Astrocytic tumorにおける血管内皮増生とその基底膜変化—抗laminin抗体を用いた免疫組織化学的検索による検討

MORPHOLOGICAL CHANGES OF BASEMENT MEMBRANE ASSOCIATED WITH ENDOTHELIAL PROLIFERATION IN ASTROCYTIC TUMORS: AN IMMUNOHISTOCHEMICAL STUDY OF LAMININ

　抄録　Glioblastoma （GB）13例，anaplastic astrocytoma （AA）15例，astrocytoma （A）7例，pilocyticastrocytoma （PA）6例の手術時摘出標本を対象とし抗laminin抗体を用いた免疫組織化学的検索を行い，腫瘍血管の内皮増生をその基底膜変化の面より検討した。腫瘍血管の基底膜は内皮増生に伴って解離，肥厚，断裂，屈曲，癒合が強くなり，GBでは特に顕著であった。A,AA,PAではそれぞれの腫瘍内において血管の基底膜変化がほぼ一定しているのに反し，GBでは腫瘍内の部位により基底膜の形態学的変化に著しい違いが見られた。microscopic angiogenesis grading system （MAGS）を用いた内皮増生程度の検討ではglioblastomaが最多得点を示し，GB,AA,Aの間に有意な差が認められた。また，　lanlinin染色標本はMAGSによる内皮増生の評価に非常に適した染色手段と考えられた。

Morphological changes of the basement mem-brane associated with endothelial proliferation in astrocytic tumors are studied in this report. Lami-nin is known to be a specific glycoprotein of base-ment membranes. We applied this characteristic of laminin to enable us to observe various charac-teristics of the basement membrane. The presenceof laminin in 13 glioblastomas, 15 anaplastic astro-cytomas, 7 astrocytomas, and 6 pilocytic astrocy-tomas was examined by peroxidase-antiperoxidase (PAP) staining of formalin-fixed and paraffin-embedded surgical specimens. White matter from five normal cerebral hemispheres obtained during autopsy and subsequently embedded using the same method, were used as a control. Laminin was observed at the glioma-mesenchymal junction in astrocytic tumors, and the deposits of laminin made the tumor vasculature come into intense relief. The destructive changes of the basement membrane, including disruption, thickening, disconnection, dissociation, winding, and conjunction, became greater with progressive endothelial proliferation in astrocytic tumors. Those changes were seen to be most remarkabe in glioblastoma. In addition, there was a marked variety of morphological change in the basement membrane in different areas of glioblastomas, although the changes were almost constant in other astrocytic tumors. We present a schematic hypothesis of the stages of angiogenesis in glioblastoma based on the above morphological changes of the basement membrane and discuss it in this report. In this scheme, the morphological changes of the basement membrane seen in astro-cytoma or anaplastic astrocytoma are considered to correspond to the changes seen in the early stages of angiogenesis in glioblastoma. Furthermore, we estimated the extent of angiogenesis in astrocytic tumor specimens with PAP staining for laminin using the microscopic angiogenesis grading system (MAGS) originally reported by Brem et al.. Glio-blastoma exhibited, by far the highest MAGS score. PAP staining for laminin made it easy to evaluate the MAGS score. Also, it has been suggested that this technique would be a suitable technique not only for observing morphological changes of the basement membrane in vessels, but also for estimat-ing the extent of angiogenesis in astrocytic tumors.