Immunohistochemical analysis of p161INK4A, p14ARF, p18INK4c, p21CIP1, p27KIP1 and p73 expression in 271 meningiomas correlation with tumor grade and clinical outcome
Immunohistochemical analysis of p161INK4A, p14ARF, p18INK4c, p21CIP1, p27KIP1 and p73 expression in 271 meningiomas correlation with tumor grade and clinical outcome
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DOI：
10.1002/ijc.11013
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发表时间：
2003-05-10
影响因子：
6.4
通讯作者：
Golanov, A
中科院分区：
文献类型：
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作者：
Korshunov, A;Shishkina, L;Golanov, A
常规病理检查不能明确预测脑膜瘤的临床病程，因为即使组织学上良性的肿瘤也可能在大体全切除后复发。不同的免疫组化方法对脑膜瘤预后的评价已经有了大量的研究。通过对271例脑膜瘤的免疫组化分析，探讨p16INK4a、p14ARF、p18INK4c、p21CIP1、p27KIP1和p73的表达对预后的意义。对所有肿瘤进行增殖标记物Ki-67和DNA拓扑异构酶II α (topolalpha)染色。3级脑膜瘤中p16INK4a-、p18INK4c-和p21cipi阳性病例数差异有统计学意义。p16INK4a-和p21cip阳性肿瘤在良性脑膜瘤中普遍存在，而p18INK4c免疫染色与间变性脑膜瘤密切相关。复发性脑膜瘤队列中p16INK4a-和p21cip阳性病例的数量明显减少。相比之下，p18ink4c阳性病例聚集在复发脑膜瘤中，与肿瘤分级无关。p14ARF、p27KIPI和p73的免疫反应性在不同组织学和临床结局的脑膜瘤之间没有任何差异。多因素分析显示，肿瘤分级和Topolla指数是预测脑膜瘤复发的独立标准。因此，脑膜瘤中p16INK4a、p14ARF、p18INK4c、p21CIP1、p27KIP1和p73表达的免疫组化评估似乎不能提供有用的预后信息。需要进一步的研究来确定更可靠的预后标志物，并更详细地解决细胞周期畸变在这些肿瘤中的作用。(C) 2003 Wiley-Liss, Inc。
Routine pathological examination cannot distinctively predict the clinical course of meningiomas because even histologically benign tumors may recur after gross total resection. Numerous efforts have been made for the evaluation of different immunohistochemical assays in meningioma prognosis. We investigated the prognostic significance of p16INK4a, p14ARF, p18INK4c, p21CIP1, p27KIP1 and p73 expression by immunohistochemical analysis of 271 meningiomas. All tumors were additionally stained for the proliferation markers Ki-67 and DNA topoisomerase II alpha (Topollalpha). Significant differences between the number of p16INK4a-, p18INK4c- and p21CIPI-positive cases were noted among the 3 grades of meningiomas. p16INK4a- and p21CIP-positive tumors were found to prevail among benign meningiomas, whereas p18INK4c immunostaining was closely associated to anaplastic meningiomas. The number of p16INK4a- and p21CIP-positive cases was significantly lower in the cohort of recurrent meningiomas. In contrast, p18INK4c-positive cases were clustered among recurrent meningiomas regardless of tumor grade. Immuncoreactivity of p14ARF, p27KIPI and p73 did not show any differences between meningiomas of various histology and clinical outcomes. Multivariate analysis revealed that only tumor grade and Topolla index are independent criteria for predicting meningioma recurrence. Thus, the immunohistochemical assessment of p16INK4a, p14ARF, p18INK4c, p21CIP1, p27KIP1 and p73 expression in meningiomas does not appear to provide prognostically useful information. Further studies are needed to identify more reliable prognostic markers and to address in more detail the role of cell cycle aberrations in these tumors. (C) 2003 Wiley-Liss, Inc.