Miettinen H, Kononen J, Sallinen P, Alho H, Helen P, Helin H, Kalimo H, Paljärvi L, Isola J, Haapasalo H
Department of Anatomy, Tampere University Medical School, Tampere University Hospital, Finland.
J Neurooncol. 1999 Feb;41(3):205-11. doi: 10.1023/a:1006185220369.
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.
细胞周期蛋白依赖性激酶4抑制剂（CDKN2/p16）是一种细胞周期调节蛋白，已证实在多种人类恶性肿瘤的发病过程中，它会因突变、缺失或转录沉默而失活。我们研究了42例少突胶质细胞瘤和36例星形细胞瘤中CDKN2/p16表达与细胞增殖活性及患者生存率的相关性。在II级和间变性少突胶质细胞瘤（17/42）中，CDKN2/p16表达经常降低，其中缺乏CDKN2/p16蛋白预示着生存率低（p = 0.0045）。在星形细胞瘤中，CDKN2/p16低表达与高组织学恶性程度相关（p = 0.002）：10例胶质母细胞瘤中有9例、9例间变性星形细胞瘤中有5例、10例II级星形细胞瘤中有3例CDKN2/p16蛋白水平降低，而毛细胞型星形细胞瘤中无一例降低（0/7）。在星形细胞瘤中，CDKN2/p16低表达还与高细胞增殖活性相关（MIB-1免疫细胞化学：p = 0.004；有丝分裂指数：p = 0.007）以及患者生存率低（p = 0.025）。CDKN2/p16 mRNA低表达与核CDKN2/p16免疫反应性具有相同的拓扑分布，证明了免疫细胞化学结果的可靠性。我们的结果与早期研究一致，这些研究表明在星形细胞肿瘤的肿瘤发生过程中CDKN2/p16失活。此外，我们的研究结果表明，CDKN2/p16表达缺失在少突胶质细胞瘤的进展中可能也起重要作用。根据我们的研究结果，CDKN2/p16免疫细胞化学可作为一种工具，用于识别那些可能进展且预后不良的少突胶质细胞瘤和低级别星形细胞瘤，因此可能需要更积极的治疗。
