Expression of hMLH1, hMSH2 or hMSH6 in Sporadic Colorectal Cancer and Relationship of It's Expression to Clinicopathologic Parameters_CHINESE JOURNAL OF BASES AND CLINICS IN GENERAL SURGERY

Authors：

 YUPeng-fei ¹ ,  GUGuo-li ¹ , WEIXue-ming ¹ , LIMing ² , GUJin ²

1. Department of General Surgery, Air Force General Hospital, Air Force Clinical College of Anhui Medical University, Beijing 100142, China;
2. Department of Colorectal Surgery, Beijing Cancer Hospital, Beijing 100142, China;

Corresponding author：

GUGuo-li, Email: kzggl@163.com

Keywords：

Mismatch repair gene; Sporadic colorectal cancer; Lynch syndrome

DOI：

10.7507/1007-9424.20150153

Video：

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Objective To detect the expression of hMLH1, hMSH2 or hMSH6 protein in sporadic colorectal carcinoma (SCRC) and analyze the relationship of its expression to clinicopathologic parameters of patients with SCRC. Methods Two hundred and sixty-three patients with SCRC were studied, who underwent surgery in the Department of General Surgery, the Air Force General Hospital; and the Department of Colorectal Surgery, Beijing Cancer Hospital from March 2008 to March 2012. All the patients were diagnosed by histological examination without chemoradiotherapy before operation. Immunohistochemistry was used to detect the hMLH1, hMSH2 or hMSH6 protein expression in the tumor tissues from 263 cases of SCRC. The relationship of its expression to clinicopathologic parameters was analyzed. Results The loss rates of hMLH1, hMSH2, and hMSH6 expressions in the tumor tissues from 263 patients with SCRC were 13.3% (35/263), 12.2% (32/263), and 28.9% (76/263), respectively. The loss rates of hMLH1/hMSH2, hMLH1/ hMSH6, hMSH2/hMSH6, and hMLH1/hMSH2/hMSH6 expressions were 3.4% (9/263), 10.2% (27/263), 6.8% (18/263), and 3.4% (9/263) corresponding. The loss rate of hMLH1 expression in the high differentiated adenocarcinoma tissues was significantly higher than that of the moderate to low differentiated adenocarcinoma or mucous carcinomas tissues (P < 0.01). The loss rate of hMLH2 expression in the tissues of tumor size more than 5 cm was significantly higher than that in the tissues of tumor size less than 5 cm (P < 0.05). The loss rate of hMSH6 expression in the male patient was significantly higher than that of the female patient (P < 0.01) and which in the tumor tissues of less lymph node metastasis was significantly higher than that in the tissues of the more lymph node metastasis (P < 0.01). Conclusions The hMLH1, hMSH2, or hMSH6 gene expression deletion is common in SCRC and the relation with the clinical pathology of SCRC is obviously different from Lynch syndrome. Therefore, the effects of hMLH1, hMSH2, and hMSH6 expressions on the development, invasion, and metastasis of SCRC are different from Lynch syndrome too.

Citation： YUPeng-fei, GUGuo-li, WEIXue-ming, LIMing, GUJin. Expression of hMLH1, hMSH2 or hMSH6 in Sporadic Colorectal Cancer and Relationship of It's Expression to Clinicopathologic Parameters. CHINESE JOURNAL OF BASES AND CLINICS IN GENERAL SURGERY, 2015, 22(5): 581-585. doi: 10.7507/1007-9424.20150153 Copy

