J Douglas Cameron1, Fausto J Rodriguez2, Elisabeth Rushing3, Iren Horkayne-Szakaly4, Charles Eberhart5. 1. Departments of Ophthalmology & Visual Neurosciences and Laboratory Medicine & Pathology, University of Minnesota School of Medicine, Minneapolis. 2. Department of Pathology, Division of Neuropathology, and Sidney Kimmel Comprehensive Cancer Center, Johns Hopkins University, Baltimore, Maryland. 3. Department of Pathology, University of Zurich, and Department of Neuropathology, University Hospital Zurich, Switzerland. 4. The Joint Pathology Center, Silver Spring, Maryland. 5. Departments of Pathology, Ophthalmology, and Oncology, Division of Neuropathology, and Sidney Kimmel Comprehensive Cancer Center, Johns Hopkins University, Baltimore, Maryland.
Abstract
PURPOSE: 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.
PURPOSE: 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: Winnie W Pong; Jason Walker; Todd Wylie; Vincent Magrini; Jingqin Luo; Ryan J Emnett; Jaebok Choi; Matthew L Cooper; Malachi Griffith; Obi L Griffith; Joshua B Rubin; Gregory N Fuller; David Piwnica-Worms; Xi Feng; Dolores Hambardzumyan; John F DiPersio; Elaine R Mardis; David H Gutmann Journal: PLoS One Date: 2013-10-11 Impact factor: 3.240