Hashmi Atif Ali, Ali Rabia, Hussain Zubaida Fida, Faridi Naveen, Khan Erum Yousuf, Bakar Syed Muhammad Abu, Edhi Muhammad Muzzammil, Khan Mehmood
Histopathology department, Liaquat National Hospital and Medical College, Karachi, Pakistan.
Surgery department, Rhode Island Hospital and Brown University, Providence, Rhode Island, USA.
World J Surg Oncol. 2017 Jun 26;15(1):116. doi: 10.1186/s12957-017-1158-8.
Microsatellite instability (MSI) operates as the second major pathway in the colorectal carcinogenesis. Although genetic testing remains the gold standard for the detection of MSI, the College of American Pathologists (CAP) recommends an initial immunohistochemical workup with a four-antibody panel (MLH1, PMS2, MSH2, and MSH6) to screen for a defective mismatch repair system. An increased trend towards young age colorectal carcinoma (CRC) has been noticed in our population over recent years; however, neither screening for MSI by immunohistochemistry (IHC)/genetic testing was done nor were its morphological features studied. We aimed to determine the frequency of mismatch repair deficiency (dMMR) by loss of IHC expression of the aforementioned enzymes in CRC patients and its correlatation with clinicopathologic parameters.
This was a retrospective study conducted at Liaquat National Hospital, Karachi, between 2012 and 2015. A total of 100 cases of CRC were included in the study that underwent surgical resection. IHC stains using antibodies MLH1, PMS2, MSH2, and MSH6 were performed by DAKO EnVision method on representative tissue blocks. The results were interpreted by senior histopathologists and correlated with clinico-pathological parameters.
A total of 100 cases of CRC were studied that included 51 males and 49 females. Thirty-four percent (n = 34) of the patients showed loss of IHC staining for MMR markers. Combined loss of expression for MLH1/PMS2 were observed in 16% (n = 16) of the cases. Loss of MSH2/MSH6 were seen in 6% (n = 6) of the cases. Loss of expression for all markers were noted in 7% (n = 7) of the cases. There were 5% (n = 5) of the cases that showed isolated loss of MLH1 only. The tumors with dMMR status were significantly associated with right-sided location (p = 0.013), exhibited intra-tumoral lymphocytosis (p = 0.007), and lymphovascular invasion (p = 0.043). No significant association was seen with gender, age, tumor stage, grade, or other morphological features.
The frequency of mismatch repair deficiency in CRC patients was found to be 34% in Pakistani population which warrants further genetic testing to exclude Lynch syndrome. Moreover, right-sided location and intra-tumoral lymphocyte count may be used to identify patients who may need further workup.
微卫星不稳定性（MSI）是结直肠癌发生的第二条主要途径。尽管基因检测仍是检测MSI的金标准，但美国病理学家学会（CAP）建议首先使用四抗体组合（MLH1、PMS2、MSH2和MSH6）进行免疫组织化学检查，以筛查错配修复系统缺陷。近年来，我们人群中年轻结直肠癌（CRC）的发病率呈上升趋势；然而，既未通过免疫组织化学（IHC）/基因检测筛查MSI，也未研究其形态学特征。我们旨在通过上述酶的IHC表达缺失来确定CRC患者错配修复缺陷（dMMR）的频率及其与临床病理参数的相关性。
这是一项于2012年至2015年在卡拉奇利亚卡特国家医院进行的回顾性研究。该研究共纳入100例接受手术切除的CRC病例。使用DAKO EnVision方法对代表性组织块进行MLH1、PMS2、MSH2和MSH6抗体的IHC染色。结果由资深组织病理学家解读，并与临床病理参数相关联。
共研究了100例CRC病例，其中男性51例，女性49例。34%（n = 34）的患者显示MMR标志物的IHC染色缺失。16%（n = 16）的病例观察到MLH1/PMS2的联合表达缺失。6%（n = 6）的病例出现MSH2/MSH6缺失。7%（n = 7）的病例所有标志物表达均缺失。5%（n = 5）的病例仅显示MLH1单独缺失。dMMR状态的肿瘤与右侧位置显著相关（p = 0.013），表现为肿瘤内淋巴细胞浸润（p = 0.007）和淋巴管侵犯（p = 0.043）。与性别、年龄、肿瘤分期、分级或其他形态学特征未发现显著关联。
在巴基斯坦人群中，CRC患者错配修复缺陷的频率为34%，这需要进一步进行基因检测以排除林奇综合征。此外，右侧位置和肿瘤内淋巴细胞计数可用于识别可能需要进一步检查的患者。
