引言微卫星不稳定性(MSI)是结直肠癌(CRC)发病机制中的重要通路。MSI的发生是由于包括MutL蛋白同源物1(MLH1)在内的错配修复(MMR)基因突变,减数分裂后隔离增加2(PMS2),MutS同源物2(MSH2),和MutS同源物6(MSH6)。具有MSI的CRC被称为MMR缺陷(dMMR)CRC。相反,具有完整MMR基因的CRC称为微卫星稳定(MSS)或MMR熟练(pMMR)。在这项研究中,我们比较了dMMRCRC和pMMRCRC的临床病理特征。方法在组织病理学科进行回顾性研究,Liaquat国立医院,卡拉奇,巴基斯坦,从2020年3月到2022年2月,为期两年。该研究包括经活检证实的CRC并进行前期手术切除的病例。进行显微镜检查以评估肿瘤类型,grade,和入侵的程度,坏死的存在,神经周浸润(PNI),淋巴管浸润(LVI),肿瘤周围淋巴细胞(PTL),肿瘤内淋巴细胞(ITL),淋巴结转移。使用抗体进行免疫组织化学染色,即,MLH1、PMS2、MSH2和MSH6。肿瘤细胞中核表达的任何损失被称为dMMR或微卫星不稳定,而肿瘤细胞中完整的核表达被标记为MSS或pMMR。结果共纳入135例CRC患者。诊断时的平均年龄为46.76±17.74岁,女性占主导地位(60.7%)。MLH1,PMS2,MSH2和MSH6表达的损失占39.3%,34.1%,17.8%,和16.3%的病例,分别。总的来说,59.3%的CRC是pMMR,而dMMR占40.7%。注意到MMR状态与年龄之间的显着关联,PNI,LVI,肿瘤分级,肿瘤(T)和淋巴结(N)分期,粘液分化,ITL。dMMRCRC显著高于pMMRCRC50年。dMMRCRC中PNI和LVI的频率低于pMMRCRC。相反,较高等级(3级)和较高T期(T4)与dMMRCRC相关.或者,较高N级(N2b)的频率在pMMRCRC中更常见。此外,粘液性分化和ITL与dMMRCRC显著相关。结论我们人群中有相当比例的CRC患者表现出dMMR状态。dMMRCRC的组织学分级较高,粘液性分化频率较高,T分期较高。相反,LVI的存在,PNI,较高的N期与pMMRCRC相关。
Introduction Microsatellite instability (MSI) is an important pathway in colorectal carcinoma (CRC) pathogenesis. MSI occurs due to mutations in mismatch repair (MMR) genes that include MutL protein homolog 1 (MLH1), postmeiotic segregation increased 2 (
PMS2), MutS homolog 2 (MSH2), and MutS homolog 6 (MSH6). CRC with MSI is termed MMR deficient (dMMR) CRC. Conversely, CRC with intact MMR genes is called microsatellite stable (MSS) or MMR proficient (pMMR). In this study, we compared the clinicopathological features of dMMR CRC with pMMR CRC. Methods It was a retrospective study conducted in the Department of Histopathology, Liaquat National Hospital, Karachi, Pakistan, from March 2020 to February 2022, over a duration of two years. Biopsy-proven cases of CRC with upfront surgical resection were included in the study. Microscopic examination was performed to evaluate tumor type, grade, and extent of invasion, presence of necrosis, perineural invasion (PNI), lymphovascular invasion (LVI), peritumoral lymphocytes (PTL), intratumoral lymphocytes (ITL), and nodal metastasis. Immunohistochemical staining was performed using antibodies, namely, MLH1,
PMS2, MSH2, and MSH6. Any loss of nuclear expression in tumor cells was termed dMMR or microsatellite instable, whereas the intact nuclear expression in tumor cells was labeled as MSS or pMMR. Results A total of 135 cases of CRC were included in the study. The mean age at diagnosis was 46.76 ± 17.74 years, with female predominance (60.7%). The loss of MLH1,
PMS2, MSH2, and MSH6 expression was noted in 39.3%, 34.1%, 17.8%, and 16.3% cases, respectively. Overall, 59.3% of CRCs were pMMR, while 40.7% were dMMR. A significant association of MMR status was noted with respect to age, PNI, LVI, tumor grade, tumor (T) and nodal (N) stage, mucinous differentiation, and ITL. dMMR CRC was significantly above 50 years than pMMR CRC. The frequency of PNI and LVI was lower in dMMR CRC than in pMMR CRC. Conversely, the higher grade (grade 3) and higher T-stage (T4) were associated with dMMR CRC. Alternatively, the frequency of higher N stage (N2b) was more commonly seen in pMMR CRC. Moreover, mucinous differentiation and ITL were significantly associated with dMMR CRC. Conclusion A significant proportion of CRC patients in our population demonstrated dMMR status. dMMR CRC had a higher histological grade with a higher frequency of mucinous differentiation and higher T-stage. Conversely, the presence of LVI, PNI, and higher N stages were associated with pMMR CRC.