Javeed Saira, Chughtai Anila, Zafar Ghazi, Khalid Fatima, Batool Ayma, Chughtai Akhtar S
Histopathology, Chughtai Institute of Pathology, Lahore, PAK.
Cureus. 2022 Jul 29;14(7):e27448. doi: 10.7759/cureus.27448. eCollection 2022 Jul.
Background and objective Mismatch repair (MMR) proteins are an integral part of the cell cycle, and they play an important role in the genomic stability of the microsatellite complex. Microsatellite instability (MSI) is associated with Lynch and multi-tumor syndromes. Identifying patients with Lynch syndrome is essential for screening, early detection, and surveillance of other Lynch syndrome-associated tumors. The role of MMR deficiency is well known in colorectal and endometrial adenocarcinoma. However, the role of MMR deficiency in prostatic adenocarcinoma is a matter of controversy. A few studies have been published to analyze the association between MMR deficiency and prostatic adenocarcinoma. In this study, we used immunohistochemistry to look into the expression of four MMR proteins in prostatic adenocarcinoma: MSH2, MSH6, MLH1, and PMS2. Methodology This was a cross-sectional descriptive study involving 74 cases of acinar prostatic adenocarcinoma, diagnosed with hematoxylin & eosin (H&E), over a period of six months between December 2021 and May 2022 at the Chughtai Institute of Pathology in Lahore, Pakistan. We performed the immunohistochemical (IHC) analysis and interpretation of four antibodies, i.e., MSH2, MSH6, MLH1, and PMS2. Results In our study, the age of the patients ranged from 50 to 98 years, with a mean age of 67.99 ± 9.59 years. The specimens were collected through transurethral resection of the prostate (TURP), transurethral vaporization of the prostate (TVP), core biopsy, and radical prostatectomy. Isolated loss of each MSH2 and PMS2 was noted in nine cases (12.20%) and MSH6 in two cases (2.70%). There was no loss noted for MLH1. Furthermore, simultaneous loss of MSH2/MSH6 was observed in one case (1.35%). Conclusion Our study findings revealed a low frequency of IHC expression of MMR proteins, especially the concurrent loss of paired MMR proteins. However, prostatic adenocarcinoma is associated with the isolated loss of MMR proteins. Thus, the present study does not warrant reflex testing/screening in every case of prostatic adenocarcinoma, because of its low frequency, which is probably suggestive of its sporadic pattern.
背景与目的 错配修复（MMR）蛋白是细胞周期的一个组成部分，它们在微卫星复合体的基因组稳定性中发挥重要作用。微卫星不稳定性（MSI）与林奇综合征和多肿瘤综合征相关。识别林奇综合征患者对于筛查、早期检测和监测其他林奇综合征相关肿瘤至关重要。MMR缺陷在结直肠癌和子宫内膜腺癌中的作用已广为人知。然而，MMR缺陷在前列腺腺癌中的作用存在争议。已经发表了一些研究来分析MMR缺陷与前列腺腺癌之间的关联。在本研究中，我们使用免疫组织化学来研究四种MMR蛋白在前列腺腺癌中的表达：MSH2、MSH6、MLH1和PMS2。
方法 这是一项横断面描述性研究，涉及74例腺泡状前列腺腺癌病例，于2021年12月至2022年5月期间在巴基斯坦拉合尔的楚格泰病理研究所通过苏木精和伊红（H&E）诊断，为期六个月。我们对四种抗体，即MSH2、MSH6、MLH1和PMS2进行了免疫组织化学（IHC）分析和解读。
结果 在我们的研究中，患者年龄范围为50至98岁，平均年龄为67.99±9.59岁。标本通过经尿道前列腺切除术（TURP）、经尿道前列腺汽化术（TVP）、穿刺活检和根治性前列腺切除术采集。在9例（12.20%）中观察到MSH2和PMS2各自单独缺失，在2例（2.70%）中观察到MSH6缺失。未观察到MLH1缺失。此外，在1例（1.35%）中观察到MSH2/MSH6同时缺失。
结论 我们的研究结果显示MMR蛋白的免疫组织化学表达频率较低，尤其是配对MMR蛋白的同时缺失。然而，前列腺腺癌与MMR蛋白的单独缺失相关。因此，由于其低频率，本研究不支持对每例前列腺腺癌进行反射性检测/筛查，这可能提示其散发性模式。
