gms | German Medical Science

63rd Annual Meeting of the German Society of Neurosurgery (DGNC)
Joint Meeting with the Japanese Neurosurgical Society (JNS)

German Society of Neurosurgery (DGNC)

13 - 16 June 2012, Leipzig

Aquaporin 1 and 4 in 5-ALA fluorescent tumor tissue

Meeting Abstract

  • C. Ewelt - Klinik für Neurochirurgie, Westfälische Wilhelms-Universität, Münster
  • H. Ardon - Klinik für Neurochirurgie, Westfälische Wilhelms-Universität, Münster; Katholieke Universiteit Leuven, Leuven, Belgium,; Sint Elisabeth Ziekenhuis, Tilburg, Netherlands
  • E. Suero - Klinik für Neurochirurgie, Westfälische Wilhelms-Universität, Münster
  • D. Günes - Klinik für Neurochirurgie, Westfälische Wilhelms-Universität, Münster
  • J. Schroeteler - Klinik für Neurochirurgie, Westfälische Wilhelms-Universität, Münster
  • J. Wölfer - Klinik für Neurochirurgie, Westfälische Wilhelms-Universität, Münster
  • W. Stummer - Klinik für Neurochirurgie, Westfälische Wilhelms-Universität, Münster

Deutsche Gesellschaft für Neurochirurgie. Japanische Gesellschaft für Neurochirurgie. 63. Jahrestagung der Deutschen Gesellschaft für Neurochirurgie (DGNC), Joint Meeting mit der Japanischen Gesellschaft für Neurochirurgie (JNS). Leipzig, 13.-16.06.2012. Düsseldorf: German Medical Science GMS Publishing House; 2012. DocSA.01.05

DOI: 10.3205/12dgnc303, URN: urn:nbn:de:0183-12dgnc3032

Published: June 4, 2012

© 2012 Ewelt et al.
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Outline

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Objective: Fluorescence-guided surgery with 5-aminolevulinic acid (5-ALA) enables more complete resections of contrast-enhancing malignant gliomas in adults. Aquaporins (AQP) are a family of membrane proteins that provide a major pathway for water transport in mammals. Prior studies have suggested that AQP1 and 4 may be up-regulated in glial tumors, potentially contributing to tumor-associated edema and invasion. The objective of this study was to investigate the expression of AQP1 and 4 in 5-ALA fluorescent tumor tissue which has a high specificity for high-grade malignancies.

Methods: 5-ALA fluorescent samples of different tumor tissue during surgery were analyzed for AQP1 and AQP4 positivity in combination with GFAP (only for gliomas) in selective antibody testing by fluorescent activating cell sorting (FACS). Control groups were normal brain tissue without 5-ALA fluorescence and the human glioma cell line U373. Measurements were performed immediately after resection, 4 days and 14 days after primary cell culture. Furthermore, 5-ALA staining in tumor cells was also proved by FACS. Histopathological and clinical findings of the tumors were correlated with the experimental results.

Results: 18 gliomas (16 high-grades, 2 low-grades), 6 metastases and 3 meningiomas, which all showed a pronounced perifocal edema in the preoperative MR imaging, were analyzed. 85% of the gliomas were AQP4 and GFAP positive, whereas the AQP4-positivity decreased after 4 days cell culture to 65% and after 14 days to only 10%. 66% of the 5-ALA fluorescent metastasis tissue samples and 33% of the 5-ALA fluorescent meningioma tissue samples were AQP4 positive. AQP1 was in none of the specimens after cell culture at any time positive, especially not in combination with GFAP. 5 glial tissue samples without histology of tumor and U373 glioma cell line as control cultures were negative for AQP1 and AQP4 testing, but positive in GFAP. OAS and PFS were significantly lower in samples from high-grade tumors.

Conclusions: FACS is a reliable method for detecting the fluorescence signals of porphyrins and aquaporins in primary cell cultures of tumors. Further, exposure of AQP4 in 5-ALA fluorescent high-grade gliomas, metastases and even meningiomas revealed high sensitivity. In contrast, Aquaporin 1 showed no accord to 5-ALA which is correlated to malignancy. Aquaporin 4 in combination with 5-ALA may offer a selective targeting treatment opportunity which requires further studies.