Molecular Signatures as a New Classification Scheme for CRS

Abstract

Objective: We have identified 2 distinct gene expression patterns (CRS1 and CRS2) in cultured epithelial cells obtained from surgical biopsies in CRS patients with and without nasal polyps (NP), which may better classify this disorder. We wished to compare the cellular infiltrate in CRS when assessed by molecular and clinical phenotypes. Method: Surgical biopsies taken from 20 CRS patients and 10 controls were divided according to their molecular signature as determined from epithelial cell cultures. Immunohistochemistry (IHC) for neutrophil elastase (NE) and major basic protein (MBP) was used to identify neutrophils and eosinophils in the epithelial and submucosal areas. Results: Groups were analyzed statistically using ANOVA and t test to identify significant differences between groups. When biopsies were assessed as function of the clinical phenotypes of CRSwNP compared with CRSsNP, while there were equal increases in the number of eosinophils and neutrophils cells in CRS patients compared with the control subjects, there was no difference between the win and sNP groups. However, when assessed according to molecular signature, while there was an increase in eosinophils in both groups, a significant increase in the number of neutrophils was only seen in the CRS2 group, suggesting a different pathogenic mechanism. Conclusion: This novel expression signature identifies a molecular phenotype of CRS that is characterized by a marked neutrophil infiltration. Assessments of disease mechanism and response to therapy according to molecular, as opposed to clinical, phenotype may identify mechanistic differences which “personalize” our management of individuals with this disease.