# Immunohistochemical expression of smoothened in periocular basal cell, squamous cell and sebaceous carcinomas

## TL;DR

This study examines SMO protein levels in periocular skin cancers and finds that higher SMO expression correlates with increased tumor cell proliferation.

## Contribution

The study is the first to compare SMO expression and its correlation with proliferation in periocular BCC, SCC, and SEB.

## Key findings

- SMO expression was significantly higher in all tumor types compared to surrounding stroma.
- Higher SMO levels consistently correlated with higher Ki67 index across all three carcinomas.
- Hedgehog inhibitors may be clinically relevant for periocular SCC and SEB based on these findings.

## Abstract

Inhibition of Smoothened (SMO), a key protein in the Hedgehog signaling pathway, is effective for locally advanced basal cell carcinoma (BCC), but is not yet used for sebaceous carcinoma (SEB) or squamous cell carcinoma (SCC). This study quantified SMO expression and its relationship to proliferative activity in non-nodular periocular BCC, SEB and SCC. Tumor samples from 47 patients (17 BCC, 15 SCC, and 15 SEB) were immunostained and analyzed digitally to assess SMO optical density and Ki67 hot-spot index. SMO expression was significantly higher in all tumor types than in surrounding stroma, with no inter-tumor differences. SMO correlated with mitotic count in BCC but not in SCC or SEB, whereas higher SMO consistently paralleled a higher Ki67 index across all three carcinomas. These findings indicate that SMO expression and proliferative activity are closely linked and suggest that Hedgehog inhibitors, proven in BCC, warrant clinical evaluation as adjuvant or neoadjuvant therapy for periocular SEB and SCC.

The online version contains supplementary material available at 10.1038/s41598-025-06011-y.