[1]郝美玲,张秀芬,李子鑫,等.胃癌组织中MLH1，MSH2，MSH6 和PMS2 表达及与临床病理特征和预后的相关性分析[J].现代检验医学杂志,2023,38(02):48-51+62.[doi:10.3969/j.issn.1671-7414.2023.02.009 ]
　HAO Mei-ling,ZHANG Xiu-fen,LI Zi-xin,et al.Correlation between the Expression of MLH1, MSH2, MSH6, PMS2 and Clinicopathological Features and Prognosis in Gastric Cancer[J].Journal of Modern Laboratory Medicine,2023,38(02):48-51+62.[doi:10.3969/j.issn.1671-7414.2023.02.009 ]
点击复制

胃癌组织中MLH1，MSH2，MSH6 和PMS2 表达及与临床病理特征和预后的相关性分析()
分享到：

《现代检验医学杂志》[ISSN:/CN:]

卷:
第38卷
期数:
2023年02期
页码:
48-51+62
栏目:
论著
出版日期:
2023-03-15

文章信息/Info

Title:
Correlation between the Expression of MLH1, MSH2, MSH6, PMS2 and Clinicopathological Features and Prognosis in Gastric Cancer
文章编号:
1671-7414（2023）02-048-05
作者:
郝美玲; 张秀芬; 李子鑫; 李姗姗; 李春辉
（承德医学院附属医院病理科，河北承德 067000）
Author(s):
HAO Mei-ling;  ZHANG Xiu-fen;  LI Zi-xin;  LI Shan-shan;  LI Chun-hui
（Department of Pathology, Affiliated Hospital of Chengde Medical College, Hebei Chengde 067000，China）
关键词:
MLH1蛋白; MSH2蛋白; MSH6蛋白; PMS2蛋白; 胃癌
分类号:
735.2；R730.43
DOI:
10.3969/j.issn.1671-7414.2023.02.009
文献标志码:
A
摘要:
目的 探讨胃癌组织中错配修复蛋白 MutL homologue 1（MLH1），MutS homologue 2（MSH2），MutS homologue 6（MSH6）和减数分裂后分离为 2（postmeiotic segregation increased 2 ，PMS2）的表达及与临床病理特征和预后的相关关系。方法 选取承德医学院附属医院病理科 2018年 11月～2021年 11月确诊的 474例胃癌组织为研究对象，采用免疫组织化学 SP法检测胃癌组织中 MLH1，MSH2，MSH6和 PMS2蛋白表达水平，根据此四种蛋白表达情况将胃癌组织分为高频微卫星不稳定（microsatellite instability-high, MSI-H）组和低频微卫星不稳定或微卫星稳定 (microsatellite instability - low/ microsatellite stability, MSI-L/MSS)组，比较两组的临床病理特点。采用 Kaplan-Meier 生存分析法比较两组患者的预后情况。结果 474例胃癌中，MSI-L/MSS型胃癌为 403例（85.02%），MSI-H型胃癌共 71例（14.98%）。其中 4种错配修复蛋白 MLH1，MSH2，MSH6和 PMS2任一表达缺失共 42例，占 8.86% (42/474)；两种及以上蛋白表达缺失共 29例，占 6.12%（29/474）；MLH1，MSH2和 PMS2同时表达缺失率 0.84%（4/474）；MLH1，MSH2， MSH6和 PMS2全部表达缺失率 0.21%(1/474)。MSI-H型胃癌患者淋巴结转移率和脉管侵犯率低于 MSI - L/MSS型胃癌，差异具有统计学意义（χ2=21.65，8.93，均 P＜ 0.05）。而两组患者在性别、年龄、 Borramn分型、Lauren分型、分化程度、浸润深度和远处转移等方面比较，差异均无统计学意义（χ2=0.03～2.79，均 P＞ 0.05）。MSI-H型与 MSI-L/MSS型胃癌患者相比，三年总生存率（overall survival，OS）为 87.52%和 62.68%，差异无统计学意义（χ2=3.64，P＞ 0.05），三年无进展生存率（progression-free survival，PFS）为 75.00%和 57.84%，差异无统计学意义（χ2=3.21，P＞ 0.05）。结论 与 MSI-L/MSS型胃癌相比， MSI-H型胃癌患者淋巴结的转移率低和脉管的侵犯率低，三年 OS和 PFS偏高，提示 MSI-H型胃癌患者有较好的预后。
Abstract:
