Intraocular Medulloepitheliomas and Embryonal Tumors With Multilayered Rosettes of the Brain: Comparative Roles of LIN28A and C19MC.
OBJECTIVE
To compare immunohistochemical and genetic overlaps and differences between intraocular medulloepitheliomas and embryonal tumors with multilayered rosettes of the brain.


METHODS
Retrospective histopathologic, immunohistochemical, and genetic analysis of 20 intraocular medulloepitheliomas.


METHODS
(1) Review of clinical data and hematoxylin-eosin-stained sections with (2) immunohistochemical staining of paraffin sections using a polyclonal antibody against the protein LIN28A, and (3) fluorescence in situ hybridization (FISH) testing for the amplification of the genetic locus 19q13.42 involving the C19MC cluster of miRNA. Ten retinoblastomas served as controls and to determine the specificity of these biomarkers for intraocular medulloepitheliomas.


RESULTS
Nineteen of the 20 intraocular medulloepitheliomas were either diffusely or focally LIN28A positive (weak, moderate, or strong). The most intense positivity correlated with aggressive behavior such as intraocular tissue invasion or extraocular extension. None of the cases studied by FISH harbored an amplicon for C19MC. The 10 retinoblastomas were LIN28A and C19MC negative.


CONCLUSIONS
LIN28A has a putative role in oncogenesis and is found only in embryonic cells and malignancies. Intraocular medulloepitheliomas and embryonal tumors with multilayered rosettes of the brain both display LIN28A positivity. Only the latter, however, display amplification of the 19q13.42 locus involving C19MC, implying that other causative factors are at play in intraocular medulloepitheliomas. More aggressive tumor behavior within the eye can be partially predicted by LIN28A staining intensity.
David G. Cogan Ophthalmic Pathology Laboratory, Massachusetts Eye & Ear Infirmary, Harvard Medical School, Boston, Massachusetts. Electronic address: Fred_Jakobiec@meei.harvard.edu.
Frederick A
FA
Jakobiec
Division of Pediatric Neuro-oncology, German Cancer Research Center (DKFZ), Heidelberg, Germany.
Marcel
M
Kool
David G. Cogan Ophthalmic Pathology Laboratory, Massachusetts Eye & Ear Infirmary, Harvard Medical School, Boston, Massachusetts.
Anna M
AM
Stagner
Division of Pediatric Neuro-oncology, German Cancer Research Center (DKFZ), Heidelberg, Germany; Department of Pediatric Hematology and Oncology, Heidelberg University Hospital, Heidelberg, Germany.
Stefan M
SM
Pfister
Wills Eye Hospital, Thomas Jefferson University, Philadelphia, Pennsylvania.
Ralph C
RC
Eagle
Duke University Department of Pathology, Durham, North Carolina.
Alan D
AD
Proia
Clinical Cooperation Unit Neuropathology, German Cancer Research Center (DKFZ), and Department of Neuropathology, University Hospital, Heidelberg, Germany.
Andrey
A
Korshunov
D000293:Adolescent; D000328:Adult; D014408:Biomarkers, Tumor / Q000235:genetics / Q000378:metabolism; D002648:Child; D002675:Child, Preschool; D002888:Chromosomes, Human, Pair 19 / Q000235:genetics*; D002924:Ciliary Body / Q000473:pathology*; D003937:Diagnosis, Differential; D005260:Female; D005784:Gene Amplification; D006801:Humans; D007124:Immunoenzyme Techniques; D017404:In Situ Hybridization, Fluorescence; D007223:Infant; D008297:Male; D035683:MicroRNAs / Q000235:genetics*; D008875:Middle Aged; D009373:Neoplasms, Germ Cell and Embryonal / Q000175:diagnosis* / Q000235:genetics / Q000378:metabolism; D018242:Neuroectodermal Tumors, Primitive / Q000175:diagnosis* / Q000235:genetics / Q000378:metabolism; D016601:RNA-Binding Proteins / Q000378:metabolism*; D012189:Retrospective Studies; D014604:Uveal Neoplasms / Q000175:diagnosis* / Q000235:genetics / Q000378:metabolism
D014408:Biomarkers, Tumor; C516326:LIN28B protein, human; D035683:MicroRNAs; D016601:RNA-Binding Proteins