[Frontiers in Bioscience 8, a1-9, January 1, 2003]

ANCILLARY FISH ANALYSIS FOR 1p AND 19q STATUS: PRELIMINARY OBSERVATIONS IN 287 GLIOMAS AND OLIGODENDROGLIOMA MIMICS

Arie Perry 1, Christine E. Fuller 1, Ruma Banerjee 1, Daniel J. Brat 2, Bernd W. Scheithauer 3

1 Divisions of Neuropathology, Washington University School of Medicine, St. Louis, MO, 2 Emory Univ. Hospital, Atlanta, GA, and 3 Mayo Clinic, Rochester, MN

TABLE OF CONTENTS

1. Abstract
2. Introduction
3. Materials and Methods
3.1. Patient and tumor cohort
3.2. Fluorescence in situ hybridization (FISH)
4. Results and Discussion
4.1. Technical considerations and 1p/19q FISH patterns in diffuse gliomas
4.2. "Oligodendroglioma mimics" and specificity of deletions
4.3. Clinical followup and associations with survival time
4.4. Other potentially useful genetic markers
5. Summary
6. Acknowledgements
7. References

1. ABSTRACT

Deletions of chromosomes 1p and 19q are associated with chemosensitivity and enhanced survival in oligodendrogliomas. Therefore, we have utilized FISH analysis as an ancillary tool for diffuse gliomas with suspected oligodendroglial features. To date, 246 gliomas have been analyzed in 131 male and 93 female patients, including 109 oligodendrogliomas (O), 109 mixed oligoastrocytomas / equivocal gliomas (MOA), and 28 astrocytomas (A). To address specificity, we also analyzed 41 oligodendroglioma mimics, including 12 central and 12 extraventricular neurocytomas (EVN), 12 dysembryoplastic neuroepithelial tumors, and 5 clear cell ependymomas. Aside from 2 EVNs, no mimics demonstrated codeletion. Three patterns were associated with glioma cell type (O vs. MOA/A): -1p/19q, -19q alone, and polysomies. Long-term survivals of >5-years (N=47) and >10-years (N=16) were associated with 1p/19q codeletion in 60% and 75% respectively, whereas solitary 19q deletion accounted for 11% and 6% respectively. Survivals <2-years (N=10) were associated with lack of deletions in 70%. A few older patients with high-grade, "genetically favorable" tumors did poorly, whereas prolonged survival was observed in several low-grade glioma patients despite a lack of the "genetically favorable" pattern. Our data suggests that: 1) FISH-detectable 1p/19q codeletion is relatively specific for oligodendrogliomas with long survival, 2) solitary 19q deletion may also portend a favorable prognosis in a smaller subset, and 3) combined clinicopathologic and genetic assessment likely provides a more accurate means of patient stratification than either one alone.