Objective To investigate the expression of MutL homologue 1(MLH1), MutS homologue 2(MSH2), MutS homologue 6(MSH6) and postmeteorological segregation increased 2 (PMS2) in gastric cancer and their correlation with clinicopathological characteristics and prognosis. Methods 474 cases of gastric cancer tissues diagnosed by the Department of Pathology of the Affiliated Hospital of Chengde Medical College from November 2018 to November 2021 were selected as the study objects. The expression levels of MLH1, MSH2, MSH6 and PMS2 proteins in gastric cancer tissues were detected by immunohistochemistry SP method. According to the expression of these four proteins, gastric cancer tissues were divided into high-frequency microsatellite instability-high (MSI-H) group and low-frequency microsatellite instability-low/microsatellite stability (MSI-L/MSS) group. The clinicopathological characteristics of the two groups were compared. Kaplan-Meier survival analysis was used to compare the prognosis of the two groups. Results Among 474 cases of gastric cancer, 403 cases (85.02%) were MSI-L/MSS type and 71 cases (14.98%) were MSI-H type. Among them, 42 cases (8.86%, 42/474) lost any expression of 4 kinds of mismatch repair proteins (MLH1, MSH2, MSH6, PMS2), 29 cases (6.12%, 29/474) had two or more protein expression deletions. The deletion rate of MLH1, MSH2 and PMS2 was 0.84% (4/474). The deletion rate of MLH1, MSH2, MSH6, PMS2 was 0.21% (1/474). The lymph node metastasis rate and vascular invasion rate of patients with MSI-H gastric cancer were lower than those of patients with MSI-L/MSS gastric cancer, and the difference was statistically significant (χ2=21.65, 8.93, all P<0.05). However, there was no significant difference in gender, age, Borramn type, Lauren type, differentiation, depth of invasion and distant metastasis between the two groups (χ2=0.03～2.79, all P>0.05). Compared with MSI-L/MSS gastric cancer patients, the 3-year overall survival rate (OS) of MSI-H type patients was 87.52% and 62.68%, with no significant difference (χ2=3.64, P>0.05). The 3-year progression free survival (PFS) rates were 75.00% and 57.84%, and the difference was not statistically significant (χ2=3.21, P>0.05). Conclusion Compared with MSI-L/MSS gastric cancer, MSI-H gastric cancer patients have lower lymph node metastasis rate and lower vascular invasion rate, and higher OS and PFS in 3 years, suggesting that MSI-H gastric cancer patients have better prognosis.

参考文献/References:

