Relation of epidermal growth factor receptor expression to goblet cell hyperplasia in nasal polyps

• Published in: Journal of allergy and clinical immunology Vol. 106; no. 4; pp. 705 - 712
• Main Authors: Burgel, Pierre-Regis, Escudier, Estelle, Coste, Andre, Dao-Pick, Trang, Ueki, Iris F., Takeyama, Kiyoshi, Shim, Jae Jeong, Murr, Andrew H., Nadel, Jay A.
• Format: Journal Article
• Language: English
• Published: New York, NY Mosby, Inc 01.10.2000; Elsevier
• Subjects: Airway epithelium; Biological and medical sciences; Cell Movement; eosinophils; epidermal growth factor receptor; Epithelial Cells - metabolism; Gene Expression; Goblet Cells - pathology; Humans; Hyperplasia - metabolism; Medical sciences; mucin MUC5AC; Mucins - genetics; nasal polyps; Nasal Polyps - metabolism; Nasal Polyps - pathology; neutrophils; Neutrophils - cytology; Otorhinolaryngology. Stomatology; Receptor, Epidermal Growth Factor - biosynthesis; Receptor, Epidermal Growth Factor - genetics; Tumor Necrosis Factor-alpha - analysis; Tumor Necrosis Factor-alpha - immunology; Tumors; Upper respiratory tract, upper alimentary tract, paranasal sinuses, salivary glands: diseases, semeiology; mucin MUC5AC; TGF; epidermal growth factor receptor; AB/PAS; nasal polyps; eosinophils; Airway epithelium; neutrophils; EGFR; HNE; Human; Pathophysiology; Upper respiratory tract; Hyperplasia; Cytokine; Mucus; Goblet cell; Growth factor receptor; Epidermal growth factor; Polypeptide; Nose; Growth factor; Polyp; Biological receptor
• ISSN: 0091-6749
• DOI: 10.1067/mai.2000.109823

Background: Because the epidermal growth factor receptor (EGFR) system regulates mucin production in airway epithelium, we hypothesized a role for this system in mucus hypersecretion that occurs in nasal polyposis. Objective: We examined the relationship between goblet cell hyperplasia, EGFR expression, and inflammatory mediators produced by eosinophils and neutrophils in nasal polyp tissues. Methods: Nasal polyp tissue samples from 8 patients and nasal turbinate biopsy specimens from 6 normal control subjects were examined for alcian blue/PAS staining, mucin MUC5AC (MUC5AC), and EGFR immunoreactivity and EGFR gene expression (in situ hybridization). We also examined the role of eosinophils and neutrophils in goblet cell hyperplasia. Results: In control nasal mucosa alcian blue/periodic acid–Schiff– and MUC5AC-stained areas were 18.40% ± 1.31% and 21.89% ± 1.43%, respectively. In polyps the alcian blue/periodic acid–Schiff– and MUC5AC-stained areas were 51.30% ± 5.85% and 52.07% ± 6.58%, which was significantly larger than that found in control subjects (each comparison, P < .01). Four of 6 control specimens expressed EGFR messenger RNA and protein weakly in the epithelium. In polyps 4 of 8 specimens expressed EGFR gene and EGFR protein strongly; the EGFR-stained area was greater in hyperplastic than in pseudostratified epithelium. TNF-α immunoreactivity, expressed in eosinophils, was increased in EGFR-positive polyps compared with EGFR-negative polyps, suggesting a role for TNF-α in EGFR expression. Neutrophils were increased in the epithelium of EGFR-positive compared with EGFR-negative polyps, suggesting a role for these cells in mucin expression and in goblet cell degranulation. Conclusion: These data suggest a role for EGFR cascade in the regulation of goblet cell mucins in nasal polyps. Proof of concept will require clinical studies using selective EGFR inhibitors. (J Allergy Clin Immunol 2000;106:705-12.)