Department of Neurosurgery, Keio University, School of Medicine, Tokyo, Japan.
Department of Pathology, Keio University, School of Medicine, Tokyo, Japan.
Clin Neurol Neurosurg. 2021 Aug;207:106720. doi: 10.1016/j.clineuro.2021.106720. Epub 2021 Jun 1.
Brain tumors often become clinically evident during pregnancy; however, the mechanism has not been well elucidated. Purpose of this study is to investigate the influence of molecular genetic factors on the progression of brain tumors during pregnancy or the postpartum period.
Twelve cases of brain tumors that presented during pregnancy or postpartum period were included: five gliomas, three meningiomas, two vestibular schwannomas, and two chordomas. Tumor samples were investigated by metaphase comparative genomic hybridization and immunohistochemistry, for chromosomal copy number aberration (CNA) and receptor expression of sex hormones and growth factors.
The results were correlated with the timing of tumor presentation in relation to the stage of pregnancy. EGFR, VEGFR-1/2, AR, and c-Myc were expressed in gliomas, PgR, ER, HER-2, VEGFR-1, EGF and VEGFR2 in meningiomas, VEGFR-1 in vestibular schwannomas, and EGFR, VEGFR-1/2, and c-Myc in chordomas. The CNAs of the tumors varied. Four of the five gliomas presented in the 2nd trimester, all three meningiomas in the 3rd trimester or postpartum period, and both of the two schwannomas in the late 2nd trimester. Expression of VEGFR-1/2 and EGFR was observed regardless of the timing of tumor presentation, whereas female hormone receptors and HER-2 were exclusively found in meningiomas. Interestingly, one anaplastic astrocytoma (IDH mut, non-codeleted) that progressed from precedent grade 2 tumor harbored amplification of the MYC locus.
Progression of brain tumors during pregnancy is associated with various growth factors as well as sex hormones. The timing of presentation is likely dependent on molecular receptors specific to each tumor type.
脑肿瘤在妊娠期间常表现为临床显性;然而,其机制尚未完全阐明。本研究旨在探讨分子遗传因素对妊娠或产后期间脑肿瘤进展的影响。
纳入了 12 例妊娠或产后期间出现的脑肿瘤病例:5 例胶质瘤、3 例脑膜瘤、2 例前庭神经鞘瘤和 2 例脊索瘤。通过中期比较基因组杂交和免疫组织化学技术,对肿瘤样本进行染色体拷贝数异常(CNA)和性激素及生长因子受体表达分析。
结果与肿瘤发生与妊娠阶段的时间相关。EGFR、VEGFR-1/2、AR 和 c-Myc 在胶质瘤中表达,PgR、ER、HER-2、VEGFR-1、EGF 和 VEGFR2 在脑膜瘤中表达,VEGFR-1 在前庭神经鞘瘤中表达,EGFR、VEGFR-1/2 和 c-Myc 在脊索瘤中表达。肿瘤的 CNA 存在差异。5 例胶质瘤中有 4 例在妊娠中期出现,3 例脑膜瘤均在妊娠晚期或产后出现,2 例神经鞘瘤均在妊娠晚期出现。VEGFR-1/2 和 EGFR 的表达与肿瘤发生的时间无关,而女性激素受体和 HER-2 仅在脑膜瘤中发现。有趣的是,一例从先前的 2 级肿瘤进展而来的间变性星形细胞瘤(IDHmut,非缺失)携带 MYC 基因座的扩增。
妊娠期间脑肿瘤的进展与多种生长因子以及性激素有关。肿瘤发生的时间可能取决于每种肿瘤类型的特定分子受体。