Related Experiment Video
Updated: Jun 18, 2026
Cell Population Analyses During Skin Carcinogenesis
Published on: August 21, 2013
Immunohistochemical expression of smoothened in periocular basal cell, squamous cell and sebaceous carcinomas
Gustav Stålhammar1,2,3, Basel Haj Hasan4, Krzysztof W Kotowski5,6
1St. Erik Ophthalmic Pathology Laboratory, St. Erik Eye Hospital, Stockholm, Sweden. gustav.stalhammar@ki.se.
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.
Insights
Smoothened (SMO) protein is highly expressed in periocular basal cell carcinoma (BCC), sebaceous carcinoma (SEB), and squamous cell carcinoma (SCC). Higher SMO levels correlate with increased cell proliferation, suggesting SMO inhibitors could treat these skin cancers.
Area of Science:
- Oncology
- Dermatology
- Molecular Biology
Background:
- The Hedgehog signaling pathway, mediated by Smoothened (SMO), is a target for basal cell carcinoma (BCC) treatment.
- SMO's role in sebaceous carcinoma (SEB) and squamous cell carcinoma (SCC) remains less understood, particularly in periocular tumors.
Purpose of the Study:
- To quantify SMO expression in non-nodular periocular BCC, SEB, and SCC.
- To investigate the correlation between SMO expression and tumor proliferative activity (Ki67 index and mitotic count).
Main Methods:
- Immunohistochemical staining for SMO and Ki67 on 47 tumor samples (17 BCC, 15 SCC, 15 SEB).
- Digital image analysis to quantify SMO optical density and Ki67 hot-spot index.
- Correlation analysis with mitotic count.
Main Results:
- SMO expression was significantly elevated in all three tumor types compared to surrounding stroma.
- SMO expression levels did not differ significantly among BCC, SEB, and SCC.
- SMO correlated with mitotic count in BCC but not in SEB or SCC.
- Higher SMO expression consistently paralleled a higher Ki67 proliferation index across all tumor types.
Conclusions:
- SMO expression is closely linked to proliferative activity in periocular BCC, SEB, and SCC.
- Hedgehog pathway inhibitors, effective in BCC, may hold therapeutic potential for periocular SEB and SCC.
- Further clinical evaluation of SMO inhibitors as adjuvant or neoadjuvant therapy for SEB and SCC is warranted.
