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Genetic factors affecting intraoperative 5-aminolevulinic acid-induced fluorescence of diffuse gliomas

Kiyotaka Saito
Kiyotaka Saito
, 
Toshinori Hirai
Toshinori Hirai
, 
Hideo Takeshima
Hideo Takeshima
, 
Yoshihito Kadota
Yoshihito Kadota
, 
Shinji Yamashita
Shinji Yamashita
, 
Asya Ivanova
Asya Ivanova
 y 
Kiyotaka Yokogami
Kiyotaka Yokogami
   | 12 abr 2017
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Article Category: Research Articles
Publicado en línea: 12 abr 2017
Páginas: 142 - 150
Recibido: 15 dic 2016
Aceptado: 13 mar 2017
DOI: https://doi.org/10.1515/raon-2017-0019
© 2017 Kiyotaka Saito, Toshinori Hirai, Hideo Takeshima, Yoshihito Kadota, Shinji Yamashita, Asya Ivanova, Kiyotaka Yokogami
This article is distributed under the terms of the Creative Commons Attribution Non-Commercial License, which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited.

Comparison of tumor characteristics on MRI scans. Axial T2W images showing a mass with (A) a smooth and (B) an indistinct tumor border in the left frontal lobe, (C) homogeneous intensity in the right frontal lobe, and (D) heterogeneous intensity in the left thalamus. Axial gadolinium-enhanced T1W images show that (E) the tumor lacks contrast enhancement in the right frontal lobe and is (F) contrast-enhanced in the left parietal lobe.
Comparison of tumor characteristics on MRI scans. Axial T2W images showing a mass with (A) a smooth and (B) an indistinct tumor border in the left frontal lobe, (C) homogeneous intensity in the right frontal lobe, and (D) heterogeneous intensity in the left thalamus. Axial gadolinium-enhanced T1W images show that (E) the tumor lacks contrast enhancement in the right frontal lobe and is (F) contrast-enhanced in the left parietal lobe.

Appearance of the tumor cavity under the surgical microscope. (A-B) Violet-blue light excitation yielding visible 5-ALA fluorescence. Note robust (lava-like orange) (A) and mild (pink) brightness (B). (C) No 5-ALA fluorescence is visualized in the tumor cavity.
Appearance of the tumor cavity under the surgical microscope. (A-B) Violet-blue light excitation yielding visible 5-ALA fluorescence. Note robust (lava-like orange) (A) and mild (pink) brightness (B). (C) No 5-ALA fluorescence is visualized in the tumor cavity.

Schematic illustration of the relationship between heme synthesis and the IDH1 mutation. Thick arrows indicate metabolism activation, white arrows the activated enzymes or plasma membrane structures involved in porphyrin metabolism. ABCG2 transports porphyrins from the cytoplasm to the extracellular space. NADP+ levels increase during metabolization to bilirubin by heme. The IDH1 mutation may promote a defense system against ROS by activating catalase, HO-1, etc. The intracellular PPIX level is downregulated. (ABCG2 = ATP-binding cassette transporter G2; CO = carbon monoxide; FECH = ferrochelatase; HO-1 = heme oxygenase-1; PP = protoporphyrin; ROS = reactive oxygen species).
Schematic illustration of the relationship between heme synthesis and the IDH1 mutation. Thick arrows indicate metabolism activation, white arrows the activated enzymes or plasma membrane structures involved in porphyrin metabolism. ABCG2 transports porphyrins from the cytoplasm to the extracellular space. NADP+ levels increase during metabolization to bilirubin by heme. The IDH1 mutation may promote a defense system against ROS by activating catalase, HO-1, etc. The intracellular PPIX level is downregulated. (ABCG2 = ATP-binding cassette transporter G2; CO = carbon monoxide; FECH = ferrochelatase; HO-1 = heme oxygenase-1; PP = protoporphyrin; ROS = reactive oxygen species).

Relationsh ip between 5-aminolevulinic acid-induced fluorescence (5-ALA) status and clinical-pathologic features

Clinical-pathologic featuresPatients with visible fluorescence (n=42)Patients with no visible fluorescence (n=18)P valueχ2, Fisher, or Student t test
Age (years)
Average ± SD62.4 ± 16.456.7 ± 12.50.16-
IDH1 mutation<0.00123.57
Positive211
Negative407
1p19q LOH0.00310.22
Positive59
Negative379
MGMT methylation0.054.35
Positive1813
Negative245
MIB1 LI (%)
Average ± SD38.5 ± 20.720.2 ± 22.80.007-
Tumor margin0.0464.88
Irregular276
Smooth1512
T2 Heterogeneity0.0216.48
Homo25
Hetero4013
Contrast enhancement0.00211.71
Positive4112
Negative16

Clinical characteristics of 60 patients with diffuse gliomas

CharacteristicsNo. of Patients (%)
Number of patients60 (100)
Sex
 Male35 (58.3)
 Female25 (41.7)
Age (yrs)
 Average ± SD60.7 ± 15.4
 Median62.5
 Range6 - 80
Tumor grades and subtypes (WHO 2007)
Grade II8 (13.3)
 Astrocytoma2 (3.3)
 Oligoastrocytoma3 (5.0)
 Oligodendroglioma3 (5.0)
Grade III17 (28.3)
 Anaplastic astrocytoma2 (3.3)
 Anaplastic oligoastrocytoma3 (5.0)
 Anaplastic oligodendroglioma12 (20.0)
Grade IV35 (58.3)
Localization
 Frontal22 (36.7)
 Fronto-temporal2 (3.3)
 Temporal9 (15.0)
 Temporo-parietal5 (8.3)
 Temporal & insular2 (3.3)
 Parietal4 (6.7)
 Parieto-occipital2 (3.3)
 Occipital0 (0)
 Insular4 (6.7)
 Central8 (13.3)
 Cerebellar2 (3.3)
Tumor Status
 Primary54 (90.0)
 Recurrence6 (10.0)

Multivariate analysis of significant factors from univariate analysis

FactorP ValueOdds ratio95% confidence interval
IDH1 wild type0.00919.2381.39, 175.39
1p19q LOH0.1980.3010.05, 1.87
MIB-1 labeling index0.1571.0330.99, 1.08
Tumor margin0.7430.7200.10, 5.15
T2 heterogeneity0.4702.7630.18, 43.44
Contrast enhancement0.3454.1070.22, 77.32

5-aminolevulinic acid-induced fluorescence (5-ALA) in 60 diffuse gliomas

5-ALA fluorescenceWHO grade IIWHO grade IIIWHO grade IV
Positive2/8 (25 %)9/17 (53 %)31/35 (89%)
Negative6/8 (75 %)8/17 (47 %)4/35 (11%)
eISSN:
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Temas de la revista:
Medicine, Clinical Medicine, Radiology, Internal Medicine, Haematology, Oncology
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