<scp>MMP11</scp> as a Prognostic Indicator for Inverted Papilloma Histologic Grade and Recurrence

ABSTRACT Objectives Inverted papilloma (IP) is a benign, but locally aggressive sinonasal tumor with a high recurrence rate and potential for malignant transformation into squamous cell carcinoma ex‐IP (SCC). Currently, no reliable biomarkers exist to predict recurrence or severity. Matrix metalloproteinase‐11 (MMP11) has been implicated in tumor progression and extracellular matrix remodeling in various malignancies and has been shown to be progressively upregulated in IP transformation. This study investigates the relationship between MMP11 expression and IP histologic severity and recurrence risk. Methods Patient demographics and tumor characteristics were collected retrospectively at a tertiary care center from 2008 to 2023. Patient specimens were categorized into normal sinus tissue (NST), IP without dysplasia (IPND), IP with severe dysplasia (IPSD), and SCC. Immunohistochemical staining for MMP11 was performed, and quantitative analysis was conducted using DAB‐Quant software. Results A total of 52 patients were included, with a mean follow‐up of 68.8 months. MMP11 expression was significantly elevated in IPSD and SCC compared to IPND (36.7% and 36.5% vs. 21.1%, p = 0.02 and p = 0.01). Patients with recurrence exhibited higher MMP11 expression in their initial resection specimens compared to non‐recurrent cases (31.1% vs. 18.1%, p &lt; 0.01). High MMP11 expression (&gt; 50%) was associated with a shorter time to recurrence (17.5 vs. 32 months, p = 0.03), independent of histologic grade. Conclusion MMP11 expression correlates with increased IP histologic grade, risk of recurrence, and shorter time to recurrence. Elevated MMP11 expression may identify patients at higher risk for recurrence, allowing for targeted surveillance strategies and treatment options. Level of Evidence 3.