Ningning Zhang and Zhende Shang contributed equally to this work.
This study aimed to analyze the relationship between molecular pathologic expression of GFAP and Ki-67 and fluorescence levels, and to provide molecular pathological basis for the removal of malignant gliomas (MG) by Fluorescein Sodium (FLS) navigation under the YELLOW 560 nm surgical microscope filter.
A retrospective analysis of clinical data of 18 MG cases confirmed by the postoperative pathology was performed. All cases were resected by FLS guiding under the YELLOW 560 nm filter. Hematoxylin-eosin (HE) staining, molecular pathology markers GFAP, and Ki-67 immunohistochemical staining of the specimens were performed. The relationship between fluorescence staining levels and GFAP positive rate, Ki-67 proliferation index, and WHO grades was studied.
There were 69 pathological specimens with fluorescence levels of “bright” fluorescence (n = 32), “low” fluorescence (n = 18), and “no” fluorescence (n = 19). Immunohistochemical staining showed GFAP-positive expression in both tumor cells and normal glial cells. The staining levels of the specimens in the fluorescence regions were higher than that in the non-fluorescence regions. GFAP expression was positive in 61 specimens and negative in 8 specimens. Comparison of Ki-67 proliferation index using chi-square test showed different fluorescence levels had different Ki-67 proliferation indexes (χ2 = 14.678, p = 0.005). With high proliferation index of specimens, fluorescence level was brighter. WHO grade had no correlation with fluorescence levels (χ2 = 3.531, p = 0.171).
FLS-guided resection of MG is safe and effective. In the boundary area of MG, fluorescence levels and Ki-67 proliferation index showed correlation. FLS-guided resection achieved the function of “reducing tumor cell,” thus reducing the proliferation index in the lesion area.
Ostrom QT, Gittleman H, Liao P, Rouse C, Chen Y, Dowling J, et al. CBTRUS statistical report: primary brain and central nervous system tumors diagnosed in the United States in 2007-2011. Neuro-Oncology. 2014;16(Suppl 4):iv1–63. CrossRef
Orringer D, Lau D, Khatri S, Zamora-Berridi GJ, Zhang K, Wu C, et al. Extent of resection in patients with glioblastoma: limiting factors, perception of resectability, and effect on survival. J Neurosurg. 2012;117:851–9. CrossRef
Salvati M, Pichierri A, Piccirilli M, Floriana Brunetto GM, D'Elia A, Artizzu S, et al. Extent of tumor removal and molecular markers in cerebral glioblastoma: a combined prognostic factors study in a surgical series of 105 patients. J Neurosurg. 2012;117:204–11. CrossRef
Stummer W, Pichlmeier U, Meinel T, Wiestler OD, Zanella F, Reulen HJ, et al. Fluorescence-guided surgery with 5-aminolevulinic acid for resection of malignant glioma: a randomised controlled multicentre phase III trial. Lancet Oncol. 2006;7:392–401. CrossRef
Li YM, Suki D, Hess K, Sawaya R. The influence of maximum safe resection of glioblastoma on survival in 1229 patients: can we do better than gross-total resection? J Neurosurg. 2016;124:977–88. CrossRef
Stendel R. Extent of resection and survival in glioblastoma multiforme: identification of and adjustment for bias. Neurosurgery. 2009;64:E1206 author reply E. CrossRef
Schebesch KM, Proescholdt M, Hohne J, Hohenberger C, Hansen E, Riemenschneider MJ, et al. Sodium fluorescein-guided resection under the YELLOW 560 nm surgical microscope filter in malignant brain tumor surgery--a feasibility study. Acta Neurochir. 2013;155:693–9. CrossRef
Acerbi F, Broggi M, Eoli M, Anghileri E, Cavallo C, Boffano C, et al. Is fluorescein-guided technique able to help in resection of high-grade gliomas? Neurosurg Focus. 2014;36:E5. CrossRef
Wen PY, Macdonald DR, Reardon DA, Cloughesy TF, Sorensen AG, Galanis E, et al. Updated response assessment criteria for high-grade gliomas: response assessment in neuro-oncology working group. J Clin Oncol. 2010;28:1963–72. CrossRef
Cordella R, Acerbi F, Broggi M, Vailati D, Nazzi V, Schiariti M, et al. Intraoperative neurophysiological monitoring of the cortico-spinal tract in image-guided mini-invasive neurosurgery. Clin Neurophysiol. 2013;124:1244–54. CrossRef
Ferroli P, Acerbi F, Albanese E, Tringali G, Broggi M, Franzini A, et al. Application of intraoperative indocyanine green angiography for CNS tumors: results on the first 100 cases. Acta Neurochir Suppl. 2011;109:251–7. CrossRef
