Histopathological-molecular genetic correlations in referral pathologist-diagnosed low-grade "oligodendroglioma".
Allelic loss of chromosome 1p predicts increased chemosensitivity and better survival in oligodendroglial tumors. Clinical testing for 1p loss in oligodendroglial tumors at our hospital has allowed us to postulate that certain histological appearances are associated with 1p allelic status. Forty-four cases received for genetic testing were diagnosed by referring pathologists as pure low-grade oligodendroglioma. Central neuropathological review divided the series equally into 22 cases with classical oligodendroglioma histology and 22 with more astrocytic features. Molecular genetic analyses demonstrated 1p loss in 19 of 22 classic oligodendrogliomas (86%) and maintenance of both 1p alleles in 16 of 22 gliomas with astrocytic features (73%). No glial fibrillary acidic protein-positive cell type (gliofibrillary oligodendrocyte, minigemistocyte, cellular processes) was associated with 1p allelic status. Fourteen of the 44 cases were treated with chemotherapy at tumor progression: 3 "astrocytic" gliomas with 1p loss responded to PCV chemotherapy and 2 classic oligodendrogliomas that maintained both 1p alleles included a responder and a non-responder. These results suggest that histological appearance correctly predicts genotype in approximately 80% of low-grade gliomas, but that tumor genotype more closely predicts chemosensitivity. As a result, such objective molecular genetic analyses should be incorporated into patient management and into clinical trials of low-grade diffuse gliomas.
Sasaki
Hikaru
H
Department of Pathology and Neurosurgical Service, Massachusetts General Hospital and Harvard Medical School, Boston, USA.
Zlatescu
Magdalena C
MC
Betensky
Rebecca A
RA
Johnk
Loki B
LB
Cutone
Andrea N
AN
Cairncross
J Gregory
JG
Louis
David N
DN
D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use; D001932:Brain Neoplasms / Q000188:drug therapy / Q000235:genetics* / Q000473:pathology* / Q000503:physiopathology; D002878:Chromosomes, Human, Pair 1 / Q000235:genetics; D002945:Cisplatin / Q000627:therapeutic use; D003520:Cyclophosphamide / Q000627:therapeutic use; D005904:Glial Fibrillary Acidic Protein / Q000378:metabolism; D006801:Humans; D007150:Immunohistochemistry; D009457:Neuroglia / Q000378:metabolism / Q000473:pathology; D009837:Oligodendroglioma / Q000188:drug therapy / Q000235:genetics* / Q000473:pathology* / Q000503:physiopathology; D014751:Vindesine / Q000627:therapeutic use
D005904:Glial Fibrillary Acidic Protein; D003520:Cyclophosphamide; D002945:Cisplatin; D014751:Vindesine