Prognostic significance of Ki-67 (MIB-1) proliferation index in childhood primitive neuroectodermal tumors of the central nervous system.
Prognostic significance of Ki-67 (MIB-1) proliferation index in childhood primitive neuroectodermal tumors of the central nervous system.
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DOI：
10.1002/1096-911x(20010201)36:2
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发表时间：
2001-02
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通讯作者：
Michael A. Grotzer;Birgit Geoerger;A. Janss;Huaqing Zhao;Lucy B. Rorke;Peter C. Phillips
中科院分区：
文献类型：
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作者：
Michael A. Grotzer;Birgit Geoerger;A. Janss;Huaqing Zhao;Lucy B. Rorke;Peter C. Phillips
背景中枢神经系统原始神经外胚层肿瘤（PNET），包括髓母细胞瘤，是儿童最常见的恶性脑肿瘤。虽然一些患者在手术和辅助治疗后经历了长期的疾病控制，但其他具有类似肿瘤的患者会复发并最终死于疾病进展。由于增殖活性可能与生物侵袭性有潜在的相关性，我们用Ki-67 （MIB-1）免疫组织化学方法对78例特征明确的PNETs患者进行了评估。通过计数Ki-67 （MIB-1）阳性肿瘤细胞在最高染色区域（热点PI）或至少15个随机选择的区域（随机PI）来测定增殖指数（PI）。结果78例PNETs中有25例热点PI值（中位数9.3%，范围0.6-56%）比随机PI值（中位数5.6%，范围0.2-41.3%）高出2倍以上，单因素Cox回归分析显示，热点PI高的PNETs的进展和死亡风险显著高于热点PI低的PNETs（风险比1.58,P = 0.04）。在多变量分析中调整m期后，风险比仍然显著。与热点PI相反，随机PI被证明不是一个显著的预后预测因子。结论热点PI是PNETs重要且独立的预后因素。其评估简单、可靠，可作为常规组织学检查的补充，作为提高预测儿童PNETs生物学行为准确性的手段。
BACKGROUND Primitive neuroectodermal tumors (PNET) of the central nervous system, including medulloblastomas, are the most common malignant brain tumors of childhood. Whereas some patients experience prolonged disease control after surgery and adjuvant therapy, others with tumors that appear comparable will relapse and eventually die from progressive disease. PROCEDURE Because proliferative activity may provide a potential correlate of biologic aggressiveness, PNETs of 78 well-characterized patients were evaluated by Ki-67 (MIB-1) immunohistochemistry. Proliferation indices (PI) were determined by counting Ki-67 (MIB-1) positive tumor cells either in the highest staining region (hot spot PI), or in at least 15 randomly chosen fields (random PI). RESULTS Twenty-five of 78 PNETs showed amore than twofold higher value of hot spot PI (median 9.3%; range 0.6-56%), compared to random PI (median 5.6%; range 0.2-41.3%), Univariate Cox regression analysis revealed that PNETs with a high hot spot PI had a significantly greater risk of progression and death than PNETs with a low hot spot PI (hazard ratio 1.58, P = 0.04). The hazard ratio remained significant after adjusting for M-stage in multivariate analysis. In contrast to hot spot PI, random PI proved not to be a significant prognostic predictor. CONCLUSIONS Hot spot PI is a significant and independent prognostic factor in PNETs. Its assessment is uncomplicated, reliable, and may supplement routine histologic examination as a means for improving the accuracy of predicting the biologic behavior of childhood PNETs.