Analysis of the TP53 gene in laser-microdissected glioblastoma vasculature.
Malignant transformation of human gliomas is accompanied by extensive proliferation of stromal blood vessels. Recent data suggest mesenchymal transdifferentiation of neoplastic cells in various human cancers, including colon and breast cancer as well as gliosarcoma. In this study, we have analyzed proliferating stromal blood vessels in glioblastoma multiforme for the presence of mutations in the tumor suppressor gene TP53. Using tissue arrays derived from glioblastoma specimens, cases with significant immunohistochemical p53 accumulation were selected for molecular genetic detection of TP53 mutations in exons 5 to 8. None of the tumors included in this series displayed properties of gliosarcoma. Proliferating glomeruloid stromal vessels were isolated by laser microdissection from paraffin sections. In six cases, single-strand conformation polymorphism analysis for mutations of the TP53 gene in stromal blood vessels compared with adjacent tumor cells and subsequent DNA sequencing of the resulting DNA fragments were carried out. Glioblastoma cells of these cases exhibited TP53 mutations in exons 5, 7 and 8. None of these tumors showed TP53 mutations in microdissected samples from glomeruloid vessels. The absence of TP53 mutations in vascular stromal components of glioblastoma multiforme supports the hypothesis that microvascular proliferations originate from the tumor stroma and are not derived from transdifferentiated glioblastoma cells.
Kulla
Andres
A
Department of Pathology and Neuropathology, Tartu University Clinics, Tartu, Estonia.
Burkhardt
Karim
K
Meyer-Puttlitz
Birgit
B
Teesalu
Tambet
T
Asser
Toomas
T
Wiestler
Otmar D
OD
Becker
Albert J
AJ
D002454:Cell Differentiation; D004252:DNA Mutational Analysis; D004273:DNA, Neoplasm / Q000032:analysis; D004210:Dissection; D016158:Genes, p53 / Q000235:genetics*; D005909:Glioblastoma / Q000098:blood supply* / Q000235:genetics*; D006801:Humans; D007150:Immunohistochemistry; D007834:Lasers; D009154:Mutation; D009389:Neovascularization, Pathologic / Q000235:genetics* / Q000473:pathology*; D020411:Oligonucleotide Array Sequence Analysis; D016133:Polymerase Chain Reaction; D018807:Polymorphism, Single-Stranded Conformational; D017154:Stromal Cells / Q000473:pathology
D004273:DNA, Neoplasm