Frequency of false-positive FISH 1p/19q codeletion in adult diffuse astrocytic gliomas

• Published in: Neuro-oncology advances 2020-01, Vol.2 (1), p.vdaa109-vdaa109
• Main Authors: Ball, Matthew K, Kollmeyer, Thomas M, Praska, Corinne E, McKenna, Michelle L, Giannini, Caterina, Raghunathan, Aditya, Jentoft, Mark E, Lachance, Daniel H, Kipp, Benjamin R, Jenkins, Robert B, Ida, Cristiane M
• Format: Article
• Language: English
• Subjects: Basic and Translational Investigations
• ISSN: 2632-2498; 2632-2498
• DOI: 10.1093/noajnl/vdaa109

Abstract Background Oligodendroglioma is genetically defined by concomitant IDH (IDH1/IDH2) mutation and whole-arm 1p/19q codeletion. Codeletion of 1p/19q traditionally evaluated by fluorescence in situ hybridization (FISH) cannot distinguish partial from whole-arm 1p/19q codeletion. Partial 1p/19q codeletion called positive by FISH is diagnostically a “false-positive” result. Chromosomal microarray (CMA) discriminates partial from whole-arm 1p/19q codeletion. Herein, we aimed to estimate the frequency of partial 1p/19q codeletion that would lead to a false-positive FISH result. Methods FISH 1p/19q codeletion test probe coordinates were mapped onto Oncoscan CMA data to determine the rate of partial 1p/19q codeletion predicted to be positive by FISH. Diffuse astrocytic gliomas with available CMA data (2015–2018) were evaluated and classified based on IDH1-R132H/ATRX/p53 immunohistochemistry, IDH/TERT promoter targeted sequencing, and/or CMA according to classification updates. Predicted false-positive cases were verified by FISH whenever possible. Results The overall estimated false-positive FISH 1p/19q codeletion rate was 3.6% (8/223). Predicted false positives were verified by FISH in 6 (of 8) cases. False-positive rates did not differ significantly (P = .49) between IDH-mutant (4.6%; 4/86) and IDH-wildtype (2.9%; 4/137) tumors. IDH-wildtype false positives were all WHO grade IV, whereas IDH-mutant false positives spanned WHO grades II-IV. Testing for 1p/19q codeletion would not have been indicated for most false positives based on current classification recommendations. Conclusion Selective 1p/19q codeletion testing and cautious interpretation for conflicting FISH and histopathological findings are recommended to avoid potential misdiagnosis.