Stummer W, Stocker S, Wagner S, Stepp H, Fritsch C, Goetz C, et al. Intraoperative detection of malignant gliomas by 5-aminolevulinic acid-induced porphyrin fluorescence. Neurosurgery. 1998;42:518–25 discussion 25–6. CrossRef
Moore GE. Fluorescein as an agent in the differentiation of normal and malignant tissues. Science. 1947;106:130–1. CrossRef
Moore GE, Peyton WT, et al. The clinical use of fluorescein in neurosurgery; the localization of brain tumors. J Neurosurg. 1948;5:392–8. CrossRef
Shinoda J, Yano H, Yoshimura S, Okumura A, Kaku Y, Iwama T, et al. Fluorescence-guided resection of glioblastoma multiforme by using high-dose fluorescein sodium. Technical note J Neurosurg. 2003;99:597–603. CrossRef
Chen B, Wang H, Ge P, Zhao J, Li W, Gu H, et al. Gross total resection of glioma with the intraoperative fluorescence-guidance of fluorescein sodium. Int J Med Sci. 2012;9:708–14. CrossRef
Koc K, Anik I, Cabuk B, Ceylan S. Fluorescein sodium-guided surgery in glioblastoma multiforme: a prospective evaluation. Br J Neurosurg. 2008;22:99–103. CrossRef
Kuroiwa T, Kajimoto Y, Ohta T. Development of a fluorescein operative microscope for use during malignant glioma surgery: a technical note and preliminary report. Surg Neurol. 1998;50:41–8 discussion 8-9. CrossRef
de Armond SJ, Eng LF, Rubinstein LJ. The application of glial fibrillary acidic (GFA) protein immunohistochemistry in neurooncology. A progress report Pathol Res Pract. 1980;168:374–94. CrossRef
Eng LF, Vanderhaeghen JJ, Bignami A, Gerstl B. An acidic protein isolated from fibrous astrocytes. Brain Res. 1971;28:351–4. CrossRef
Raghavan R, Steart PV, Weller RO. Cell proliferation patterns in the diagnosis of astrocytomas, anaplastic astrocytomas and glioblastoma multiforme: a Ki-67 study. Neuropathol Appl Neurobiol. 1990;16:123–33. CrossRef
Merzak A, Koocheckpour S, Pilkington GJ. CD44 mediates human glioma cell adhesion and invasion in vitro. Cancer Res. 1994;54:3988–92. PubMed
Baskan O, Silav G, Sari R, Canoz O, Elmaci I. Relationship of intraoperative ultrasound characteristics with pathological grades and Ki-67 proliferation index in intracranial gliomas. J Med Ultrason (2001). 2015;42:231–7. CrossRef
Torp SH. Diagnostic and prognostic role of Ki67 immunostaining in human astrocytomas using four different antibodies. Clin Neuropathol. 2002;21:252–7. PubMed
Eng LF, Rubinstein LJ. Contribution of immunohistochemistry to diagnostic problems of human cerebral tumors. J Histochem Cytochem. 1978;26:513–22. CrossRef
Kiss R, Dewitte O, Decaestecker C, Camby I, Gordower L, Delbecque K, et al. The combined determination of proliferative activity and cell density in the prognosis of adult patients with supratentorial high-grade astrocytic tumors. Am J Clin Pathol. 1997;107:321–31. CrossRef
Bouvier-Labit C, Chinot O, Ochi C, Gambarelli D, Dufour H, Figarella-Branger D. Prognostic significance of Ki67, p53 and epidermal growth factor receptor immunostaining in human glioblastomas. Neuropathol Appl Neurobiol. 1998;24:381–8. CrossRef
Diaz RJ, Dios RR, Hattab EM, Burrell K, Rakopoulos P, Sabha N, et al. Study of the biodistribution of fluorescein in glioma-infiltrated mouse brain and histopathological correlation of intraoperative findings in high-grade gliomas resected under fluorescein fluorescence guidance. J Neurosurg. 2015;122:1360–9. CrossRef
Neira JA, Ung TH, Sims JS, Malone HR, Chow DS, Samanamud JL, et al. Aggressive resection at the infiltrative margins of glioblastoma facilitated by intraoperative fluorescein guidance. J Neurosurg. 2017;127:111–22. CrossRef
Rodriguez-Pereira C, Suarez-Penaranda JM, Vazquez-Salvado M, Sobrido MJ, Abraldes M, Barros F, et al. Value of MIB-1 labelling index (LI) in gliomas and its correlation with other prognostic factors. A clinicopathologic study. J Neurosurg Sci. 2000;44:203–9 discussion 9-10. PubMed
Kayaselcuk F, Zorludemir S, Gumurduhu D, Zeren H, Erman T. PCNA and Ki-67 in central nervous system tumors: correlation with the histological type and grade. J Neuro-Oncol. 2002;57:115–21. CrossRef
- Molecular pathological expression in malignant gliomas resected by fluorescein sodium-guiding under the YELLOW 560 nm surgical microscope filter
- BioMed Central
Neu im Fachgebiet Chirurgie
e.Med Kampagnen-Visual, Mail Icon II