False-positive 1p/19q Testing Results in Gliomas: Clinical and Research Consequences.


Journal

American journal of clinical oncology
ISSN: 1537-453X
Titre abrégé: Am J Clin Oncol
Pays: United States
ID NLM: 8207754

Informations de publication

Date de publication:
11 2020
Historique:
pubmed: 6 9 2020
medline: 2 1 2021
entrez: 5 9 2020
Statut: ppublish

Résumé

The revised fourth edition of the World Health Organization Classification of Tumors of the Central Nervous System-published in 2016-established 1p19q codeletion as the molecular hallmark for the diagnosis of oligodendrogliomas. Fluorescence in situ hybridization (FISH) is currently the most commonly used modality for 1p19q testing. However, as with most laboratory testing, 1p19q FISH testing has a false-positive rate, potentially resulting in an erroneous diagnosis of oligodendroglioma with significant implications for the choice of therapy and prognosis. The authors describe a case series of 5 patients treated at the Ohio State University James Cancer Center to illustrate the problem of false-positive 1p19q FISH results. In our case series, the authors present a spectrum of possibilities for conflicting 1p19q testing results and the clinical consequences. The authors present 4 cases that, in retrospect, are believed to have had a false 1p19q FISH results. One other case may represent a true transformation of oligodendroglioma to glioblastoma or a second malignancy. Neuro-oncologists should pay attention to additional molecular markers, namely ATRX, TP53, and MGMT methylation status, before discussing the pathology with the patient and formulating a treatment plan. Pathologists and neuro-oncologists should be aware of false-positive 1p19q FISH results as they can significantly change treatment and prognosis for glioma patients. Moreover, this issue should be taken into account when designing clinical trials specific to this disease cohort.

Sections du résumé

BACKGROUND
The revised fourth edition of the World Health Organization Classification of Tumors of the Central Nervous System-published in 2016-established 1p19q codeletion as the molecular hallmark for the diagnosis of oligodendrogliomas. Fluorescence in situ hybridization (FISH) is currently the most commonly used modality for 1p19q testing. However, as with most laboratory testing, 1p19q FISH testing has a false-positive rate, potentially resulting in an erroneous diagnosis of oligodendroglioma with significant implications for the choice of therapy and prognosis.
METHODS
The authors describe a case series of 5 patients treated at the Ohio State University James Cancer Center to illustrate the problem of false-positive 1p19q FISH results.
RESULTS
In our case series, the authors present a spectrum of possibilities for conflicting 1p19q testing results and the clinical consequences. The authors present 4 cases that, in retrospect, are believed to have had a false 1p19q FISH results. One other case may represent a true transformation of oligodendroglioma to glioblastoma or a second malignancy. Neuro-oncologists should pay attention to additional molecular markers, namely ATRX, TP53, and MGMT methylation status, before discussing the pathology with the patient and formulating a treatment plan.
CONCLUSIONS
Pathologists and neuro-oncologists should be aware of false-positive 1p19q FISH results as they can significantly change treatment and prognosis for glioma patients. Moreover, this issue should be taken into account when designing clinical trials specific to this disease cohort.

Identifiants

pubmed: 32889892
doi: 10.1097/COC.0000000000000755
pii: 00000421-202011000-00009
doi:

Substances chimiques

Biomarkers, Tumor 0

Types de publication

Case Reports Journal Article

Langues

eng

Sous-ensembles de citation

IM

Pagination

802-805

Références

Louis DN, Perry A, Reifenberger G, et al. The 2016 World Health Organization classification of tumors of the central nervous system: a summary. Acta Neuropathol. 2016;131:803–820.
Eckel-Passow JE, Lachance DH, Molinaro AM, et al. Glioma groups based on 1p/19q, IDH, and TERT promoter mutations in tumors. N Engl J Med. 2015;372:2499–2508.
Cairncross G, Wang M, Shaw E, et al. Phase III trial of chemoradiotherapy for anaplastic oligodendroglioma: long-term results of RTOG 9402. J Clin Oncol. 2013;31:337–343.
van den Bent MJ, Brandes AA, Taphoorn MJ, et al. Adjuvant procarbazine, lomustine, and vincristine chemotherapy in newly diagnosed anaplastic oligodendroglioma: long-term follow-up of EORTC brain tumor group study 26951. J Clin Oncol. 2012;31:344–350.
Nikiforova MN, Hamilton RL. Molecular diagnostics of gliomas. Arch Pathol Lab Med. 2011;135:558–568.
Pinkham MB, Telford N, Whitfield GA, et al. FISHing tips: what every clinician should know about 1p19q analysis in gliomas using fluorescence in situ hybridisation. Clin Oncol. 2015;27:445–453.
van den Bent MJ, Baumert B, Erridge SC, et al. Interim results from the CATNON trial (EORTC study 26053-22054) of treatment with concurrent and adjuvant temozolomide for 1p/19q non-co-deleted anaplastic glioma: a phase 3, randomised, open-label intergroup study. Lancet. 2017;390:1645–1653.
Cancer Genome Atlas Research Network. Comprehensive, integrative genomic analysis of diffuse lower-grade gliomas. N Engl J Med. 2015;372:2481–2498.
Wiestler B, Capper D, Hovestadt V, et al. Assessing CpG island methylator phenotype, 1p/19q codeletion, and MGMT promoter methylation from epigenome-wide data in the biomarker cohort of the NOA-04 trial. Neuro-oncology. 2014;16:1630–1638.
Wiestler B, Capper D, Holland-Letz T, et al. ATRX loss refines the classification of anaplastic gliomas and identifies a subgroup of IDH mutant astrocytic tumors with better prognosis. Acta Neuropathol. 2013;126:443–451.
Louis DN, Giannini C, Capper D, et al. cIMPACT-NOW update 2: diagnostic clarifications for diffuse midline glioma, H3 K27M–mutant and diffuse astrocytoma/anaplastic astrocytoma, IDH-mutant. Acta Neuropathol. 2018;135:639–642.

Auteurs

Iyad Alnahhas (I)

Division of Neuro-Oncology, Department of Neurology, Thomas Jefferson University, Philadelphia, PA.

Appaji Rayi (A)

Department of Neurology, Charleston Area Medical Center, Charleston, WV.

Diana Thomas (D)

Division of Neuropathology, Department of Pathology.

Shirley Ong (S)

Division of Neuro-Oncology, Department of Pathology, The Ohio State University Wexner Medical Center, Columbus, OH.

Pierre Giglio (P)

Division of Neuro-Oncology, Department of Pathology, The Ohio State University Wexner Medical Center, Columbus, OH.

Vinay Puduvalli (V)

Division of Neuro-Oncology, Department of Pathology, The Ohio State University Wexner Medical Center, Columbus, OH.

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