结直肠癌中错配修复基因表达与临床病理及Pgp、GSTπ、TopoⅡ、Ki-67表达的关系研究
| 作者: |
1王露,
1陈思敏,
1赵苏苏,
1章宜芬
1 江苏省中医院病理科，南京 210000 |
| 通讯: |
王露
Email: sea_sky_way@163.com |
| DOI: | 10.3978/j.issn.2095-6959.2016.07.013 |
摘要
目的：探讨结直肠癌错配修复基因(MLH1，PMS2，MSH2，MSH6)免疫组化表达特点及其与临床病理的关系，以及错配修复基因(MLH1，PMS2，MSH2，MSH6)与结直肠癌中P-糖蛋白(Pgp)、谷胱甘肽-S-转移酶(GSTπ)、DNA拓扑异构酶Ⅱ(TopoⅡ)、细胞增殖抗原Ki-67免疫组化表达关系。方法：回顾性分析2014年2月至2015年12月我院收治的93例结直肠癌患者的临床病理资料，采用免疫组织化学法，检测癌组织中错配修复基因(MLH1，PMS2，MSH2，MSH6)、Pgp、GSTπ、TopoⅡ、Ki-67的表达，分析其表达特点。采用多个样本率(或构成比) 的比较(即：R×C表的χ2检验)，分析结直肠癌错配修复基因(MLH1，PMS2，MSH2，MSH6)与临床病理的关系及其与Pgp、GSTπ、TopoⅡ、Ki-67免疫组化表达关系。利用Pearson相关分析法分析MLH1、PMS2、MSH2、MSH6与Ki-67表达相关性。结果：错配修复基因MLH1、PMS2、MSH2、MSH6表达缺失阳性率分别占14.0%、17.2%、10.8%、11.8%，Pgp(−)、Pgp (+)、Pgp (++)、Pgp (+++)表达率分别占3.2%、25.8%、51.6%、19.3%。GSTπ(−)、GSTπ(+)、GSTπ(++)、GSTπ(+++)表达率分别占3.3%、16.7%、56.7%、23.3%。TopoⅡ阴性表达及IV级表达未见，TopoⅡ Ⅰ级、Ⅱ级、Ⅲ级表达率分别占19.3%、77.4%、3.2%。Ki-67表达<10%(+)、10-50%(+)、>50%(+)分别占1.3%、25%、50%。错配修复基因MLH1、PMS2、MSH2、MSH6缺失表达与患者的性别、年龄、病理分化、TNM分期无统计学差异(P>0.05)。MSH2缺失表达与发病部位无统计学差异(P>0.05)。MLH1、PMS2、MSH6基因缺失表达与发病部位有一定差异性(P<0.05)，发生左半结肠的缺失表达阳性率分别为：10.7%、10.7%、7.1%，右半结肠缺失表达阳性率分别为28.6%、35.7%、25%，直肠缺失表达阳性率为5.4%、8.1%、5.4%。MLH1、PMS2、MSH2、MSH6缺失表达与Pgp、GSTπ、TopoⅡ的表达无统计学差异(P>0.05)。MLH1、PMS2、MSH2、MSH6缺失表达与Ki-67表达有一定差异性(P<0.05)，Ki-67<10%(+)的MLH1、PMS2、MSH2、MSH6缺失表达率为62.5%，Ki-67 10%~50%(+)的MLH1、PMS2、MSH2、MSH6缺失表达率分别为21.1%、0、10.5%、5.3%，Ki-67 >50%(+)的MLH1、PMS2、MSH2、MSH6缺失表达率分别为6.1%、4.1%、8.2%、6.1%。MLH1、PMS2、MSH2、MSH6缺失表达与Ki-67表达呈负相关(相关系数分别为r=−0.969、r=−0.464、r=−0.143、r=−0.344，P<0.05)。结论：错配修复基因MLH1、PMS2、MSH6基因缺失表达发生右半结肠几率相对较高，其次依次是左半结肠、直肠。MLH1、PMS2、MSH2、MSH6缺失表达与Ki-67表达呈负相关。
关键词：
错配修复基因
Pgp；GSTπ
TopoⅡ
Ki-67
结直肠癌
The research on the relationship between the expression of the mismatch repair genes and the clinicopathology and the expression of Pgp, GSTπ, TopoⅡ, Ki-67 in colorectal cancer
CorrespondingAuthor: WANG Lu Email: sea_sky_way@163.com
DOI: 10.3978/j.issn.2095-6959.2016.07.013
Abstract
Objective: To investigate the immunohistochemical expression characteristics of mismatch repair genes (MLH1, PMS2, MSH2, MSH6), and the relationship with clinicopathology features, and the correlation between the immunohistochemical expression of P-glycoprotein (Pgp), glutathione -S- transferase (GSTπ), DNA topoisomerase Ⅱ (TopoⅡ), cell proliferation antigen Ki-67 and those four mismatch repair genes in colorectal cancer. Methods: The clinicopathology characteristics of 93 cases of colorectal cancer patients in our hospital from 2014/2 to 2015/12 were analyzed retrospectively. Expression features of mismatch repair genes (MLH1, PMS2, MSH2, MSH6), Pgp, GSTπ, TopoⅡ, Ki-67 