LIN28A immunoreactivity is a potent diagnostic marker of embryonal tumor with multilayered rosettes (ETMR)
Open Access
- 16 November 2012
- journal article
- research article
- Published by Springer Science and Business Media LLC in Acta Neuropathologica
- Vol. 124 (6), 875-881
- https://doi.org/10.1007/s00401-012-1068-3
Abstract
Embryonal tumor with multilayered rosettes (ETMR, previously known as ETANTR) is a highly aggressive embryonal CNS tumor, which almost exclusively affects infants and is associated with a dismal prognosis. Accurate diagnosis is of critical clinical importance because of its poor response to current treatment protocols and its distinct biology. Amplification of the miRNA cluster at 19q13.42 has been identified previously as a genetic hallmark for ETMR, but an immunohistochemistry-based assay for clinical routine diagnostics [such as INI-1 for atypical teratoid rhabdoid tumor (AT/RT)] is still lacking. In this study, we screened for an ETMR-specific marker using a gene-expression profiling dataset of more than 1,400 brain tumors and identified LIN28A as a highly specific marker for ETMR. The encoded protein binds small RNA and has been implicated in stem cell pluripotency, metabolism and tumorigenesis. Using an LIN28A specific antibody, we carried out immunohistochemical analysis of LIN28A in more than 800 childhood brain-tumor samples and confirmed its high specificity for ETMR. Strong LIN28A immunoexpression was found in all 37 ETMR samples tested, whereas focal reactivity was only present in a small (6/50) proportion of AT/RT samples. All other pediatric brain tumors were completely LIN28A-negative. In summary, we established LIN28A immunohistochemistry as a highly sensitive and specific, rapid, inexpensive diagnostic tool for routine pathological verification of ETMR.Keywords
This publication has 25 references indexed in Scilit:
- Frequent Amplification of a chr19q13.41 MicroRNA Polycistron in Aggressive Primitive Neuroectodermal Brain TumorsCancer Cell, 2009
- Ependymoblastoma: Dear, Damned, Distracting Diagnosis, Farewell!*Brain Pathology, 2009
- Intrinsic Gene Expression Profiles of Gliomas Are a Better Predictor of Survival than HistologyCancer Research, 2009
- Embryonal Tumors With Abundant Neuropil and True RosettesThe American Journal of Surgical Pathology, 2009
- Beta‐catenin status in paediatric medulloblastomas: correlation of immunohistochemical expression with mutational status, genetic profiles, and clinical characteristicsThe Journal of Pathology, 2009
- Integrated Genomics Identifies Five Medulloblastoma Subtypes with Distinct Genetic Profiles, Pathway Signatures and Clinicopathological FeaturesPLOS ONE, 2008
- Selective Blockade of MicroRNA Processing by Lin28Science, 2008
- The 2007 WHO Classification of Tumours of the Central Nervous SystemActa Neuropathologica, 2007
- Neuronal and glioma-derived stem cell factor induces angiogenesis within the brainCancer Cell, 2006
- Gene expression analyses reveal molecular relationships among 20 regions of the human CNSneurogenetics, 2006