Oxidative stress is related to the formation of Antoni B patterns and eosinophilic hyaline droplets in schwannomas.
Schwannomas, particularly of vestibular origin, often accompany degenerative hypocellular areas known as Antoni B patterns; however, the detailed mechanism is uncertain. Eosinophilic hyaline droplets (EHD), the substantial nature of which are autophagic vacuoles, preferentially appear in acoustic schwannomas and distribute around areas of Antoni B. We investigated their common background using schwannomas with (15 cases) or without (10 cases) EHD, and demonstrated that EHD showed selective immunoreactivity with an anti-nitrotyrosine antibody, suggesting the overproduction of nitric oxide in this condition. The expression of inducible nitric oxide synthase was emphasized in infiltrating macrophages around hyalinized vessels. Protein-bound 4-hydroxy 2-nonenal, another oxidative stress marker, was detected in Antoni B tissue, but not in EHD. Antibodies to cleaved caspase-3 and single strand DNA, indicators of apoptosis, did not label tumors cells in Antoni B areas as well as EHD-bearing cells. The morphology and the mitotically static state of EHD-laden cells are phenotypically similar to autophagic cell death; however, autophagy in normal cells is a cell survival strategy against starvation, so the possibility remains that EHD are formed in that context. In either case, schwannomas may show a characteristic autophagic change by an endogenous mechanism. Tumor growth in a narrow intracranial space and resultant ischemia by self-oppression were postulated to be an initial event, because ischemia-reperfusion injury is a major source of reactive oxygen species and ischemia is also a potent trigger of autophagy as well as of tissue degeneration. Moreover, potential roles of chemokines and hemosiderosis are discussed.
Yokoo
Hideaki
H
Department of Human Pathology, Gunma University Graduate School of Medicine, 3-39-22 Showa-machi, Maebashi, Gunma 371-8511, Japan. yokoo@med.gunma-u.ac.jp
Oishi
Takuma
T
Isoda
Koji
K
Nakazato
Yoichi
Y
Toyokuni
Shinya
S
D000080242:8-Hydroxy-2'-Deoxyguanosine; D000447:Aldehydes / Q000378:metabolism; D053399:Apolipoproteins D / Q000378:metabolism; D001343:Autophagy / Q000502:physiology; D053148:Caspase 3 / Q000378:metabolism; D003849:Deoxyguanosine / Q000031:analogs & derivatives / Q000378:metabolism; D005260:Female; D006801:Humans; D006818:Hyalin / Q000378:metabolism / Q000648:ultrastructure*; D007150:Immunohistochemistry; D002479:Inclusion Bodies / Q000378:metabolism / Q000648:ultrastructure*; D008297:Male; D008875:Middle Aged; D009442:Neurilemmoma / Q000473:pathology* / Q000503:physiopathology*; D052247:Nitric Oxide Synthase Type II / Q000378:metabolism; D018384:Oxidative Stress / Q000502:physiology*; D014443:Tyrosine / Q000031:analogs & derivatives / Q000378:metabolism
D000447:Aldehydes; D053399:Apolipoproteins D; C002744:3-nitrotyrosine; D014443:Tyrosine; D000080242:8-Hydroxy-2'-Deoxyguanosine; D052247:Nitric Oxide Synthase Type II; D053148:Caspase 3; D003849:Deoxyguanosine; C027576:4-hydroxy-2-nonenal