title: LIN28A immunoreactivity is a potent diagnostic marker of embryonal tumor with multilayered rosettes (ETMR).
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.
authors.affiliation: Clinical Cooperation Unit Neuropathology, German Cancer Research Center (DKFZ), Heidelberg, Germany.
authors.forename: Andrey
authors.initials: A
authors.lastname: Korshunov
authors.forename: Marina
authors.initials: M
authors.lastname: Ryzhova
authors.forename: David T W
authors.initials: DT
authors.lastname: Jones
authors.forename: Paul A
authors.initials: PA
authors.lastname: Northcott
authors.forename: Peter
authors.initials: P
authors.lastname: van Sluis
authors.forename: Richard
authors.initials: R
authors.lastname: Volckmann
authors.forename: Jan
authors.initials: J
authors.lastname: Koster
authors.forename: Rogier
authors.initials: R
authors.lastname: Versteeg
authors.forename: Cynthia
authors.initials: C
authors.lastname: Cowdrey
authors.forename: Arie
authors.initials: A
authors.lastname: Perry
authors.forename: Daniel
authors.initials: D
authors.lastname: Picard
authors.forename: Marc
authors.initials: M
authors.lastname: Rosenblum
authors.forename: Felice
authors.initials: F
authors.lastname: Giangaspero
authors.forename: Eleonora
authors.initials: E
authors.lastname: Aronica
authors.forename: Ulrich
authors.initials: U
authors.lastname: Schüller
authors.forename: Martin
authors.initials: M
authors.lastname: Hasselblatt
authors.forename: V Peter
authors.initials: VP
authors.lastname: Collins
authors.forename: Andreas
authors.initials: A
authors.lastname: von Deimling
authors.forename: Peter
authors.initials: P
authors.lastname: Lichter
authors.forename: Annie
authors.initials: A
authors.lastname: Huang
authors.forename: Stefan M
authors.initials: SM
authors.lastname: Pfister
authors.forename: Marcel
authors.initials: M
authors.lastname: Kool
mesh_terms: D000293:Adolescent; D014408:Biomarkers, Tumor / Q000235:genetics*; D001932:Brain Neoplasms / Q000235:genetics* / Q000473:pathology; D002648:Child; D002675:Child, Preschool; D004268:DNA-Binding Proteins / Q000235:genetics*; D003937:Diagnosis, Differential; D020869:Gene Expression Profiling / Q000379:methods; D006801:Humans; D035683:MicroRNAs / Q000235:genetics; D009373:Neoplasms, Germ Cell and Embryonal / Q000235:genetics* / Q000473:pathology; D018242:Neuroectodermal Tumors, Primitive / Q000235:genetics / Q000473:pathology; D019581:Neuropil / Q000378:metabolism* / Q000473:pathology; D016601:RNA-Binding Proteins; D018335:Rhabdoid Tumor / Q000235:genetics / Q000473:pathology
chemical_list: D014408:Biomarkers, Tumor; D004268:DNA-Binding Proteins; C516326:LIN28B protein, human; D035683:MicroRNAs; D016601:RNA-Binding Proteins