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

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.

Fluorescence and immune-cell infiltration of nonneoplastic, postbrachytherapy brain tissue in 5-ALA–guided resection of recurrent anaplastic meningioma: illustrative case

“…Postoperative tumor volume has been found to be a significant predictor of tumor recurrence in meningioma. 27 A large cohort study of 204 cases showed that 5-ALA-induced PpIX fluorescence was successful at enabling intraoperative visualization of most intracranial meningiomas as well as tumor-infiltrated bone flaps. 2 The uptake of 5-ALA into cells of the brain, both normal cortex and tumor tissue, is predicated on 5-ALA bioavailability in the microenvironment.…”

Intraoperative Imaging and Optical Visualization Techniques for Brain Tumor Resection: A Narrative Review

“…New targeted fluorophores can bind to tumor-specific markers such as the epidermal growth factor receptor (EGFR) and other peptides [65][66][67][68]. 5-ALA has been the most exhaustively studied FGS agent for HGGs and most recently meningiomas due to its robust red fluorescence in the tumor bulk and predictive value for delineating tumor tissue versus surrounding brain parenchyma [69,70]. 5-ALA is the only FDA-approved agent for use during glioma surgery [71].…”

“…5-ALA is the only FDA-approved agent for use during glioma surgery [71]. Correlations have also been observed between fluorescence intensity and histological grading, suggesting an ability to approximate tumor grade by fluorescent signal [6,54,69,70]. Despite its promising advantages, the use of 5-ALA comes with certain drawbacks.…”