determined by immunohistochemical staining were analyzed. Then we used a plurality of sample rate (or constituent ratio) comparisons (i.e., χ2 test with R×C table) to analyze the relationship between immunohistochemical expression of mismatch repair genes (MLH1, PMS2, MSH2, MSH6) and Pgp, GSTπ, TopoⅡ, Ki-67 in colorectal cancer. Pearson correlation analyses were used to analyze the correlation of the expression between mismatch repair genes (MLH1, PMS2, MSH2, MSH6) and Ki-67. Results: The missing expression rate of mismatch repair genes MLH1, PMS2, MSH2, MSH6 were 14.0%, 17.2%, 10.8%, 11.8%, respectively. The expression rate of Pgp(−), Pgp (+), Pgp (++), Pgp (+++) each accounted for 3.2%, 25.8%, 51.6%, 19.3%. The expression rate of GSTπ (−), GSTπ (+), GSTπ (++), GSTπ (+++) accounted for 3.3%, 16.7%, 56.7%, 23.3%. TopoⅡhad no negative and IV level expression, TopoⅡ Ⅰ level, Ⅱ level, Ⅲ level accounted for 19.3%, 77.4%, 3.2%. The expression rate of Ki-67 <10% (+), 10%~50% (+), >50% (+) accounted for 1.3%, 25%, 50%, separately. There was no statistically significant difference (P>0.05) between missing expression of mismatch repair genes (MLH1, PMS2, MSH2, MSH6) and gender, age, histological differentiation and TNM staging. There was also no significant difference (P>0.05) between MSH2 missing expression and the lesion location. However, there was some difference (P<0.05) between MLH1, PMS2, MSH6 missing expression and the lesion location. The missing expression of MLH1, PMS2, MSH6 occurred in left colon was 10.7%, 10.7%, 7.1%, while that in the right colon was 28.6%, 35.7%, 25%, in rectum was 5.4%, 8.1%, 5.4%, respectively. There was no statistically significant difference (P>0.05) between MLH1, PMS2, MSH2, MSH6 missing expression and Pgp, GSTπ, TopoⅡ expression. Nevertheless, the differences existed between MLH1, PMS2, MSH2, MSH6 missing expression and Ki-67 expression (P<0.05). The MLH1, PMS2, MSH2, MSH6 missing expression rate of Ki-67 <10% (+) was 62.5%. Those of Ki-67 10%~50% (+) were 21.1%, 0, 10.5%, 5.3%. And those of Ki-67 >50% (+) were 6.1%, 4.1%, 8.2%, 6.1%, respectively. MLH1, PMS2, MSH2, MSH6 missing expression and Ki-67 expression was negatively correlated (correlation coefficient r=−0.969, r=−0.464, r=−0.143, r=−0.344, P<0.05). Conclusion: The missing expression of mismatch repair genes (MLH1, PMS2, MSH2, MSH6) relatively had high probability of occurrence of the right colon, followed by left colon, rectum, successively. The missing expression of those genes and the expression of Ki-67 was negatively correlated.