
<ArticleTitle><prot><prot>Insulin</prot>-like growth factor-1</prot> content and pattern of expression correlates with histopathologic grade in diffusely infiltrating astrocytomas.</ArticleTitle>
<AbstractText>Studies of experimental tumorigenesis have strongly implicated signaling of the <prot><prot>insulin</prot>-like growth factor 1</prot> (<prot>IGF-1</prot>) as a key component in astrocytic neoplasia; however, its role in the growth of low-grade and malignant human tumors is not well understood. Correlative analyses of <prot>IGF-1</prot>, <prot>p53</prot>, and <prot>Ki-67</prot> (<prot>MIB-1</prot>) immunohistochemistry and <prot><prot>IGF-1</prot> receptor</prot> (<prot>IGF-1R</prot>) mRNA expression were performed to examine the cellular pattern of <prot>IGF-1</prot> signaling in 39 cases of astrocytoma (World Health Organization grades II-IV). Tumor cells expressing <prot>IGF-1</prot> and <prot>IGF-1R</prot> were present in all tumor grades. The proportion of tumor cells that expressed <prot>IGF-1</prot> correlated with both histopathologic grade and <prot>Ki-67</prot> labeling indices, while expression of <prot>IGF-1R</prot> mRNA correlated with <prot>Ki-67</prot> indices. In cases where stereotactic tissue sampling could be identified with a specific tumor area by neuroimaging features, the numbers of <prot>IGF-1</prot> immunoreactive cells correlated with the tumor zones of highest cellularity and <prot>Ki-67</prot> labeling. In glioblastomas, the localization of <prot>IGF-1</prot> immunoreactivity was notable for several features: frequent accentuation in the perivascular tumor cells surrounding microvascular hyperplasia; increased levels in reactive astrocytes at the margins of tumor infiltration; and selective expression in microvascular cells exhibiting endothelial/pericytic hyperplasia. <prot>IGF-1R</prot> expression was particularly prominent in tumor cells adjacent to both microvascular hyperplasia and palisading necrosis. These data suggest that <prot>IGF-1</prot> signaling occurs early in astroglial tumorigenesis in the setting of cell proliferation. The distinctive correlative patterns of <prot>IGF-1</prot> and <prot>IGF-1R</prot> expression in glioblastomas also suggest that <prot>IGF-1</prot> signaling has an association with the development of malignant phenotypes related to aberrant angiogenesis and invasive tumor interactions with reactive brain.</AbstractText>
