Evidence map›Paper›PMID 40839307›Full record

ArticleVirchows Archiv : an international journal of pathology2026

Definition of parameters and thresholds to detect MYCN amplification in retinoblastomas.

C Bielefeld, T Hugo, N Sievers, P Ketteler, E Biewald, T Kiefer, K Papaioannou, P Tüller, T Ryl, M Busch and 3 more

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Article in Virchows Archiv : an international journal of pathology, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.

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1 · What the graph read from it

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3 · Its place in the literature

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4 · The record

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5 · Who and what money

Authors and funding

13 authors.

C BielefeldReference Pathology for Pediatric Eye Tumors, Kassel, Germany. bielefeld@patho-nordhessen.de.
T HugoInstitute of Pathology Nordhessen, Germaniastrasse 7, 34119, Kassel, Germany.
N SieversInstitute of Pathology Nordhessen, Germaniastrasse 7, 34119, Kassel, Germany.
P KettelerGerman Consortium for Translational Cancer Research (DKTK), Essen, Germany.
E BiewaldDepartment of Ophthalmology, University Hospital Essen, University of Duisburg Essen, Essen, Germany.
T KieferDepartment of Ophthalmology, University Hospital Essen, University of Duisburg Essen, Essen, Germany.
K PapaioannouDepartment of Pediatrics 3, University Hospital Essen, University of Duisburg Essen, Essen, Germany.
P TüllerDepartment of Pediatrics 3, University Hospital Essen, University of Duisburg Essen, Essen, Germany.
T RylDepartment of Pediatrics 3, University Hospital Essen, University of Duisburg Essen, Essen, Germany.
M BuschInstitute for Anatomy II, Department of Neuroanatomy, Medical Faculty, Center for Translational Neuro- and Behavioral Sciences (C-TNBS), University of Duisburg-Essen, Essen, Germany.
J RawitzerInstitute of Pathology, University of Duisburg-Essen, University Hospital Essen, Essen, Germany.
H-U SchildhausInstitute of Pathology Nordhessen, Germaniastrasse 7, 34119, Kassel, Germany.
S TingReference Pathology for Pediatric Eye Tumors, Kassel, Germany.

Funding

Deutsche Kinderkrebsstiftung DKS2020.14Deutsche Kinderkrebsstiftung DKS2024.08
6 · The paper itself

Abstract

Retinoblastoma is a malignant childhood neoplasm where MYCN amplification defines a subset of tumors with worse prognosis. FISH (fluorescence in situ hybridization) represents a fast and reliable method to measure gene copy numbers in various tumors but has not yet been systematically evaluated in retinoblastoma. In this study, we define criteria for FISH detection of MYCN amplification in a systematic unbiased approach by using a well characterized series of 44 clinical retinoblastoma samples. We (i) determined potential measurements and parameters by a comprehensive literature review, (ii) analyzed a retrospective cohort of samples with known MYCN amplification, (iii) determined statistically measurements and cut-offs, which allow reliable detection of amplified tumors, and (iv) applied these criteria to a prospective cohort. We demonstrate that average gene copy number (AVGCN) of MYCN/cell, MYCN/CEN2 ratio, and MYCN-CEN2 difference reveal the lowest statistical variance in amplified samples, if at least 50 cells were counted. The combination of these three parameters and cut-offs, namely AVGCN ≥ 10, MYCN/CEN2 ratio ≥ 3, and MYCN-CEN2 difference ≥ 8, allowed a reliable distinction between amplified and non-amplified cases. The prevalence of MYCN-amplified cases was 4/33 (12.1%) among prospective clinical samples indicating a higher percentage of positive tumors than previously reported. Our data provide the first evidence for well-grounded MYCN FISH criteria in retinoblastoma.

Indexed as

Biomarkers, TumorGene AmplificationIn Situ Hybridization, FluorescenceN-Myc Proto-Oncogene ProteinRetinal NeoplasmsRetinoblastomaChild, PreschoolFemaleGene DosageHumansInfantMaleRetrospective StudiesBiomarkers, TumorMYCN protein, humanN-Myc Proto-Oncogene ProteinFISHMYCN amplificationOphthalmic pathologyPrognostic biomarkerRetinoblastoma

Identifiers

PMID40839307
PMCPMC13477454

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