognosis in astrocytomas.
Cyclin E and p27Kip1 are co-regulators of the G1- to S-phase transition and closely related to tumor behavior. The purpose of this study was to examine expression of cyclin E and p27Kip1 in astrocytomas and to evaluate the relationships between expression of these cell-cycle regulators and prognosis of patients with astrocytoma. Tissue samples from 130 astrocytomas (WHO grade 1 n = 5, grade 2 n = 23, grade 3 n = 64, grade 4 n = 38) were examined immunohistochemically for cyclin E and p27Kip1 expression. Patient charts were reviewed for clinical presentation, and survival was followed. The cyclin E labeling index (LI) tended to increase with tumor grade (Kruskal-Wallis, P = 0.0104). For patients with primary astrocytomas, the 50% survival times for the low cyclin E LI (< 5%) group and the high cyclin E LI (> or = 5%) group were 53.7 months and 19.8 months. In combined analysis of cyclin E and p27Kip1 expression, the low cyclin E/high p27Kip1 LI (> or = 50%) group had the best survival (50% survival time: 103.2 months), the low cyclin E/low p27Kip1 LI (> or = 50%) and the high cyclin E/high p27Kip1 LI groups moderate survival (24.1 and 27.5 months), and the high cyclin E/low p27Kip1 LI group the worst survival (13.1 months). Multivariate analysis identified the combined factor, high cyclin E/low p27Kip1, as a novel independent prognostic factor for survival time (P = 0.0037, relative risk = 2.4). This study suggested that combined analysis of cyclin E and p27Kip1 expression was considered to be potentially useful in predicting the prognosis of patients with astrocytoma.
Tamiya
T
T
Department of Neurological Surgery, Okayama University Medical School, 2-5-1 Shikata-cho, Okayama 700-8558, Japan. ttamiya@med.okayama-u.ac.jp
Mizumatsu
S
S
Ono
Y
Y
Abe
T
T
Matsumoto
K
K
Furuta
T
T
Ohmoto
T
T
D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D001254:Astrocytoma / Q000737:chemistry* / Q000235:genetics / Q000401:mortality / Q000473:pathology; D001932:Brain Neoplasms / Q000737:chemistry* / Q000235:genetics / Q000401:mortality / Q000473:pathology; D018797:Cell Cycle Proteins / Q000032:analysis* / Q000235:genetics; D002648:Child; D002675:Child, Preschool; D019927:Cyclin E / Q000032:analysis* / Q000235:genetics; D050760:Cyclin-Dependent Kinase Inhibitor p27; D005260:Female; D005500:Follow-Up Studies; D020869:Gene Expression Profiling; D015972:Gene Expression Regulation, Neoplastic; D005909:Glioblastoma / Q000737:chemistry / Q000235:genetics / Q000401:mortality / Q000473:pathology; D006801:Humans; D007223:Infant; D007231:Infant, Newborn; D007564:Japan / Q000453:epidemiology; D015993:Life Tables; D008297:Male; D008875:Middle Aged; D009363:Neoplasm Proteins / Q000032:analysis* / Q000235:genetics; D009419:Nerve Tissue Proteins / Q000032:analysis* / Q000235:genetics; D011379:Prognosis; D016019:Survival Analysis; D025521:Tumor Suppressor Proteins / Q000032:analysis* / Q000235:genetics
D018797:Cell Cycle Proteins; D019927:Cyclin E; D009363:Neoplasm Proteins; D009419:Nerve Tissue Proteins; D025521:Tumor Suppressor Proteins; D050760:Cyclin-Dependent Kinase Inhibitor p27