LIN28A immunoreactivity is a potent diagnostic marker of embryonal tumor with multilayered rosettes (ETMR)

Andrey Korshunov, Marina Ryzhova, David T W Jones, Paul A. Northcott, Peter Van Sluis, Richard Volckmann, Jan Koster, Rogier Versteeg, Cynthia Cowdrey, Arie Perry, Daniel Picard, Marc Rosenblum, Felice Giangaspero, Eleonora Aronica, Ulrich Schüller, Martin Hasselblatt, V. Peter Collins, Andreas Von Deimling, Peter Lichter, Annie HuangStefan M. Pfister, Marcel Kool

Research output: Contribution to journalArticle

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.

Original languageEnglish
Pages (from-to)875-881
Number of pages7
JournalActa Neuropathologica
Volume124
Issue number6
DOIs
Publication statusPublished - Dec 2012

Keywords

  • Diagnostic marker
  • ETMR
  • LIN28A
  • Pediatric brain tumor

ASJC Scopus subject areas

  • Clinical Neurology
  • Pathology and Forensic Medicine
  • Cellular and Molecular Neuroscience

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    Korshunov, A., Ryzhova, M., Jones, D. T. W., Northcott, P. A., Van Sluis, P., Volckmann, R., Koster, J., Versteeg, R., Cowdrey, C., Perry, A., Picard, D., Rosenblum, M., Giangaspero, F., Aronica, E., Schüller, U., Hasselblatt, M., Collins, V. P., Von Deimling, A., Lichter, P., ... Kool, M. (2012). LIN28A immunoreactivity is a potent diagnostic marker of embryonal tumor with multilayered rosettes (ETMR). Acta Neuropathologica, 124(6), 875-881. https://doi.org/10.1007/s00401-012-1068-3