错配修复缺陷的胃癌微卫星不稳定性及临床病理特征分析

Analysis of Microsatellite Instability and Clinical Pathological Features in Gastric Cancer with Mismatch Repair Deficiency

摘要: 目的：研究免疫组织化学(Immunohistochemistry, IHC)结果为错配修复缺陷(Mismatch Repair deficiency, dMMR)的胃癌中微卫星不稳定状态(Microsatellite Instability, MSI)，比较胃癌中dMMR/MSI不同检测方法一致性，分析dMMR胃癌临床病理特征。方法：选取2020年3月至2022年7月青岛大学附属医院术前未经治疗、接受胃癌根治术的错配修复(Mismatch Repair, MMR)蛋白IHC检测结果为dMMR的病例85例，由2名病理医师对IHC结果进行复核。利用聚合酶链式反应(Polymerase Chain Reaction, PCR)对85例同样本进行MSI状态的检测，同时分析dMMR胃癌临床病理特征。结果：在85例胃癌样本中，经复核，IHC结果均为dMMR，其中3例经PCR法测定为微卫星稳定(Microsatellite Stability, MSS)，免疫组化检测dMMR与PCR检测结果的一致率为96.47%。本研究中dMMR胃癌患者以男性多见(61.2%)，初诊时中位年龄在70岁(45岁~86岁)，好发于胃窦(76.5%)，以MLH1与PMS2这两种MMR蛋白联合缺失为主(94%)，Lauren分型中混合型较多(43.5%)，分期以II期为主(54.1%)，PD-L1表达CPS ≥ 5 (81.2%)，EBER表达为阴性(98.9%)，HER2基因均无扩增(100%)，所有患者中大部分未接受辅助化疗(68.2%)，截至随访时间，有85.9%患者未出现复发以及转移(中位随访时间17月)。结论：本研究强调了免疫组化和聚合酶链式反应在检测胃癌错配修复缺陷和微卫星不稳定性方面的显著相关性。主要临床病理特征包括以老年男性为主，好发于胃窦，分期较早，预后较好。

Abstract: Objective: This study is dedicated to assessing mismatch repair deficiency (dMMR) in gastric cancer utilizing immunohistochemistry (IHC) and determining microsatellite instability (MSI) via polymerase chain reaction (PCR) testing. Its primary aim is to evaluate the consistency between these diagnostic methods for dMMR and MSI in gastric cancer, and to comprehensively analyze the clinical-pathological features that characterize these molecular markers. Methods: Between March 2020 and July 2022, we selected 85 gastric cancer patients from The Affiliated Hospital of Qingdao University who had not received prior treatment and underwent radical surgery. These cases exhibited dMMR based on immunohistochemistry (IHC) results for mismatch repair proteins. The IHC results were reviewed by two pathologists. Polymerase chain reaction (PCR) was employed to evaluate MSI status in the same cohort. Concurrently, we analyzed the clinicopathological characteristics of dMMR/MSI-H gastric cancer. Results: In the analysis, all 85 gastric cancer samples exhibited mismatch repair deficiency (dMMR), as determined by immunohistochemistry (IHC). Polymerase chain reaction (PCR) testing on these samples identified 3 cases as microsatellite stable (MSS). The concordance rate between IHC for dMMR and PCR results in these gastric cancer samples was 96.47%. The cohort predominantly consisted of male patients (61.2%), presenting a median age of 70 years at initial diagnosis (range: 45~86 years). The tumors were primarily located in the gastric antrum (76.5%) and displayed a joint loss of MLH1 and PMS2 MMR proteins in 94% of cases. Regarding histology, the mixed subtype according to the Lauren classification was most frequent (43.5%). Stage II tumors were the most common (54.1%). PD-L1 expression, with a combined positive score (CPS) of ≥5, was observed in 81.2% of the cases. EBER expression was negative in 98.9% of cases, and no HER2 gene amplification was detected across the cohort (100%). A majority of patients (68.2%) did not undergo adjuvant chemotherapy. As of the last follow-up, with a median duration of 17 months, 85.9% of patients exhibited no signs of recurrence or metastasis. Conclusion: This study underscores a significant correlation between immunohistochemistry and polymerase chain reaction in detecting mismatch repair deficiency and microsatellite instability in gastric cancer. Key clinical-pathological features include a predominance of the condition in elderly males and a frequent tumor localization in the gastric antrum, leading to a generally favorable prognosis for these patients.