Molecular investigation of brain tumors progressing during pregnancy or postpartum period: the association between tumor type, their receptors, and the timing of presentation

Objective: 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. Methods: 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. Results: 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. Conclusion: 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.