DNA Mismatch Repair in Periocular Sebaceous Carcinoma.
KDA Rajan, Christopher Burris, Nicholas Iliff, Michael Grant, Jim Eshleman, Charles G Eberhart. Johns Hopkins University, Baltimore, MD; Maryland General Hospital, Baltimore; Johns Hopkins Hospital, Baltimore, MD
Background: Sebaceous carcinomas of the eyelid are rare but aggressive tumors. While sebaceous neoplasms can be associated with Muir-Torre syndrome, such systemic features are uncommon in patients with ocular adnexal sebaceous carcinoma. Patients with Muir-Torre syndrome most often demonstrate loss of one of several mismatch repair genes, leading to genomic instability in the form of microsatellite instability. However, the role of mismatch repair gene abnormalities in sporadic sebaceous carcinomas of the ocular adnexa remains poorly understood. The aim of our study was to assess mismatch repair in sporadic periocular tumors.
Design: Hematoxylin-and-eosin stained slides from eleven sebaceous carcinomas of the ocular adnexa were reviewed to verify the diagnosis as well as to note their extent. Ten of these were sporadic cases, and one was from a patient with known Muir-Torre syndrome. Immunohistochemistry was used to analyze the presence of four mismatch repair (MMR) proteins (MLH1, MSH2, MSH6, and PMS2) in these tumors. The tumors demonstrated either strong positive staining or total lack of staining for these MMR proteins, which was interpreted as either MMR intact or MMR deficient respectively. DNA was extracted from 7 of the larger tumors as well as adjacent normal control tissue, and subjected to microsatellite instability (MSI) analysis using 5 highly sensitive mononucleotides and 2 pentanucleotides.
Results: All ten of the presumed sporadic ocular adnexal sebaceous carcinomas maintained strong staining of all four of the mismatch repair genes tested. The Muir-Torre syndrome associated tumor showed loss of staining for the mismatch repair genes MSH2 and MSH6. MSI testing of seven tumors showed low microsatellite instability in the Muir-Torre associated tumor, and no microsatellite instability in the remaining cases.
Conclusions: Sporadic sebaceous carcinoma of the ocular adnexa are neither associated with a loss of mismatch repair genes, nor microsatellite instability. This distinguishes them from those associated with Muir-Torre Syndrome, and from sporadic tumors at other sites.
Wednesday, March 2, 2011 1:00 PM
Poster Session VI # 286, Wednesday Afternoon