Epidermal growth factor receptor (EGFR) expression in periocular and extraocular sebaceous carcinoma.

Sebaceous carcinoma has a predominant periocular origin but can also be extraocular. These two groups have distinct clinical courses. Insight into the molecular determinants of tumorigenesis and metastasis is limited. There is no effective treatment for metastatic sebaceous carcinoma. Epidermal growth factor receptor (EGFR) is implicated in tumorigenesis and can be a therapeutic target in certain settings. We evaluated EGFR levels by immunohistochemistry (IHC), comparing its expression between periocular and extraocular tumors and assessed EGFR mutation status. IHC was performed in 36 cases: 19 periocular and 17 extraocular (10 associated with Muir-Torre syndrome-MTS). EGFR IHC was scored for percentage of positive cells (< 5%, 5-25%, 26-50%, > 50%) and intensity (+1 = low , +2 = moderate , +3 = high ). Extraocular carcinomas showed markedly increased levels of EGFR when compared to periocular carcinoma cases, both in terms of distribution (88% were > 25% of tumor cells vs. 16%) and intensity (77% were 2+ or 3+ vs. 21%) (p < 0.001). Among extraocular cases, there was significantly lower EGFR expression in MTS-related cases (p < 0.05). No EGFR mutations were identified. Our results underscore the divergent mechanisms underlying the tumorigenesis of periocular and extraocular sebaceous carcinoma and suggest an association between aggressive behavior and increased EGFR expression in extraocular sebaceous carcinoma.