[1] 李欢 , 郑宝昌 , 陈洁 , 等．微卫星不稳定性、错配修复与胃癌关系的研究进展 [J]．四川解剖学杂志 , 2018, 26(4):165-167. LI Huan, ZHENG Baochang, CHEN Jie, et al. Research progress on relationship among microsatellite instabil-ity, mismatch repair and gastric carcinoma[J]. Sichuan Journal of Anatomy, 2018, 26(4): 165-167.
[2] 朱涛 , 王伟 , 吴和刚．胃癌组织中 FOXP1和 FOXQ1的表达水平与临床病理特征及预后关系 [J].现代检验医学杂志 , 2021, 36(4): 68-73． ZHU Tao, WANG Wei, WU Hegang. Expression of FOXP1 and FOXQ1 in gastric cancer and their relation-ship with clinicopathological features and prognosis[J]. Journal of Modern Laboratory Medicine, 2021, 36(4): 68-73.
[3] 张科 , 王晓光 , 金志明 , 等．胃癌患者组织及血清中 Periostin的表达情况及其意义探讨 [J]．现代检验医学杂志 , 2017, 32（1）：84-86, 90． ZHANG Ke, WANG Xiaoguang, JIN Zhiming, et al. Patients with gastric cancer tissue and serum Periostin expression and its significance[J]. Journal of Modern Laboratory Medicine, 2017, 32(1): 84-86, 90.
[4] WANG Haiyong, DING Yongfeng, CHEN Yanyan, et al. A novel genomic classification system of gastric cancer via integrating multidimensional genomic char-acteristics[J]. Gastric Cancer, 2021, 24(6): 1227-1241.
[5] POLOM K, MARANO L, MARRELLI D, et al. Me-ta-analysis of microsatellite instability in relation to clinicopathological characteristics and overall survival in gastric cancer[J]. The British Journal of Surgery, 2018, 105(3): 159-167.
[6] ZHANG Min, FAN Yibo, CHE Xiaofang, et al. 5-FU-induced upregulation of exosomal PD-L1 causes immunosuppression in advanced gastric cancer pa-tients[J]. Frontiers in Oncology, 2020, 10: 492.
[7] KOUSTAS E, TRIFYLLI E M, SARANTIS P, et al. Immunotherapy as a therapeutic strategy for gastro-intestinal cancer-current treatment options and future perspectives[J]. International Journal of Molecular Sci-ences, 2022, 23(12): 6664.
[8] KWAK Y, SEO A N, LEE H E, et al. Tumor immune response and immunotherapy in gastric cancer[J]. Jour-nal of Pathology and Translational Medicine, 2020, 54(1):20-33..
[9] POLOM K, MARANO L, MARRELLI D, et al. Me-ta-analysis of microsatellite instability in relation to clinicopathological characteristics and overall survival in gastric cancer[J]. The British Journal of Surgery, 2018, 105(3): 159-167.
[10] BANG Y J, KANG Y K, CATENACCI D V, et al. Pem-brolizumab alone or in combination with chemotherapy as first-line therapy for patients with advanced gastric or gastroesophageal junction adenocarcinoma: results from the phase II nonrandomized KEYNOTE-059 study[J]. Gastric Cancer, 2019, 22(4): 828-837.
[11] GUAN Wenlong, MA Yue, CUI Yuehong, et al. The im-pact of mismatch repair status on prognosis of patients with gastric cancer: a multicenter analysis[J]. Frontiers in Oncology, 2021, 11: 712760.
[12] SERRA O, GALáN M, GINESTA M M, et al. Com-parison and applicability of molecular classifications for gastric cancer[J]. Cancer Treatment Reviews, 2019, 77:29-34.
[13] fiORILLO C , LATERZA V , QUERO G , et al. From biology to surgery: One step beyond histology for tai-lored surgical treatments of gastric cancer[J]. Surgical Oncology, 2020, 34(7517): 86-95.
[14] PIETRANTONIO F, MICELI R, RAIMONDI A, et al. Individual patient data meta-analysis of the value of microsatellite instability as a biomarker in gastric cancer[J]. Journal of Clinical Oncology, 2019, 37(35): 3392-3400.

备注/Memo

备注/Memo:
收稿日期：2022-07-17修回日期：2022-12-12
基金项目：2020年承德市科学技术研究与发展计划项目（项目编号： 202006A042）；河北省自然科学基金资助项目（项目编号：H2019406073）。
作者简介：郝美玲（1989-），女，硕士研究生，主治医师，研究方向：胃癌的基础与临床研究， E-mail：15632495450@163.com。
通讯作者：李春辉（1965-），男，博士研究生，主任医师，研究方向：胃癌的基础与临床研究， E-mail：chli612@126.com。

更新日期/Last Update: 2023-03-15