Expression of SIRT1 in Ocular Surface Squamous Neoplasia

BACKGROUND:The class III histone deacetylase SIRT1 is overexpressed in many malignancies and has been implicated in inactivating proteins that are involved in tumor suppression and DNA damage repair. In the current study, we examined the expression of SIRT1 in normal epithelium (NE) compared with ocular surface squamous neoplasia (OSSN) to elucidate a possible role for SIRT1 in the development or progression of this malignancy. METHODS:We examined SIRT1 expression by immunohistochemistry in 47 cases of OSSN and 10 specimens of NE. Our sample included 11 benign lesions (papillomas), 25 cases of conjunctival intraepithelial neoplasia, and 11 malignant lesions of squamous cell carcinoma. The extent of staining and intensity was scored and the combined raw data were then converted to the German Immunoreactive Score. RESULTS:Nuclear and cytoplasmic expression of SIRT1 was observed in all cases of OSSN. For the NE specimens, 50% showed negative expression and 30% weak expression, and 20% were considered significantly immunoreactive. The differential expression of SIRT1 between NE and OSSN was statistically significant (P < 0.0001). Additionally, when the staining pattern in cases of conjunctival intraepithelial neoplasia was evaluated, the staining of the more differentiated surface cells was remarkably weaker compared with the cells located closer to the basal membrane. CONCLUSIONS:SIRT1 may play an important role in the development and progression of epithelial tumors of the conjunctiva. Further research into the potential of SIRT1 as a novel therapeutic target is warranted.