Reclassification of oligoastrocytomas by loss of heterozygosity studies.
Oligoastrocytomas (OAs) are WHO grade II or III tumors composed of a mixture of 2 neoplastic cell types morphologically resembling the cells in oligodendrogliomas and diffuse astrocytomas. Investigations on the genetic profile of OAs may yield important information for their classification and help for their clinical management. We have studied, in 94 OAs (46 WHO grade II and 48 WHO grade III), the patterns of loss of heterozygosity (LOH) of 4 genomic regions: 1p, 19q, 17p and 10q. Results were as follows: LOH 1p was present in 46% of the tumors; LOH 19q in 45%; LOH 17p in 22%; LOH 10q in 16%. LOH 1p and 19q were associated in 32%, other LOH associations were rare (<3%). Patients had a median follow-up of 30 months. Patients without LOH on 1p had shorter progression free survival than patients with LOH on 1p: 30 vs. 132 months, p < 0.0001. MRI indicated that tumors without LOH on 1p were often temporal (p < 0.02), and showed signal inhomogeneity on T1 and T2 images (p < 0.02) and contrast enhancement (p < 0.04). Thus, LOH on 1p identifies two subgroups of OAs. OAs without LOH on 1p behave like WHO grade II or III diffuse astrocytomas: they have shorter survival, MRI characteristics implying malignancy and genetic alterations associated with tumor progression. OAs with LOH on 1p, on the other hand, behave like WHO grade II or III oligodendrogliomas with 1p loss: they are associated with longer survival and do not have MRI or genetic alterations associated with malignancy. These findings suggest that the definition of OAs or mixed gliomas could be reshaped in agreement with the genetic information.
Eoli
Marica
M
Department of Clinical Neurosciences, Istituto Nazionale Neurologico Besta, Milan, Italy.
Bissola
Lorena
L
Bruzzone
Maria Grazia
MG
Pollo
Bianca
B
Maccagnano
Carmelo
C
De Simone
Tiziana
T
Valletta
Lorella
L
Silvani
Antonio
A
Bianchessi
D
D
Broggi
Giovanni
G
Boiardi
Amerigo
A
Finocchiaro
Gaetano
G
D000328:Adult; D000704:Analysis of Variance; D001254:Astrocytoma / Q000145:classification* / Q000235:genetics* / Q000473:pathology / Q000601:surgery; D001932:Brain Neoplasms / Q000145:classification* / Q000235:genetics* / Q000473:pathology / Q000601:surgery; D002878:Chromosomes, Human, Pair 1; D002879:Chromosomes, Human, Pair 10; D002886:Chromosomes, Human, Pair 17; D002888:Chromosomes, Human, Pair 19; D018450:Disease Progression; D018572:Disease-Free Survival; D005260:Female; D006801:Humans; D019656:Loss of Heterozygosity; D008279:Magnetic Resonance Imaging; D008297:Male; D008875:Middle Aged; D016019:Survival Analysis