title: Molecular diagnosis of orbital inflammatory disease.
abstract: Orbital inflammatory diseases include thyroid eye disease (TED), granulomatosis with polyangiitis (GPA), sarcoidosis, and nonspecific orbital inflammation (NSOI). Histopathological diagnosis usually relies on the clinical context and is not always definitive. Gene expression profiling provides diagnostic and therapeutic information in several malignancies, but its role in evaluating nonmalignant disease is relatively untested. We hypothesized that gene expression profiling could provide diagnostic information for NSOI. We collected formalin-fixed, paraffin-embedded orbital biopsies from 10 institutions and 83 subjects including 25 with thyroid eye disease, 25 nonspecific orbital inflammation, 20 healthy controls, 6 with granulomatosis with polyangiitis, and 7 with sarcoidosis. Tissues were divided into discovery and validation sets. Gene expression was quantified using Affymetrix U133 Plus 2.0 microarrays. A random forest statistical algorithm based on data from 39 probe sets identified controls, GPA, or TED with an average accuracy of 76% (p=0.02). Random forest analysis indicated that 52% of tissues from patients with nonspecific inflammation were consistent with a diagnosis of GPA. Molecular diagnosis by gene expression profiling will augment clinical data and histopathology in differentiating forms of orbital inflammatory disease.
authors.affiliation: Casey Eye Institute, Oregon Health & Science University, Portland, OR 97239, USA; Department of Medicine, Oregon Health & Science University, Portland, OR 97239, USA; Devers Eye Institute, Legacy Health Systems, Portland, OR 97210, USA. Electronic address: rosenbaj@ohsu.edu.
authors.forename: James T
authors.initials: JT
authors.lastname: Rosenbaum
authors.affiliation: Casey Eye Institute, Oregon Health & Science University, Portland, OR 97239, USA; Department of Medicine, Oregon Health & Science University, Portland, OR 97239, USA; Department of Public Health and Preventive Medicine, Oregon Health & Science University, Portland, OR 97239, USA.
authors.forename: Dongseok
authors.initials: D
authors.lastname: Choi
authors.affiliation: Casey Eye Institute, Oregon Health & Science University, Portland, OR 97239, USA.
authors.forename: David J
authors.initials: DJ
authors.lastname: Wilson
authors.affiliation: Integrated Genomics Laboratory, Oregon Health & Science University, Portland, OR 97239, USA.
authors.forename: Hans E
authors.initials: HE
authors.lastname: Grossniklaus
authors.affiliation: Department of Medicine, Oregon Health & Science University, Portland, OR 97239, USA.
authors.forename: Cailin H
authors.initials: CH
authors.lastname: Sibley
authors.affiliation: Integrated Genomics Laboratory, Oregon Health & Science University, Portland, OR 97239, USA.
authors.forename: Christina A
authors.initials: CA
authors.lastname: Harrington
authors.affiliation: Casey Eye Institute, Oregon Health & Science University, Portland, OR 97239, USA; Department of Medicine, Oregon Health & Science University, Portland, OR 97239, USA; Devers Eye Institute, Legacy Health Systems, Portland, OR 97210, USA.
authors.forename: Stephen R
authors.initials: SR
authors.lastname: Planck
mesh_terms: D020869:Gene Expression Profiling; D014890:Granulomatosis with Polyangiitis / Q000175:diagnosis* / Q000235:genetics; D006801:Humans; D025202:Molecular Diagnostic Techniques / Q000379:methods*; D020411:Oligonucleotide Array Sequence Analysis; D009915:Orbit / Q000473:pathology; D016727:Orbital Pseudotumor / Q000175:diagnosis* / Q000235:genetics; D012507:Sarcoidosis / Q000175:diagnosis* / Q000235:genetics
keywords: Gene expression; Granulomatosis with polyangiitis; Orbital inflammation; Sarcoidosis; Thyroid eye disease