title: A case history of glioma progression.
abstract: Low-grade diffuse astrocytomas have an intrinsic tendency for malignant progression but the factors determining the kinetics of this process are still poorly understood. We report here the case of a male patient who developed a fibrillary astrocytoma at the age of 33 years and who underwent six surgical interventions over a period of 17 years without radiotherapy or chemotherapy. The first three biopsies spanned a period of 11 years and led to the diagnosis of low-grade, diffuse astrocytoma (WHO grade II), with a growth fraction (MIB-1 labeling index) of 2.3-3.7%. The fourth to sixth biopsies showed histological features of anaplastic astrocytoma (WHO grade III), with growth fractions between 5.0 and 10.5%. The fraction of gemistocytic neoplastic astrocytes also increased, from 0.3% in the first biopsy to 17.5% in the last biopsy and preceded the increase in proliferative activity and transition to anaplastic astrocytoma. The fraction of tumor cells immunoreactive to BCL-2 increased from 0.3% to 8.2%. A p53 mutation in codon 273 (CGT-->TGT, Arg-->Cys) was identified in the first biopsy and persisted throughout the course of the disease. However, the fraction of cells with p53 protein accumulation increased significantly during progression, from 3.2% in the first biopsy to 13.7% in the last. The absence of additional genetic alterations (PTEN mutations, loss of chromosome 10 and 19q) may be responsible for the slow progression and lack of glioblastoma features even after a 17-year disease duration.
authors.affiliation: International Agency for Research on Cancer, Lyon, France.
authors.forename: H
authors.initials: H
authors.lastname: Ohgaki
authors.forename: K
authors.initials: K
authors.lastname: Watanabe
authors.forename: A
authors.initials: A
authors.lastname: Peraud
authors.forename: W
authors.initials: W
authors.lastname: Biernat
authors.forename: A
authors.initials: A
authors.lastname: von Deimling
authors.forename: M G
authors.initials: MG
authors.lastname: Yasargil
authors.forename: Y
authors.initials: Y
authors.lastname: Yonekawa
authors.forename: P
authors.initials: P
authors.lastname: Kleihues
mesh_terms: D000328:Adult; D001932:Brain Neoplasms / Q000473:pathology*; D005910:Glioma / Q000473:pathology*; D006801:Humans; D007150:Immunohistochemistry; D008297:Male; D016159:Tumor Suppressor Protein p53 / Q000032:analysis
chemical_list: D016159:Tumor Suppressor Protein p53