1.	Iacopetta B, Grieu F, Amanuel B. Microsatellite instability in colorectal cancer. Asia Pac J Clin Oncol, 2010, 6(4):260-269.
2.	Jacob S, Praz F. DNA mismatch repair defects:role in colorectal carcinogenesis. Biochimie, 2002, 84(1):27-47.
3.	孟金, 李晓霞, 赵萌, 等.遗传性非息肉病性结直肠癌hMLH1和hMSH2蛋白表达与其临床病理特征及预后的关系.中国普外基础与临床杂志, 2013, 20(1):66-70.
4.	顾国利, 王石林, 魏学明, 等. COX-2、β-cat、MMP-7表达与遗传性非息肉病性大肠癌特殊侵袭转移行为的关系.世界华人消化杂志, 2009, 17(2):151-157.
5.	Ohrling K, Edler D, Hallström M, et al. Mismatch repair protein expression is an independent prognostic factor in sporadic colorectal cancer. Acta Oncol, 2010, 49(6):797-804.
6.	Youn CK, Cho HJ, Kim SH, et al. Bcl-2 expression suppresses mismatch repair activity through inhibition of E2F transcriptional activity. Nat Cell Biol, 2005, 7(2):137-147.
7.	Park IJ, Kim HC, Kim JS, et al. Correlation between hMLH1/hMSH2 and p53 protein expression in sporadic colorectal cancer. Hepatogastroenterology, 2005, 52(62):450-454.
8.	徐俊荣, 宋瑛.林奇综合征的诊治进展.胃肠病学和肝病学杂志, 2010, 19(10):956-959.
9.	Lindor NM, Burgart LJ, Leontovich O, et al. Immunohistochemistry versus microsatellite instability testing in phenotyping colorectal tumors. J Clin Oncol, 2002, 20(4):1043-1048.
10.	Gu GL, Zhu XQ, Wei XM, et al. Epithelial-mesenchymal transition in colorectal cancer tissue of patients with Lynch syndrome. World J Gastroenterol, 2014, 20(1):250-257.
11.	Huang YQ, Yuan Y, Ge WT, et al. Comparative features of colorectal and gastric cancers with microsatellite instability in Chinese patients. J Zhejiang Univ Sci B, 2010, 11(9):647-653.
12.	Kaur G, Masoud A, Raihan N, et al. MLH1 promoter methylation, diet, and life style factors in mismatch repair deficient colorectal cancer patients from EPIC-Norfolk. Nutr Cancer, 2011, 63(7):1000-1010.
13.	项芳芳, 毛高平.错配修复蛋白hMLH1、hMSH2在大肠息肉和散发性大肠癌中的表达差异.中华临床医师杂志:电子版, 2012, 6(15):4280-4284.
14.	王瑜, 童晶, 杨磊, 等.可疑的遗传性非息肉病性大肠癌hMLH1和hMSH2蛋白表达.实用医学杂志, 2014, 30(13):2061-2064.
15.	陈涛, 严立.错配修复基因hMSH2和hMLH1在结直肠癌组织中的表达及临床意义.中国肿瘤临床, 2013, 40(12):710-713.
16.	卢晓晔, 罗惠莉, 覃莉.散发性结直肠癌组织中hMSH2和hMLH1的表达及其意义.广东医学, 2011, 32(8):1018-1020.
17.	Plaschke J, Kruppa C, Tischler R, et al. Sequence analysis of the mismatch repair gene hMSH6 in the germline of patients with familial and sporadic colorectal cancer. Int J Cancer, 2000, 85(5):606-613.
18.	Sidelnikov E, Bostick RM, Flanders WD, et al. Colorectal mucosal expression of MSH2 as a potential biomarker of risk for colorectal neoplasms. Cancer Epidemiol Biomarkers Prev, 2009, 18(11):2965-2973.
19.	陈玉芳, 周林艳, 万美珍, 等. hMLH1、hMSH2、COX-2蛋白在散发性大肠癌的表达及意义.长治医学院学报, 2014, 30(4):263-266, 267.
20.	林武华, 孙念绪, 张青平.散发性结直肠癌微卫星不稳定性与hMSH3和hMSH6基因突变的研究.武警医学, 2001, 12(7):392-395.
21.	宋玉芳, 赵亚双.错配修复基因hMSH6及与肿瘤关系的研究进展.现代肿瘤医学, 2007, 15(9):1336-1339.
22.	刘玮, 凌志强, 毛伟敏. hMSH6基因多态与肿瘤易感性.国际肿瘤学杂志, 2011, 38(4):243-245.
23.	于显博, 王海江, 孙振强, 等.散发性结直肠癌患者错配修复基因蛋白表达水平及其临床意义.中国全科医学, 2014, 17(8):883-887.
24.	Molaei M, Mansoori BK, Ghiasi S, et al. Colorectal cancer in Iran:immunohistochemical profiles of four mismatch repair proteins. Int J Colorectal Dis, 2010, 25(1):63-69.
25.	Iacopetta B. Are there two sides to colorectal cancer? Int J Cancer, 2002, 101(5):403-408.
26.	Parj HW, Chang HJ, Park S, et al. Absence of hMLH1 or hMSH2 expression as a stage-dependent prognostic factor in sporadic colorectal cancers. Ann Surg Oncol, 2010, 17(11):2839-2846.

