Gene expression based molecular test proves clinical validity as diagnostic aid for the differential diagnosis of psoriasis and eczema in formalin fixed and paraffin embedded tissue

Abstract

AbstractHighly specific and efficient drugs have been developed during the last two decades to treat non-communicable chronic inflammatory skin diseases (ncISD). Due to their specificity, these drugs are asking for precise diagnostic measures to attribute the most efficient treatment to each patient. Diagnosis, however, is complicated by the complex pathogenesis of ncISD and their clinical and histological overlap. Especially, precise diagnosis of psoriasis and eczema is difficult in special cases and molecular diagnostic tools need to be developed to support gold standard diagnosis of patients. In this line, we have developed a real-time based molecular classifier to distinguish psoriasis from eczema in RNA-later fixed skin samples. However, this type of skin sample is not regularly used in routine diagnostics. Therefore, we evaluated if the combination of NOS2 and CCL27 expression in lesional skin can be transferred to formalin-fixed paraffin embedded (FFPE) tissue. We present a FFPE-based molecular classifier (MC) that determines the probability for psoriasis with a specificity and sensitivity of 100% and 92%, respectively, and an area under the curve (AUC) of 0.97 delivering comparable results to the RNA-later based MC. The probability for psoriasis as well as the PCR result of NOS2 expression correlated positive with disease hallmarks of psoriasis and negative with eczema hallmarks. This tool now offers broad usage in pathology laboratories and can support diagnostic decision making on a molecular level.