Protoporphyrin IX (PpIX) Fluorescence during Meningioma Surgery: Correlations with Histological Findings and Expression of Heme Pathway Molecules

SIMPLE SUMMARY: In meningiomas, 5-aminolevulinc acid (5-ALA)-mediated fluorescence-guided resection (FGR) has been shown to improve intraoperative tumor bone and soft tissue invasion. However, several studies reported distinct limitations of FGR, e.g., for the visualization of the dura tail or CNS invasion. Notably, correlations between fluorescence and histological findings, as well as the expression of key heme synthesis pathway molecules, have been sparsely investigated. In this study, we examined 111 samples from 44 patients after an FGR of an intracranial meningioma for the presence of histopathological evidence of tumor tissue and intraoperative fluorescence, and analyzed the expression of key transporters/enzymes involved in PpIX metabolism using immunohistochemistry and qPCR. High sensitivity and specificity for the identification of tumor tissue and correlation of fluorescence and tumor tissue with expression of the enzymes/transporters were demonstrated. However, a deviating fluorescence and expression could be observed in non-neoplastic brain tissue, whereas this was lacking in the dura. ABSTRACT: Background: The usefulness of 5-ALA-mediated fluorescence-guided resection (FGR) in meningiomas is controversial, and information on the molecular background of fluorescence is sparse. Methods: Specimens obtained during 44 FGRs of intracranial meningiomas were analyzed for the presence of tumor tissue and fluorescence. Protein/mRNA expression of key transmembrane transporters/enzymes involved in PpIX metabolism (ABCB6, ABCG2, FECH, CPOX) were investigated using immunohistochemistry/qPCR. Results: Intraoperative fluorescence was observed in 70 of 111 specimens (63%). No correlation was found between fluorescence and the WHO grade (p = 0.403). FGR enabled the identification of neoplastic tissue (sensitivity 84%, specificity 67%, positive and negative predictive value of 86% and 63%, respectively, AUC: 0.75, p < 0.001), and was improved in subgroup analyses excluding dura specimens (86%, 88%, 96%, 63% and 0.87, respectively; p < 0.001). No correlation was found between cortical fluorescence and tumor invasion (p = 0.351). Protein expression of ABCB6, ABCG2, FECH and CPOX was found in meningioma tissue and was correlated with fluorescence (p < 0.05, each), whereas this was not confirmed for mRNA expression. Aberrant expression was observed in the CNS. Conclusion: FGR enables the intraoperative identification of meningioma tissue with limitations concerning dura invasion and due to ectopic expression in the CNS. ABCB6, ABCG2, FECH and CPOX are expressed in meningioma tissue and are related to fluorescence.