Correlation of histology and molecular genetic analysis of 1p, 19q, 10q, TP53, EGFR, CDK4, and CDKN2A in 91 astrocytic and oligodendroglial tumors.

TLDR

The histological diagnosis of human gliomas is subjective and variable, limiting prognostic estimation and therapeutic guidance. The study aimed to determine whether molecular genetic analysis could provide a more objective classification of gliomas and reduce diagnostic variability. The authors performed molecular genetic analysis of 1p, 19q, 10q, TP53, EGFR, and CDK4 abnormalities on 91 nonselected gliomas and compared the results with consensus diagnoses from four neuropathologists. They found that 29 tumors exhibited 1p or 19q loss of heterozygosity with intact 10q, 86 % of which were oligodendroglial types, and that concordant diagnoses were almost exclusive to cases with combined 1p/19q LOH; TP53 mutations were inversely associated with 1p LOH, suggesting 1p LOH and TP53 mutations as markers of oligodendroglial and astrocytic pathways, respectively, and demonstrating that molecular genetic profiling has significant diagnostic value, especially for oligodendroglial tumors.

Abstract

The histological diagnosis of human gliomas is of great importance for estimating patient prognosis and guiding therapy but suffers from being subjective and, therefore, variable. We hypothesized that molecular genetic analysis could provide a more objective means to classify tumors and, thus, reduce diagnostic variability.We performed molecular genetic analysis on 91 nonselected gliomas for 1p, 19q, 10q, TP53, epidermal growth factor receptor, and cyclin-dependent kinase 4 abnormalities and compared with the consensus diagnoses established among four independent neuropathologists.There were six astrocytomas, seven anaplastic astrocytomas, 45 glioblastomas, 21 oligodendrogliomas, eight anaplastic oligodendrogliomas, three oligoastrocytomas, and one anaplastic oligoastrocytoma. Twenty-nine cases had either 1p or 19qloss of heterozygosity (LOH) while retaining both copies of 10q, of which 25 (86%) were histologically oligodendroglioma, anaplastic oligodendroglioma, oligoastrocytoma, or anaplastic oligoastrocytoma. As for the oligodendroglial tumors, unanimous agreement of the initial diagnoses was almost restricted to those cases with combined 1p/19qLOH, whereas all nine tumors without 1p loss initially received variable diagnoses. Interestingly, TP53 mutation was inversely related to 1pLOH in all gliomas (P = 0.0003) but not 19qLOH (P = 0.15).These data demonstrate that molecular genetic analysis of 1p/19q/10q/TP53 has significant diagnostic value, especially in detecting oligodendroglial tumors. In addition, 1pLOH and TP53 mutations in gliomas may be markers of oligodendroglial and astrocytic pathways, respectively, which may separate gliomas with the same histological diagnosis, especially oligodendroglial tumors and glioblastomas. Testing for those molecular genetic alterations would be essential to obtain more homogeneous sets of gliomas for the future clinical studies.