Molecular diagnosis of orbital inflammatory disease

• Published in: Experimental and molecular pathology Vol. 98; no. 2; pp. 225 - 229
• Main Authors: Rosenbaum, James T., Choi, Dongseok, Wilson, David J., Grossniklaus, Hans E., Sibley, Cailin H., Harrington, Christina A., Planck, Stephen R.
• Format: Journal Article
• Language: English
• Published: Netherlands Elsevier Inc 01.04.2015
• Subjects: Gene expression; Gene Expression Profiling; Granulomatosis with polyangiitis; Granulomatosis with Polyangiitis - diagnosis; Granulomatosis with Polyangiitis - genetics; Humans; Molecular Diagnostic Techniques - methods; Oligonucleotide Array Sequence Analysis; Orbit - pathology; Orbital inflammation; Orbital Pseudotumor - diagnosis; Orbital Pseudotumor - genetics; Sarcoidosis; Sarcoidosis - diagnosis; Sarcoidosis - genetics; Thyroid eye disease; TED; Sarcoidosis; Thyroid eye disease; Orbital inflammation; Granulomatosis with polyangiitis; GPA; NSOI; Gene expression
• ISSN: 0014-4800; 1096-0945; 1096-0945
• DOI: 10.1016/j.yexmp.2015.01.009

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. •Orbital inflammation has a broad differential diagnosis.•An international team quantified specific RNA transcripts in orbital biopsies.•This information enhanced the diagnostic accuracy of biopsies.