1. Iacopetta B, Grieu F, Amanuel B. Microsatellite instability in colorectal cancer. Asia Pac J Clin Oncol, 2010, 6(4):260-269.
2. Jacob S, Praz F. DNA mismatch repair defects:role in colorectal carcinogenesis. Biochimie, 2002, 84(1):27-47.
3. 孟金, 李晓霞, 赵萌, 等.遗传性非息肉病性结直肠癌hMLH1和hMSH2蛋白表达与其临床病理特征及预后的关系.中国普外基础与临床杂志, 2013, 20(1):66-70.
4. 顾国利, 王石林, 魏学明, 等. COX-2、β-cat、MMP-7表达与遗传性非息肉病性大肠癌特殊侵袭转移行为的关系.世界华人消化杂志, 2009, 17(2):151-157.
5. Ohrling K, Edler D, Hallström M, et al. Mismatch repair protein expression is an independent prognostic factor in sporadic colorectal cancer. Acta Oncol, 2010, 49(6):797-804.
6. Youn CK, Cho HJ, Kim SH, et al. Bcl-2 expression suppresses mismatch repair activity through inhibition of E2F transcriptional activity. Nat Cell Biol, 2005, 7(2):137-147.
7. Park IJ, Kim HC, Kim JS, et al. Correlation between hMLH1/hMSH2 and p53 protein expression in sporadic colorectal cancer. Hepatogastroenterology, 2005, 52(62):450-454.
8. 徐俊荣, 宋瑛.林奇综合征的诊治进展.胃肠病学和肝病学杂志, 2010, 19(10):956-959.
9. Lindor NM, Burgart LJ, Leontovich O, et al. Immunohistochemistry versus microsatellite instability testing in phenotyping colorectal tumors. J Clin Oncol, 2002, 20(4):1043-1048.
10. Gu GL, Zhu XQ, Wei XM, et al. Epithelial-mesenchymal transition in colorectal cancer tissue of patients with Lynch syndrome. World J Gastroenterol, 2014, 20(1):250-257.
11. Huang YQ, Yuan Y, Ge WT, et al. Comparative features of colorectal and gastric cancers with microsatellite instability in Chinese patients. J Zhejiang Univ Sci B, 2010, 11(9):647-653.
12. Kaur G, Masoud A, Raihan N, et al. MLH1 promoter methylation, diet, and life style factors in mismatch repair deficient colorectal cancer patients from EPIC-Norfolk. Nutr Cancer, 2011, 63(7):1000-1010.
13. 项芳芳, 毛高平.错配修复蛋白hMLH1、hMSH2在大肠息肉和散发性大肠癌中的表达差异.中华临床医师杂志:电子版, 2012, 6(15):4280-4284.
14. 王瑜, 童晶, 杨磊, 等.可疑的遗传性非息肉病性大肠癌hMLH1和hMSH2蛋白表达.实用医学杂志, 2014, 30(13):2061-2064.
15. 陈涛, 严立.错配修复基因hMSH2和hMLH1在结直肠癌组织中的表达及临床意义.中国肿瘤临床, 2013, 40(12):710-713.
16. 卢晓晔, 罗惠莉, 覃莉.散发性结直肠癌组织中hMSH2和hMLH1的表达及其意义.广东医学, 2011, 32(8):1018-1020.
17. Plaschke J, Kruppa C, Tischler R, et al. Sequence analysis of the mismatch repair gene hMSH6 in the germline of patients with familial and sporadic colorectal cancer. Int J Cancer, 2000, 85(5):606-613.
18. Sidelnikov E, Bostick RM, Flanders WD, et al. Colorectal mucosal expression of MSH2 as a potential biomarker of risk for colorectal neoplasms. Cancer Epidemiol Biomarkers Prev, 2009, 18(11):2965-2973.
19. 陈玉芳, 周林艳, 万美珍, 等. hMLH1、hMSH2、COX-2蛋白在散发性大肠癌的表达及意义.长治医学院学报, 2014, 30(4):263-266, 267.
20. 林武华, 孙念绪, 张青平.散发性结直肠癌微卫星不稳定性与hMSH3和hMSH6基因突变的研究.武警医学, 2001, 12(7):392-395.
21. 宋玉芳, 赵亚双.错配修复基因hMSH6及与肿瘤关系的研究进展.现代肿瘤医学, 2007, 15(9):1336-1339.
22. 刘玮, 凌志强, 毛伟敏. hMSH6基因多态与肿瘤易感性.国际肿瘤学杂志, 2011, 38(4):243-245.
23. 于显博, 王海江, 孙振强, 等.散发性结直肠癌患者错配修复基因蛋白表达水平及其临床意义.中国全科医学, 2014, 17(8):883-887.
24. Molaei M, Mansoori BK, Ghiasi S, et al. Colorectal cancer in Iran:immunohistochemical profiles of four mismatch repair proteins. Int J Colorectal Dis, 2010, 25(1):63-69.
25. Iacopetta B. Are there two sides to colorectal cancer? Int J Cancer, 2002, 101(5):403-408.
26. Parj HW, Chang HJ, Park S, et al. Absence of hMLH1 or hMSH2 expression as a stage-dependent prognostic factor in sporadic colorectal cancers. Ann Surg Oncol, 2010, 17(11):2839-2846.

CHINESE JOURNAL OF BASES AND CLINICS IN GENERAL SURGERY

Expression of hMLH1, hMSH2 or hMSH6 in Sporadic Colorectal Cancer and Relationship of It's Expression to Clinicopathologic Parameters

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