脳腫瘍血管におけるFactor VIII Related Antigenの微細局在—電顕酵素抗体法による検討

IMMUNOCYTOCHEMICAL LOCALIZATION OF FACTOR VIII-RELATED ANTIGEN IN BLOOD VESSELS OF HUMAN CENTRAL NERVOUS SYSTEM TUMORS

　抄録　電顕酵素抗体法を用いて，脳腫瘍血管，非腫瘍脳組織における第8因子関連抗原（F VIII R：Agと略す）の微細局在について報告した。①F VIII R：Agの分布は，腫瘍細胞には全く認めず，微小血管とくにendothelial proliferation，あるいはhyperplasiaのみられるものに著明で，血管径が大きくなるに従ってその染色性の分布がせまく，弱まる傾向であった。②免疫電顕法では，悪性，良性ともに血管内皮細胞に陽性で，pericyteには認めず，その他基底膜，血管内腔および血管内腔側内皮細胞膜面に認めた。血管内皮細胞では，endoplasmic reticulum （E．R．），vacuole,vesicle perinuclear spaceに認められた。③悪性腫瘍では，内皮細胞内のF VIII R：Agの分布が良性および非腫瘍脳組織に比較し多く，とくに内皮細胞内E．R．に著明に陽性であることが特徴で，悪性腫瘍血管内皮細胞におけるF VIII R：Agの産生亢進が示唆された。

Using both immunohistochemical and immuno-electron microscopic techniques with periodate-lysine-paraformaldehyde (PLP) fixation, we have studied the distribution of Factor VIII-related antigen (F VIII R : Ag) in 14 cases of human cent-ral nervous system (CNS) tumors and 1 sample of non-tumor brain tissue. F VIII R : Ag was localized to the vascular lumen, to the intercellular spaces between endothelial cells (apparently without tight junctions), and to the endothelial cell basement membrane. In the cytoplasm, F VIII R : Ag was found in the endoplasmic reticulum, perinuclear space, and intracytoplasmic vacuoles and vesiclesonly. Characteristic of malignant tumors (6 out of 7) was strongly-positive dilated endoplasmic reti-culum, whereas only 1 of 5 benign tumors showed such staining. This appears to reflect increased F Vlll R : Ag synthesis in the malignant vessels. The non-tumor brain tissue showed normal capil-lary structure and very little F VIII R : Ag im-munoreactivity. Six of 12 tumors and the non-tumor brain showed perinuclear F VIII R : Ag. Although the basement membranes were more irregular in the malignant tumors, staining was not grossly different from that of the more benign lesions. The finding of both ad-and ablumial vesicles containing F VIII R : Ag suggests that endocytosis, transcellular transport, and/or exo-cytosis, as well as F VIII R : Ag synthesis, occurs in the tumor endothelial cells. The relationship of these F VIII R : Ag abnormalities to the hyper-coagulable state seen in some malignant brain tumor patients remains to be clarified.