Loss of mismatch repair proteins in sebaceous gland tumors

Background: Sebaceous gland neoplasms are rare tumors that are associated with visceral malignancies in patients with Muir–Torre syndrome (MTS). The majority of the MTS‐associated tumors reveal mutations in DNA mismatch repair (MMR) genes (most often hMSH‐2 and hMLH‐1) and microsatellite instability. The sebaceous gland lesions in patients with MTS can often precede or occur concurrently with the visceral neoplasms. The early recognition of those lesions and their differentiation from sporadic sebaceous gland tumors are critical for proper patient management. Here we investigate the MMR gene expression in a variety of sebaceous gland tumors, with or without associated visceral malignancy. Methods: We studied the expressions of hMLH‐1 and hMSH‐2 in 10 consecutive sebaceous hyperplasias, 10 sebaceus nevi, 12 sebaceous adenomas, seven sebaceous carcinomas and the adjacent normal sebaceous glands using immunohistochemistry and paraffin‐embedded sections. Results: The normal sebaceous glands and the glands of all the sebaceus nevi were positive for hMLH‐1 and hMSH‐2. Loss of hMSH‐2 expression was found in 1/10 (10%) sebaceous hyperplasias, 3/12 (25.0%) sebaceous adenomas, and 2/7 (28.6%) sebaceous carcinomas. Loss of hMLH‐1 expression was seen in 1/10 (10%) hyperplasias, 3/12 (25.0%) adenomas, and 1/7 (14.3%) carcinomas. No concurrent loss of both hMLH‐1 and hMSH‐2 was observed. Loss of MMR (either hMLH‐1 or hMSH‐2) was detected in 80% of the benign sebaceous lesions associated with malignancy. In comparison, only 23% of sebaceous lesions not associated with malignancy showed loss of MMR proteins. No loss of hMSH‐2 protein was found in the visceral cancer in one patient with hMSH‐2‐negative sebaceous adenoma. Conclusions: Our results confirm the previous reports of alterations of mismatch repair genes in the sebaceous neoplasms of patients with MTS. However, we showed that those changes also occur early at the stage of sebaceous hyperplasia, even in the absence of a visceral malignancy. This indicates the importance of the abnormal DNA mismatch repair in the progression of this disease.