CDKN2/p16 predicts survival in oligodendrogliomas: comparison with astrocytomas.
Cyclin-dependent kinase 4 inhibitor (CDKN2/p16) is a cell cycle regulatory protein that has been demonstrated to be inactivated by mutations, deletions or transcriptional silencing during pathogenesis of a variety of human malignancies. We studied the correlation of CDKN2/p16 expression with cell proliferation activity and patient survival in 42 oligodendrogliomas and 36 astrocytomas. CDKN2/p16 expression was frequently decreased in grade II and anaplastic oligodendrogliomas (17/42) where lack of CDKN2/p16 protein predicted poor survival (p = 0.0045). In astrocytomas low CDKN2/p16 expression was associated with high histologic malignancy grade (p = 0.002): CDKN2/p16 protein level was decreased in 9 out of 10 glioblastomas, in 5 out of 9 anaplastic astrocytomas, in 3 out of 10 grade II astrocytomas and in none of pilocytic astocytomas (0/7). Low CDKN2/p16 expression was also associated with high cell proliferation activity (MIB-1 immunocytochemistry: p = 0.004; mitotic index: p = 0.007) and poor patient survival (p = 0.025) in astrocytomas. Low CDKN2/p16 mRNA expression had the same topographic distribution as nuclear CDKN2/p16 immunoreactivity proving for reliability of the immunocytochemical findings. Our results are in agreement with earlier studies demonstrating CDKN2/p16 inactivation during tumorigenesis of astrocytic tumors. Furthermore, our findings suggest that loss of CDKN2/p16 expression may also play an important role in the progression of oligodendrogliomas. According to our findings CDKN2/p16 immunocytochemistry could be used as a tool to identify those oligodendrogliomas and low grade astrocytomas that are likely to progress and have poor outcome, and thus would need more aggressive therapy.
Miettinen
H
H
Department of Anatomy, Tampere University Medical School, Tampere University Hospital, Finland.
Kononen
J
J
Sallinen
P
P
Alho
H
H
Helen
P
P
Helin
H
H
Kalimo
H
H
Paljärvi
L
L
Isola
J
J
Haapasalo
H
H
D000293:Adolescent; D000328:Adult; D000368:Aged; D001254:Astrocytoma / Q000235:genetics / Q000401:mortality / Q000473:pathology* / Q000601:surgery; D001932:Brain Neoplasms / Q000235:genetics / Q000401:mortality / Q000473:pathology* / Q000601:surgery; D002455:Cell Division; D002648:Child; D002675:Child, Preschool; D019941:Cyclin-Dependent Kinase Inhibitor p16 / Q000032:analysis* / Q000235:genetics; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D007150:Immunohistochemistry; D017403:In Situ Hybridization; D007700:Kinetics; D008297:Male; D008875:Middle Aged; D009837:Oligodendroglioma / Q000235:genetics / Q000401:mortality / Q000473:pathology* / Q000601:surgery; D011237:Predictive Value of Tests; D011379:Prognosis; D012189:Retrospective Studies; D015996:Survival Rate; D013997:Time Factors
D019941:Cyclin-Dependent Kinase Inhibitor p16