Investigation of the Relationship Between Immunohistochemical Mismatch Repair (MMR) Protein Expression and Prognostic Parameters in Endometrial Carcinomas

G. Serin, P. Savaş, N. Özdemir, O. Zekioğlu, L. Akman
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Abstract

Objective: Molecular classification has been the most important development in endometrial carcinomas in recent years. This classification divides tumors into four groups: (i) POLE mutant group, (ii) microsatellite instable (MSI) group, (iii) high copy number group (P53 mutation), and (iv) low copy number group. Among these groups, POLE and MSI groups stand out with their better prognosis and potential to benefit from immune-control inhibitor therapy. In our study, we aimed to compare the prognostic parameters of patients with and without nuclear expression loss in MMR proteins (MLH-1, PMS-2, MSH-2, MSH-6) by immunohistochemical (IHC) method. Methods: Between 2017 and 2020, 80 patients who were diagnosed with endometrial carcinoma in hysterectomy material and whose MMR proteins were evaluated as IHC were included in the study. Patients with and without MMR loss were compared in terms of tumor size, histological grade (HD), depth of myometrial invasion, lymphovascular invasion (LVI), and cervical involvement. Results: Loss of any of the MMR proteins was present in 37 cases (46.3%), while 43 cases (53.7%) had no loss. When the cases were compared in terms of loss of MMR protein nuclear expression, 45.9% (17/37) of the cases with loss and 27.9% (12/43) of the cases without loss had histologic grade III (P = 0.03). There was no statistically significant difference between the two groups in terms of myometrium 1/2 external invasion, cervical stromal involvement, and LVI. Conclusion: Approximately half of the patients in our study lost at least one of the MMR proteins. The most common losses were MLH-1 and PMS-2. The HD of patients with loss of nuclear expression of MMR proteins tended to be statistically significantly higher than those without loss.
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子宫内膜癌免疫组化错配修复(MMR)蛋白表达与预后参数关系的研究
目的:分子分型是近年来子宫内膜癌研究的重要进展。这种分类将肿瘤分为四组:(i) POLE突变组,(ii)微卫星不稳定(MSI)组,(iii)高拷贝数组(P53突变),(iv)低拷贝数组。在这些组中,POLE和MSI组以其更好的预后和从免疫控制抑制剂治疗中获益的潜力而突出。在我们的研究中,我们旨在通过免疫组化(IHC)方法比较MMR蛋白(MLH-1, PMS-2, MSH-2, MSH-6)核表达缺失和非核表达缺失患者的预后参数。方法:2017年至2020年,80例子宫切除术材料中诊断为子宫内膜癌且MMR蛋白评估为IHC的患者纳入研究。在肿瘤大小、组织学分级(HD)、肌层浸润深度、淋巴血管浸润(LVI)和颈椎受累方面,比较了MMR丢失和非MMR丢失患者。结果:37例(46.3%)患者出现MMR蛋白缺失,43例(53.7%)患者未出现MMR蛋白缺失。比较MMR蛋白核表达缺失的病例时,45.9%(17/37)的丢失病例和27.9%(12/43)的未丢失病例的组织学级别为III级(P = 0.03)。两组在肌层1/2外侵、宫颈间质受累和LVI方面无统计学差异。结论:在我们的研究中,大约一半的患者至少丢失了一种MMR蛋白。最常见的损失是MLH-1和PMS-2。MMR蛋白核表达缺失患者的HD倾向于高于未缺失患者。
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