Artikel
Chromosomal imbalances in “WHO stable” and “WHO progressive” astrocytomas grade III
Chromosomale Imbalancen in “WHO stabilen” und „WHO progressiven“ Astrozytomen WHO III
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Veröffentlicht: | 8. Mai 2006 |
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Objective: Histopathological classification of astrocytomas at diagnosis does not always reflect the clinical behavior of these nowadays still incurable tumours. This study was set up to analyze the prognostic significance of molecular cytogenetic aberrations in WHO III astrocytomas regarding recurrence and malignant progression.
Methods: Using comparative genomic hybridization (CGH) on formalin-fixed and paraffin-embedded tissue samples, a total of 55 primary WHO III and 32 associated recurrences (17 AIII and 15 secondary GBM) were analyzed. The chromosomal imbalances were correlated with WHO grade (Fisher’s exact test for contingency tables) as well as with overall survival (Mantel-Haenszel log-rank test for censored data).
Results: In primary tumors frequently altered regions (>20%) were gains at 9q and 12p as well as losses at 3p, 6q, 14q, 13q and 15q. Aberrations detected >30% were gains on 7p and 7q as well as losses mapped to 4q, 10p, 10q. In none of the recurrences evolving from the same grade tumor analysis revealed gain of 7p and 7q as well as loss of 10p and 10q, whereas almost 50% of secondary GBM showed alterations at chromosomes 7 and 10, respectively. Over 50% of secondary GBM showed a loss mapped to 13q, whereas -13q was only seen in less than 30% of primary WHO III. Gain of whole chromosome 20 was observed in 43.0% of anaplastic astrocytoma showing malignant progression and never found in “genetic stable” astrocytoma WHO III recurring as same grade tumors. Patients with balanced chromosome 10 age-independently showed a significantly longer over-all survival than patients with monosomy of chromosome 10 (p=0.0007).
Conclusions: Existence of gain of chromosome 7 and/or loss of chromosome 10 seems to be decisive for a high histopathological and as well genetic instability. Moreover, the propensity for losses on chromosome 13q and gains on chromosome 20 in recurrent tumours suggests that these aberrations may play not only a role in tumour recurrence, but also in malignant progression. In addition, losses of 10p and 10q might be independent poor prognostic factors for survival.