Csonka T, Murnyák B, Szepesi R, Bencze J, Bognár L, Klekner A, Hortobágyi T
Tibor Hortobágyi, MD, PhD, FRCPath, EFN, Division of Neuropathology, Institute of Pathology, University of Debrecen, 98. Nagyerdeikrt. Debrecen, H-4032, Hungary, phone: +3652255248, e-mail:
Folia Neuropathol. 2016;54(2):114-26. doi: 10.5114/fn.2016.60088.
Although tumour recurrence is an important and not infrequent event in meningiomas, predictive immunohistochemical markers have not been identified yet. The aim of this study was to address this clinically relevant problem by systematic retrospective analysis of surgically completely resected meningiomas with and without recurrence, including tumour samples from patients who underwent repeat surgeries. Three established immunohistochemical markers of routine pathological meningioma work-up have been assessed: the proliferative marker Ki-67 (clone Mib1), the tumour suppressor gene p53 and progesterone receptor (PR). All these proteins correlate with the tumour WHO grade, however the predictive value regarding recurrence and progression in tumour grade is unknown. One hundred and fourteen surgical specimens of 70 meningioma patients (16 male and 54 female) in a 16 years' interval have been studied. All tumours had apparently complete surgical removal. On Mib1, PR and p53 immunostained sections, the percentage of labelled tumour cells, the staining intensity and the multiplied values of these parameters (the histoscore) was calculated. Results were statistically correlated with tumour WHO grade, (sub)type, recurrence and progression in WHO grade at subsequent biopsies. Our results confirmed previous findings that the WHO grade is directly proportional to Mib1 and p53 and is inversely proportional to the PR immunostain. We have demonstrated that Mib1 and p53 have a significant correlation with and predictive value of relapse/recurrence irrespective of the histological subtype of the same WHO grade. As a quantitative marker, Mib1 has the best correlation with a percentage of labelled cells, whereas p53 with intensity and histoscore. In conclusion, the immunohistochemical panel of PR, p53, Mib1 in parallel with applying standard diagnostic criteria based on H and E stained sections is sufficient and reliable to predict meningioma recurrence in surgically completely resected tumours.
尽管肿瘤复发在脑膜瘤中是一个重要且并非罕见的事件,但尚未确定预测性免疫组化标志物。本研究的目的是通过对手术完全切除且有或无复发的脑膜瘤进行系统回顾性分析来解决这一临床相关问题,包括来自接受再次手术患者的肿瘤样本。评估了常规病理脑膜瘤检查的三种既定免疫组化标志物:增殖标志物Ki-67(克隆Mib1)、肿瘤抑制基因p53和孕激素受体(PR)。所有这些蛋白质都与肿瘤WHO分级相关,然而,关于肿瘤分级中复发和进展的预测价值尚不清楚。研究了70例脑膜瘤患者(16例男性和54例女性)在16年间的114份手术标本。所有肿瘤均明显实现了手术完全切除。在Mib1、PR和p53免疫染色切片上,计算标记肿瘤细胞的百分比、染色强度以及这些参数的乘积值(组织学评分)。结果与肿瘤WHO分级、(亚)型、后续活检时WHO分级的复发和进展进行统计学相关分析。我们的结果证实了先前的发现,即WHO分级与Mib1和p53成正比,与PR免疫染色成反比。我们已经证明,无论相同WHO分级的组织学亚型如何,Mib1和p53与复发/再发均具有显著相关性和预测价值。作为定量标志物,Mib1与标记细胞百分比的相关性最佳,而p53与强度和组织学评分相关性最佳。总之,PR、p53、Mib1的免疫组化组合,与基于苏木精和伊红染色切片应用标准诊断标准并行,足以且可靠地预测手术完全切除肿瘤中的脑膜瘤复发。