Immunohistochemical Profiling of Interferon-Stimulated Genes in Histopathological Specimens: A Potential Screening Approach for Viral Infections

Thomsen C, Birkelund S, Røge R. Immunohistochemical profiling of interferon-stimulated genes in histopathological specimens: A potential screening approach for viral infections. Identifying viral infections in histopathological specimens can pose a diagnostic challenge. Increased expression of interferon-stimulated genes (ISGs) may serve as a potential screening marker for such infections. This study undertakes a comparative analysis of ISG immunohistochemical expression in various tissue types, encompassing both normal and inflamed tissues, including both viral and nonviral etiologies. Archival formalin-fixed paraffin-embedded (FFPE) tissues with confirmed viral infection (n = 27) and nonviral inflammation (n = 15) were analyzed. Tissue microarrays (TMAs) were constructed and stained with antibodies against ISGs: Human myxovirus resistance protein 1 (MxA), RIG-I, MDA5, PKR, and PD-L1. Qualitative assessment compared their upregulation to five normal controls of each tissue type. MxA exhibited significantly increased upregulation in viral infections compared to nonviral inflammation (OR 6.53 [CI 1.59, 26.79]), with sensitivity and specificity of 0.70 (0.50, 0.86) and 0.73 (0.45, 0.92), respectively. The remaining ISGs showed no significant differences and had moderate sensitivity and low specificity. In conclusion, while MxA, PD-L1, PKR, MDA5, and RIG-I generally showed upregulation in most viral infections, variability was observed. MxA holds promise as a viral infection screening marker in FFPE samples, but its utility may be limited by an inadequate interferon response to certain viruses.