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

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 tiss...

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Published inCancers Vol. 15; no. 1; p. 304
Main Authors Spille, Dorothee C, Bunk, Eva C, Thomas, Christian, Özdemir, Zeynep, Wagner, Andrea, Akkurt, Burak H, Mannil, Manoj, Paulus, Werner, Grauer, Oliver M, Stummer, Walter, Senner, Volker, Brokinkel, Benjamin
Format Journal Article
LanguageEnglish
Published Switzerland MDPI AG 01.01.2023
MDPI
Subjects
5-aminolevulinic acid
ABCB6
ABCG2
Biosynthesis
Bone tumors
Brain cancer
Care and treatment
CPOX
Ectopic expression
Enzymes
FECH
Fluorescence
Gene expression
Genetic aspects
Health aspects
Heme
Immunohistochemistry
Light
Manufacturers
Meningioma
Metabolism
Methods
Microscopy
Neuropathology
Optical properties
Patients
Porphyrins
Protoporphyrin
Protoporphyrin IX
Surgery
Tumors
Visualization
Germany
meningioma
ABCB6
FECH
fluorescence
CPOX
protoporphyrin
5-aminolevulinic acid
ABCG2
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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.
AbstractList 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.
Simple SummaryIn 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.AbstractBackground: 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.
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.
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. 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.
Audience Academic
Author Thomas, Christian
Wagner, Andrea
Özdemir, Zeynep
Stummer, Walter
Bunk, Eva C
Paulus, Werner
Senner, Volker
Brokinkel, Benjamin
Spille, Dorothee C
Akkurt, Burak H
Grauer, Oliver M
Mannil, Manoj
AuthorAffiliation 2 Institute of Neuropathology, University Hospital Münster, 48149 Münster, Germany
4 Department of Neurology with Institute of Translational Neurology, University Hospital Münster, 48149 Münster, Germany
1 Department of Neurosurgery, University Hospital Münster, Albert-Schweitzer-Campus 1, Building A1, 48149 Münster, Germany
3 Department of Radiology, University Hospital Münster, 48149 Münster, Germany
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CitedBy_id crossref_primary_10_3390_cancers15194890
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Issue 1
Keywords meningioma
ABCB6
FECH
fluorescence
CPOX
protoporphyrin
5-aminolevulinic acid
ABCG2
Language English
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These authors contributed equally to this work.
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Snippet Background: The usefulness of 5-ALA-mediated fluorescence-guided resection (FGR) in meningiomas is controversial, and information on the molecular background...
In meningiomas, 5-aminolevulinc acid (5-ALA)-mediated fluorescence-guided resection (FGR) has been shown to improve intraoperative tumor bone and soft tissue...
Simple SummaryIn meningiomas, 5-aminolevulinc acid (5-ALA)-mediated fluorescence-guided resection (FGR) has been shown to improve intraoperative tumor bone and...
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StartPage 304
SubjectTerms 5-aminolevulinic acid
ABCB6
ABCG2
Biosynthesis
Bone tumors
Brain cancer
Care and treatment
CPOX
Ectopic expression
Enzymes
FECH
Fluorescence
Gene expression
Genetic aspects
Health aspects
Heme
Immunohistochemistry
Light
Manufacturers
Meningioma
Metabolism
Methods
Microscopy
Neuropathology
Optical properties
Patients
Porphyrins
Protoporphyrin
Protoporphyrin IX
Surgery
Tumors
Visualization
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Title Protoporphyrin IX (PpIX) Fluorescence during Meningioma Surgery: Correlations with Histological Findings and Expression of Heme Pathway Molecules
URI https://www.ncbi.nlm.nih.gov/pubmed/36612300
https://www.proquest.com/docview/2761099832/abstract/
https://search.proquest.com/docview/2761977553
https://pubmed.ncbi.nlm.nih.gov/PMC9818642
https://doaj.org/article/a80dcce00dfa4726b53171b360153860
Volume 15
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