Biologic characterization of a secondary glioblastoma with extracranial progression and systemic metastasis

Abstract

Glioblastomas rarely metastasize outside the CNS. We biologically characterized a case of secondary glioblastoma associated with extracranial progression and distant metastasis. A 42-year-old male patient was subjected to craniotomy for a left temporal tumor (astrocytoma grade II) and subsequently underwent another 3 craniotomies due to tumor recurrences. At the third craniotomy, extracranial progression was noted, and the tumor was classified as a glioblastoma. In order to pinpoint the genes expressed differentially in the intracranial primary tumor and the metastatic tumors, we used cDNA microarray. The patterns of gene expression in these 2 samples were highly similar, suggesting that the mechanism of metastasis was direct infiltration of tumor cells into extracranial blood vessels. Insulin-like growth factor binding protein-2 was overexpressed in both primary and metastatic tumors. Immunohistochemical studies of DNA-dependent protein kinase, which participates in the repair of DNA, was strongly positive in the samples obtained at the first and second operations, but the positive rates were markedly reduced in the specimens obtained at the third and fourth operations. These results suggest that insulin-like growth factor binding protein-2 and deficiency of DNA-dependent protein kinase proteins promoted tumor progression in the present case.

Extra-Neural Metastases of Malignant Gliomas: Myth or Reality?

“…Ueda et al reported a case of secondary GBM associated with a distant ENM [101]. They carried out a cDNA microarray analysis on both the primary and metastatic tumor (cervical lymph node) and found that IGFBP2 (insulin-like growth factor binding protein-2) was overexpressed in both tumor specimens.…”

“…They carried out a cDNA microarray analysis on both the primary and metastatic tumor (cervical lymph node) and found that IGFBP2 (insulin-like growth factor binding protein-2) was overexpressed in both tumor specimens. DNA-dependent protein kinase (DNA-PK), involved in DNA repair mechanisms, was strongly positive for the first and second operative tumor, and the positive rate decreased in tumor specimens from third and fourth operations [101]. They purport that IGFBP2 probably plays a role in GBM tumor progression, and DNA-PK in the malignant transformation of glioma [101].…”

“…DNA-dependent protein kinase (DNA-PK), involved in DNA repair mechanisms, was strongly positive for the first and second operative tumor, and the positive rate decreased in tumor specimens from third and fourth operations [101]. They purport that IGFBP2 probably plays a role in GBM tumor progression, and DNA-PK in the malignant transformation of glioma [101]. A similar pattern of genetic expression was found in the primary and metastatic tumor specimens suggesting that the mechanism of distant ENM was probably due to direct extra-cranial infiltration from the tumor into blood vessels [101].…”

“…They purport that IGFBP2 probably plays a role in GBM tumor progression, and DNA-PK in the malignant transformation of glioma [101]. A similar pattern of genetic expression was found in the primary and metastatic tumor specimens suggesting that the mechanism of distant ENM was probably due to direct extra-cranial infiltration from the tumor into blood vessels [101]. …”

Multiple extraneural metastasis of glioblastoma multiforme

“…Several studies using de cDNA microarray technique have showed common findings, such as overexpression of the insulin growth factor and a decrease of DNA-PK genetic expression, which is involved in DNA repair mechanisms. The former is probably related to tumor progression, while the later plays a role in malignant transformation of glioma 16 . As treatment for GBM improves patient survival, incidence of extraneural metastases may continue to increase.…”