Loss of mismatch repair proteins in sebaceous gland tumors

Abstract

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-1and 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-1and 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 in1/10 (10%) hyperplasias, 3/12 (25.0%) adenomas, and1/7 (14.3%) carcinomas. No concurrent loss of both hMLH-1and hMSH-2 was observed. Loss of MMR (either hMLH-1or 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.

Mismatch Repair Proteins Expression and Microsatellite Instability in Skin Lesions With Sebaceous Differentiation: A Study in Different Clinical Subgroups With and Without Extracutaneous Cancer

“…For sporadic sebaceous lesions, these data are within the range reported by the literature, which varies from 0% 19 to 23%. 18,20 In contrast, the percentage of MMR 2 sebaceous lesions associated with visceral tumors was significantly lower than previously reported. 19,20 This discrepancy could be related to differences in the way that cases were recruited.…”

“…18,20 In contrast, the percentage of MMR 2 sebaceous lesions associated with visceral tumors was significantly lower than previously reported. 19,20 This discrepancy could be related to differences in the way that cases were recruited. In particular, in this study, patients were not selected according to age or family history.…”

Discordant Architectural and Cytological Features in Cutaneous Sebaceous Neoplasms-A Classification Dilemma: Report of 5 Cases

“…Although the possibility that this patient has MTS cannot be totally refuted (some patients with MTS develop extracutaneous tumors many years after the diagnosis of a cutaneous lesion), this case may be equally regarded as sporadic; loss of MMR protein has been reported in sporadic cutaneous sebaceous neoplasms. 15 Interestingly, this single MLH1-deficient tumor was situated on the chest wall. A recent study examining the association of sebaceous tumor type and site with MMR status showed that sebaceous neoplasms that occur outside of the neck and neck area are very likely to be MMR deficient.…”

A jéghegy csúcsa: multiplex faggyúmirigy-eredetű bőrtumor coloncarcinomában. Muir–Torre-szindróma

“…A módszer szenzitív, adott MMR-fehérjére specifi kus és könnyen reprodukálható. Hátránya, hogy a negatív eredmény nem zárja ki az MMR-génmutációt [28,29,30]. Másodvonalbeli tesztként az MSI-elemzés alkalmazható.…”