The utility of the expression lack of DNA mismatch-repair (MMR) proteins in the detection of Lynch syndrome in endometrial hyperplasia as precursor lesion of endometrial carcinoma has not been well-established. The study investigated the immunoexpression pattern of MMR proteins in endometrial hyperplasia from Tunisian patients. We carried out a retrospective study of 60 endometrial hyperplasias diagnosed among Tunisian patients. Expression of MLH1, MSH2, MSH6, and PMS2 proteins was performed by immunohistochemistry on whole-slide sections of archival tissues. Analysis of MLH1 promoter methylation and microsatellite alterations was conducted in appropriate cases. Microsatellite instability screening was assessed using the Bethesda panel, including BAT25, BAT26, D17S250, D2S123, and D5S346 markers. Expression of MMR proteins was observed in all hyperplasias without atypia as well as in 27 out of 29 atypical hyperplasias. Only two atypical hyperplasias exhibited expression loss of MMR proteins. A single case revealed MSH6 expression lack. Expression loss of MLH1 and PMS2 was identified in another atypical hyperplasia and was associated with hypermethylation of MLH1 promoter. This patient had no familial history of endometrial cancer at the diagnostic time. The two deficient MMR cases showed microsatellite stable pattern. In conclusion, only two endometrial hyperplasias displayed an altered pattern of MMR expression. Our results suggest the limited utility of the immunohistochemical analysis of MMR protein in the early detection of Lynch syndrome in Tunisian patients diagnosed with endometrial hyperplasias. Multicenter studies with larger sample size are needed to more explore these findings.

中文翻译：

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DNA错配修复蛋白在子宫内膜增生中的免疫组织化学分析实用程序。

由于子宫内膜癌的前体病变，在子宫内膜增生中检测Lynch综合征时缺乏表达DNA错配修复（MMR）蛋白的表达的效用尚未得到很好的确立。该研究调查了突尼斯患者子宫内膜增生中MMR蛋白的免疫表达模式。我们对突尼斯患者中诊断出的60例子宫内膜增生进行了回顾性研究。MLH1，MSH2，MSH6和PMS2蛋白的表达是通过免疫组织化学在档案组织的整个切片上进行的。在适当的情况下进行了MLH1启动子甲基化和微卫星改变的分析。使用Bethesda面板评估了微卫星不稳定性筛选，包括BAT25，BAT26，D17S250，D2S123和D5S346标记。在所有无异型增生以及29个非典型增生中的27个中均观察到MMR蛋白的表达。仅两个非典型增生表现出MMR蛋白的表达损失。单个病例显示MSH6表达缺乏。MLH1和PMS2的表达缺失是在另一例非典型增生中发现的，并且与MLH1启动子的高甲基化有关。该患者在诊断时没有家族性子宫内膜癌病史。2例MMR缺陷病例均表现出微卫星稳定模式。总之，只有两个子宫内膜增生显示出MMR表达模式的改变。我们的结果表明，在诊断为子宫内膜增生的突尼斯患者中，MMR蛋白的免疫组织化学分析在早期检测Lynch综合征方面的作用有限。