Anaplastic human gliomas grown in athymic mice. Morphology and glial fibrillary acidic protein expression.
The morphologic and biochemical characteristics of human surgical biopsy specimens taken from 17 patients with anaplastic human gliomas and of athymic mouse-grown tumors derived from them were examined. Fourteen were categorized as glioblastoma multiforme, one as an anaplastic astrocytoma, one as a recurrent glioblastoma multiforme, and one as a gliosarcoma. Fifteen of 17 tumors stained positively immunohistochemically for glial fibrillary acidic protein (GFAP), a glial-specific marker. When portions of the 17 surgical biopsy specimens were injected into the flank subcutaneous space of athymic mice, 16 produced tumors; different portions of a single biopsy specimen were used to establish three separate tumor lines; in toto, 18 tumor lines were established. Mouse-borne tumors contained various proportions of fibrillary and protoplasmic astrocytes, gemistocytes, small anaplastic cells, and multinucleated giant cells. Some were more homogeneous than the human tumors from which they were derived, while others contained a mixed population similar to that of the original biopsy specimen. Of these initial 18 tumors, 16 were stained for GFAP and 14 contained from fewer than 5% to almost 100% GFAP-expressing cells. Ten of the tumor lines were studied in serial passage, several demonstrating increased cellularity with increased passage. GFAP expression was followed through serial passage, and 7 of 10 tumor lines continued to express it, often in reduced amounts, and 2 of 10 ceased expression, one (the gliosarcoma) never having expressed it. These data demonstrate that while athymic mouse-borne human anaplastic gliomas retained some features of the human tumors from which they were derived, they varied from one another morphologically. These mouse-borne tumors also continued to evolve, often changing their levels of GFAP and demonstrating increased cellularity with passage.