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

Highly 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. ### Competing Interest Statement The authors have declared no competing interest. ### Funding Statement This work was supported by the Medical Valley Award. ### Author Declarations I confirm all relevant ethical guidelines have been followed, and any necessary IRB and/or ethics committee approvals have been obtained. Yes The details of the IRB/oversight body that provided approval or exemption for the research described are given below: Ethical approval was granted by the ethical committee of the Klinikum rechts der Isar, Technical University Munich (project number 2773/10 and 515/17) I confirm that all necessary patient/participant consent has been obtained and the appropriate institutional forms have been archived, and that any patient/participant/sample identifiers included were not known to anyone (e.g., hospital staff, patients or participants themselves) outside the research group so cannot be used to identify individuals. Yes I understand that all clinical trials and any other prospective interventional studies must be registered with an ICMJE-approved registry, such as ClinicalTrials.gov. I confirm that any such study reported in the manuscript has been registered and the trial registration ID is provided (note: if posting a prospective study registered retrospectively, please provide a statement in the trial ID field explaining why the study was not registered in advance). Yes I have followed all appropriate research reporting guidelines and uploaded the relevant EQUATOR Network research reporting checklist(s) and other pertinent material as supplementary files, if applicable. Yes Generated data and codes can be provided upon request