title: An 80-year experience with optic nerve glioma cases at the Armed Forces Institute of Pathology: evolution from museum to molecular evaluation suggests possibe interventions in the cellular senescence and microglial pathways (an American Ophthalmological Society thesis).
abstract: OBJECTIVE
  To determine whether p16, a molecular marker of cellular senescence, and CD68, a microglial marker, are detectible in optic nerve glioma tissue stored for decades, thus providing potential targets for pharmacologic intervention.
  
  
  METHODS
  Cases were retrieved from the Armed Forces Institute of Pathology Registry of Ophthalmic Pathology. Clinical information was tabulated. In specimens with sufficient tissue, a tissue microarray was constructed to conduct molecular studies.
  
  
  RESULTS
  Ninety-two cases were included: gender distribution was in a ratio of one male to 1.6 females, and age range was 2 months to 50 years (average age, 10.8 years). Neurofibromatosis type 1 was identified in 10 cases (10.8%). The majority presented with decreased vision and exophthalmos. Forty-eight cases were studied by a tissue microarray construction. Glial fibrillary acidic protein, a control for immunoreactivity, was positive in 46 cases (96%). Immunoreactivity for p16 protein was seen in 36 cases (75%) and CD68-positive cells in 34 (71%). Limitations include referral bias, limited clinical information, limited amount of tissue, and extended period of tissue preservation.
  
  
  CONCLUSIONS
  Optic nerve glioma is a tumor of the visual axis in young individuals, which is generally indolent but with a variable clinical course. Traditional histopathologic techniques have not been reliably predictive of clinical course. This microarray contains tumors with representative demographic, clinical, and histologic characteristics for optic nerve glioma. Immunoreactivity for p16 protein and CD68 is positive in the majority. These findings suggest a possible explanation for the variable clinical course and identify therapeutic targets in the cell senescence and microglial pathways.
authors.affiliation: Departments of Ophthalmology & Visual Neurosciences and Laboratory Medicine & Pathology, University of Minnesota School of Medicine, Minneapolis.
authors.forename: J Douglas
authors.initials: JD
authors.lastname: Cameron
authors.affiliation: Department of Pathology, Division of Neuropathology, and Sidney Kimmel Comprehensive Cancer Center, Johns Hopkins University, Baltimore, Maryland.
authors.forename: Fausto J
authors.initials: FJ
authors.lastname: Rodriguez
authors.affiliation: Department of Pathology, University of Zurich, and Department of Neuropathology, University Hospital Zurich, Switzerland.
authors.forename: Elisabeth
authors.initials: E
authors.lastname: Rushing
authors.affiliation: The Joint Pathology Center, Silver Spring, Maryland.
authors.forename: Iren
authors.initials: I
authors.lastname: Horkayne-Szakaly
authors.affiliation: Departments of Pathology, Ophthalmology, and Oncology, Division of Neuropathology, and Sidney Kimmel Comprehensive Cancer Center, Johns Hopkins University, Baltimore, Maryland.
authors.forename: Charles
authors.initials: C
authors.lastname: Eberhart
mesh_terms: D000293:Adolescent; D000328:Adult; D015703:Antigens, CD / Q000032:analysis*; D015214:Antigens, Differentiation, Myelomonocytic / Q000032:analysis*; D014408:Biomarkers, Tumor / Q000032:analysis*; D002648:Child; D002675:Child, Preschool; D019941:Cyclin-Dependent Kinase Inhibitor p16 / Q000032:analysis*; D005260:Female; D006801:Humans; D007223:Infant; D008297:Male; D008875:Middle Aged; D020339:Optic Nerve Glioma / Q000737:chemistry*; D012189:Retrospective Studies; D013048:Specimen Handling; D013997:Time Factors; D046888:Tissue Array Analysis; D014021:Tissue Preservation; D055815:Young Adult; D000097382:CD68 Molecule
chemical_list: D015703:Antigens, CD; D015214:Antigens, Differentiation, Myelomonocytic; D014408:Biomarkers, Tumor; D019941:Cyclin-Dependent Kinase Inhibitor p16; C067980:CD68 antigen, human; D000097382:CD68 Molecule