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Correlation of Histology and Molecular Genetic Analysis of 1p, 19q, 10q, TP53, EGFR, CDK4, and CDKN2A in 91 Astrocytic and Oligodendroglial Tumors¹

Department of Neurosurgery, University of Tokyo Hospital, Tokyo 113-8655 [K. U., A. M., A. A., T. K.]; Departments of Neurosurgery [R. N.] and Pathology [T. H.], Saitama Medical School Saitama 350-0495; First Department of Pathology, Gunma University Medical School [Y. N., J. H.] Maebashi 371-0034; Department of Pathology, Tokyo Metropolitan Komagome Hospital [N. F.] Tokyo 113-8677; Departments of Neurosurgery, Teikyo University Hospital [T. F., S. H.] Tokyo 173-8605; Tokyo Women’s Medical University [O. K.] Tokyo 162-8666; Tokyo Metropolitan Bokuto Hospital [T. I.] Tokyo 130-8575; Toranomon Hospital [M. U.] Tokyo 105-8470; Kanto Medical Center NTT-East [C. O.] Tokyo 141-0022; Tokyo Teishin Hospital [S. I.] Tokyo 102-8798; Tokyo Metropolitan Neurological Institute [H. T.] Tokyo 183-0042; and Core Research for Evolutional Science and Technology, Kawaguchi 332-0012 [T. K.], Japan

Purpose: 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.

Experimental Design: 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.

Results: 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).

Conclusions: 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.

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