Alteration of FOXM1 expression and macrophage polarization in refractory meningiomas during long-term follow-up.
Alteration of FOXM1 expression and macrophage polarization in refractory meningiomas during long-term follow-up.
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长期随访期间难治性脑膜瘤中 FOXM1 表达和巨噬细胞极化的变化。
DOI：
10.21037/tcr-20-1896
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发表时间：
2021-01
影响因子：
0.9
通讯作者：
Murayama Y
中科院分区：
文献类型：
--
作者：
Takei J;Tanaka T;Teshigawara A;Tochigi S;Hasegawa Y;Murayama Y
潜伏期长的I级脑膜瘤恶性进展是罕见的。我们经历了II/III级脑膜瘤与难治性和复发的I级脑膜瘤通过多次手术。本研究纳入了3例非典型/间变性脑膜瘤患者，这些患者在I级（脑膜瘤）脑膜瘤初次手术后经历了长期潜伏性复发，未接受辅助放疗。所有病例（病例1、2和3）的初始肿瘤的组织学结果显示脑膜瘤分别含有1%、5%和0.1%的MIB-1阳性细胞。令人惊讶的是，磁共振成像（MRI）分别在初次手术后2年、12年和12年检测到肿瘤复发。例1为第三次复发后的不典型脑膜瘤，例2和例3分别为第二次和第三次复发后的间变性脑膜瘤。例2患者接受了辅助放疗。例2肿瘤颅内复发，肺转移伴大量胸腔积液。为了探讨良性脑膜瘤恶性进展的发病机制，采用免疫组化法和RT-PCR法对所有3例患者的初始和复发肿瘤的手术标本进行了CD 163/CD 68表达和FOXM 1 mRNA表达的比较。复发肿瘤中CD 163/CD 68阳性率和FOXM 1 mRNA表达均高于初发肿瘤。CD 163和FOXM 1的表达水平诱导即使在复发的I级脑膜瘤，表明巨噬细胞极化和促有丝分裂转录因子可能与脑膜瘤的临床行为，并作为一个有用的预测指标恶性进展。仔细的长期随访对于脑膜瘤恶性进展的早期诊断是重要的，即使I级脑膜瘤被完全切除。包括放射和新型分子靶向治疗在内的多学科方法的发展有望用于复发性和恶性脑膜瘤。
Malignant progression of grade I meningioma with a long latency period is rare. We experienced grade II/III meningiomas with refractoriness and recurrence from grade I meningiomas through multiple surgeries. Three patients with atypical/anaplastic meningioma experienced long-latent recurrence after initial surgery for grade I (meningothelial) meningioma without following adjuvant radiotherapy were included in the present study. Histological findings of the initial tumors in all cases (case 1, 2, and 3) revealed meningothelial meningioma with 1%, 5%, and 0.1% MIB-1 positive cells, respectively. Surprisingly, magnetic resonance imaging (MRI) detected a recurrent tumor 2, 12, and 12 years after the initial operation, respectively. Case 1 was atypical meningioma after third recurrence, and case 2 and 3 were anaplastic meningioma after second and third recurrence, respectively. The patient in case 2 received adjuvant radiotherapy. In case 2, the tumor recurred intracranial and distant metastasis to the lung with huge substantial pleural effusion was detected. To investigate the pathogenesis of malignant progression from benign to malignant meningioma, CD163/CD68 expression by immunohistochemically and FOXM1 mRNA expression by RT-PCR were compared using surgical specimens from initial and recurrent tumors in all three patients. The ratio of CD163/CD68 positivity and FOXM1 mRNA expression were increased in recurrent tumors compared with matched initial tumors. CD163 and FOXM1 expression levels were induced even in recurrent grade I meningioma, suggesting that macrophage polarization and pro-mitotic transcriptional factor might be associated with clinical behavior of meningioma and be useful as a prediction marker for malignant progression. Careful long-term follow-up is important for early diagnosis of malignant progression in meningiomas, even if grade I meningioma is completely resected. Development of a multidisciplinary approach including radiation and novel molecular targeted therapy is expected for recurrent and malignant meningiomas.