Expression of the Epidermal Growth Factor Receptor (EGFR) Ligand Heparin-Binding EGF-Like Growth Factor (HB-EGF) in Sinonasal Inverted Papilloma

Objectives Nasal sinonasal inverted papillomas (SIP) are benign tumors with malignant potential that may progress to squamous cell carcinoma (SCC). Epidermal growth factor receptor (EGFR) expression is central to the development and malignant transformation of SIP, but the expression of its ligand, heparin-binding EGF-like growth factor (HB-EGF), and the regulators of HB-EGF expression have not been fully investigated. This study aimed to examine the expression of HB-EGF and its regulatory factors in SIP. Methods The expression of HB-EGF, EGFR, and phosphorylated EGFR (p-EGFR) was immunohistochemically examined in 32 patients with SIP, 3 with SIP-associated sinonasal squamous cell carcinoma (IPSCC), and 27 with de novo SCC arising in the sinonasal cavity (dnSCC). We also evaluated the expression of HIF-1α, an activator of ADAM12, which promotes the shedding of cytoplasmic membrane-bound HB-EGF from the cell surface. Results Among the 32 patients with SIP, most corresponded to Krouse stages T2-T3 and originated mainly in the maxillary or ethmoid sinus. All three cases of IPSCC were of the keratinizing type and classified as T4a. The 27 dnSCC cases were predominantly keratinizing type, arising chiefly in the maxillary sinus, and staged as T3-T4. HB-EGF and ADAM12 were expressed in all SIP and IPSCC cases, whereas the HB-EGF positivity rate was significantly lower in dnSCC (p < 0.05). EGFR and ADAM12 were broadly expressed across groups without significant differences, while p-EGFR expression was significantly higher in SIP and IPSCC compared with dnSCC (p < 0.05). Correlation analysis demonstrated a strong association between ADAM12 and HIF-1α, with weaker positive correlations observed between ADAM12 and HB-EGF, and between HB-EGF and p-EGFR. Conclusion HB-EGF expression is a characteristic feature of SIP. ADAM12 and HIF-1α may contribute to the distinctive upregulation of HB-EGF observed in SIP.