FFPE-Based Molecular Classifier Precisely Separates Eczema From Psoriasis

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The first evening of the 2023 Revolutionizing Atopic Dermatitis conference began with a poster reception, unveiling numerous new abstracts for viewing and discussion. From the group of accepted posters came, “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,” from Fischer et al.¹

The study investigators sought to develop a real-time based molecular classifier (MC) to distinguish psoriasis from atopic eczema in FFPE-fixed skin samples for diagnostic measures and to evaluate the potential of minimally invasive microbiopsies and non-invasive tape strips for molecular diagnosis. Developing an MC capable of distinguishing psoriasis from atopic eczema was important to the investigators, as they noted that highly specific and efficient drugs have been recently developed to treat non-communicable chronic inflammatory skin diseases (ncISD). Due to these drugs’ specificity, they require precise diagnostics to attribute the most efficient treatment for each patient.

Additionally, diagnosis is complicated by the complex pathogenesis of ncISDs and their clinical and histological overlap. Precise diagnosis of psoriasis and eczema is difficult in special cases and molecular tools need to be developed to support gold standard diagnosis, according to the investigators. A gene expression-based classifier using NOS2 and CCL27 has been proposed and its clinical validity has been examined and proven in various patient cohorts.

In their study, investigators collected FFPE, micro-( Ø1mm) and macrobiopsies (Ø4-6mm), and tape strips from psoriasis and eczema lesions which were analyzed by real-time PCR for the expression of NOS2 and CCL27. A molecular classifier (MC) was established using a linear regression model.

The investigators reported that “The FFPE-based classifier determined probabilities for psoriasis with a sensitivity and specificity, and of 92% and 100%, respectively, and an AUC of 0.97. To test if microbiopsies are also adequate tissue samples for the MC, we analyzed gene expression in 83 pairs of macro-and microbiopsies by qRT-PCR. Delta-CT values showed no significant difference between macro-and microbiopsies. Delta Ct values of NOS2 and CCL27 also efficiently separated psoriasis from eczema samples in inflamed skin collected via tape strips.”

From their findings, the investigators concluded that FFPE-based MC precisely separates eczema from psoriasis and efficiently identifies subtypes of both diseases, demonstrating a possible implementation of this molecular diagnostic aid in routine clinical pathological practice. Additionally, they noted that gene expression profile of RNA later fixed microbiopsies is comparable to standard 4-6mm biopsies and that microbiopsies are equally suited for the MC.

Reference

1. Fischer F, Doll A, Uereyener D, et al. 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. Poster presented at: 2023 Revolutionizing Atopic Dermatitis Conference; April 29-May 1, 2023; Washington, DC.