Sun Zhenqiang, Yu Xianbo, Wang Haijiang, Zhang Shuo, Zhao Zeliang, Xu Ruiwei
Department of Gastrointestinal Surgery, Affiliated Tumor Hospital, Xinjiang Medical University, Urumqi, Xinjiang 830011, P.R. China ; Research Laboratory of Disease Genomics, Cancer Research Institute, Central South University, Changsha, Hunan 4170078, P.R. China.
Department of Gastrointestinal Surgery, Affiliated Tumor Hospital, Xinjiang Medical University, Urumqi, Xinjiang 830011, P.R. China.
Exp Ther Med. 2014 Nov;8(5):1416-1422. doi: 10.3892/etm.2014.1927. Epub 2014 Aug 22.
Mismatch repair (MMR) genes play an important role in the occurrence and development of sporadic colorectal cancer; however, the effect of MMR genes on clinicopathological features and prognosis remains unclear. The aim of the present study was to observe the clinical significance of MMR gene expression in sporadic colorectal cancer. Clinicopathological data and postoperative samples from 404 patients with sporadic colorectal cancer were obtained from the Affiliated Tumor Hospital of Xinjiang Medical University. The immunohistochemistry PV-9000 two-step method was performed to measure the protein expression of human mutL homolog 1 (hMLH1), human mutS homolog (hMSH) 2, human postmeiotic segregation increased 2 (hPSM2) and hMSH6. Differences in clinicopathological features, family history and survival time subsequent to surgery between groups with normal and aberrant MMR protein (MMRP) expression were compared. A total of 27.23% of all patients showed aberrant nuclear staining of MMRP. Among the patients with aberrant MMRP expression, a higher proportion of patients showed aberrant expression of more than one type of MMRP than aberrant expression of only one type of MMRP. Aberrant expression of hMLH1/hPSM2 was most commonly observed (29/404). In addition, aberrant MMRP expression in colorectal cancer was indicated predominantly in the right hemicolon. Histological type primarily showed mucinous adenocarcinoma. In addition, with increasing body mass index (BMI), the MMRP deficiency rate was also shown to increase gradually. There was a close association between MMRP expression deficiency and family history of cancer (P<0.05). For TNM stage III patients, the Kaplan-Meier survival curve showed that the aberrant MMRP expression group had a three-year disease-free survival (DFS) rate of 66.67%, which was longer than the DFS rate of the normal group (55.41%), with no statistical difference (P>0.05). In conclusion, the immunohistochemistry PV-9000 two-step method can be used to measure MMRP expression in colorectal cancer. Aberrant MMRP expression is closely correlated with tumor location, histological type, BMI and tumor family history in sporadic colorectal cancer. Aberrant MMRP expression may have an effect on the prognosis of stage III patients.
错配修复(MMR)基因在散发性结直肠癌的发生发展中起重要作用;然而,MMR基因对临床病理特征和预后的影响仍不清楚。本研究的目的是观察MMR基因表达在散发性结直肠癌中的临床意义。从新疆医科大学附属肿瘤医院获取404例散发性结直肠癌患者的临床病理资料和术后样本。采用免疫组织化学PV-9000两步法检测人错配修复蛋白L同源物1(hMLH1)、人错配修复蛋白S同源物(hMSH)2、人减数分裂后分离增加蛋白2(hPSM2)和hMSH6的蛋白表达。比较错配修复蛋白(MMRP)表达正常和异常的组在临床病理特征、家族史及术后生存时间方面的差异。所有患者中共有27.23%表现出MMRP核染色异常。在MMRP表达异常的患者中,表现出一种以上MMRP异常表达的患者比例高于仅表现一种MMRP异常表达的患者。最常观察到hMLH1/hPSM2异常表达(29/404)。此外,结直肠癌中MMRP异常表达主要见于右半结肠。组织学类型主要为黏液腺癌。此外,随着体重指数(BMI)升高,MMRP缺乏率也逐渐升高。MMRP表达缺乏与癌症家族史密切相关(P<0.05)。对于TNM III期患者,Kaplan-Meier生存曲线显示,MMRP异常表达组的三年无病生存率(DFS)为66.67%,长于正常组的DFS率(55.41%),但无统计学差异(P>0.05)。总之,免疫组织化学PV-9000两步法可用于检测结直肠癌中MMRP的表达。散发性结直肠癌中MMRP异常表达与肿瘤位置、组织学类型、BMI及肿瘤家族史密切相关。MMRP异常表达可能对III期患者的预后有影响。