Organotypic distribution of stem cell markers in formalin-fixed brain harboring glioblastoma multiforme

Abstract

The role of stem cells in the origin, growth patterns, and infiltration of glioblastoma multiforme is a subject of intense investigation. One possibility is that glioblastoma may arise from transformed stem cells in the ventricular zone. To explore this hypothesis, we examined the distribution of two stem cell markers, activating transcription factor 5 (ATF5) and CD133, in an autopsy brain specimen from an individual with glioblastoma multiforme. A 41-year-old male with a right posterior temporal glioblastoma had undergone surgery, radiation, and chemotherapy. The brain was harvested within several hours after death. After formalin fixation, sectioning, and mapping of tumor location in the gross specimen, histologic specimens were prepared from tumor-bearing and grossly normal hemispheres. Fluorescence immunohistochemistry and colorimetric staining were performed for ATF5 and CD133. Both markers co-localized to the ependymal and subependymal zones on the side of the tumor, but not in the normal hemisphere or more rostrally in the affected hemisphere. ATF5 staining was especially robust within the diseased hemisphere in histologically normal ependyma. To our knowledge, this is the first in situ demonstration of stem cell markers in whole human brain. These preliminary results support the hypothesis that some glioblastomas may arise from the neurogenic zone of the lateral ventricle. The robust staining for ATF5 and CD133 in histologically normal ventricular zone suggests that an increase in periventricular stem cell activity occurred in this patient on the side of the tumor, either as a localized response to brain injury or as an integral component of oncogenesis and tumor recurrence.