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, 李曉霞, 趙萌, 等.遺傳性非息肉病性結直腸癌hMLH1和hMSH2蛋白表達與其臨床病理特征及預后的關系.中國普外基礎與臨床雜志, 2013, 20(1):66-70.
4.	顧國利, 王石林, 魏學明, 等. COX-2、β-cat、MMP-7表達與遺傳性非息肉病性大腸癌特殊侵襲轉移行為的關系.世界華人消化雜志, 2009, 17(2):151-157.
5.	Ohrling K, Edler D, Hallstr?m 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.	徐俊榮, 宋瑛.林奇綜合征的診治進展.胃腸病學和肝病學雜志, 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.	項芳芳, 毛高平.錯配修復蛋白hMLH1、hMSH2在大腸息肉和散發性大腸癌中的表達差異.中華臨床醫師雜志:電子版, 2012, 6(15):4280-4284.
14.	王瑜, 童晶, 楊磊, 等.可疑的遺傳性非息肉病性大腸癌hMLH1和hMSH2蛋白表達.實用醫學雜志, 2014, 30(13):2061-2064.
15.	陳濤, 嚴立.錯配修復基因hMSH2和hMLH1在結直腸癌組織中的表達及臨床意義.中國腫瘤臨床, 2013, 40(12):710-713.
16.	盧曉曄, 羅惠莉, 覃莉.散發性結直腸癌組織中hMSH2和hMLH1的表達及其意義.廣東醫學, 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.	陳玉芳, 周林艷, 萬美珍, 等. hMLH1、hMSH2、COX-2蛋白在散發性大腸癌的表達及意義.長治醫學院學報, 2014, 30(4):263-266, 267.
20.	林武華, 孫念緒, 張青平.散發性結直腸癌微衛星不穩定性與hMSH3和hMSH6基因突變的研究.武警醫學, 2001, 12(7):392-395.
21.	宋玉芳, 趙亞雙.錯配修復基因hMSH6及與腫瘤關系的研究進展.現代腫瘤醫學, 2007, 15(9):1336-1339.
22.	劉瑋, 凌志強, 毛偉敏. hMSH6基因多態與腫瘤易感性.國際腫瘤學雜志, 2011, 38(4):243-245.
23.	于顯博, 王海江, 孫振強, 等.散發性結直腸癌患者錯配修復基因蛋白表達水平及其臨床意義.中國全科醫學, 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, 李曉霞, 趙萌, 等.遺傳性非息肉病性結直腸癌hMLH1和hMSH2蛋白表達與其臨床病理特征及預后的關系.中國普外基礎與臨床雜志, 2013, 20(1):66-70.
4. 顧國利, 王石林, 魏學明, 等. COX-2、β-cat、MMP-7表達與遺傳性非息肉病性大腸癌特殊侵襲轉移行為的關系.世界華人消化雜志, 2009, 17(2):151-157.
5. Ohrling K, Edler D, Hallstr?m 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. 徐俊榮, 宋瑛.林奇綜合征的診治進展.胃腸病學和肝病學雜志, 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. 項芳芳, 毛高平.錯配修復蛋白hMLH1、hMSH2在大腸息肉和散發性大腸癌中的表達差異.中華臨床醫師雜志:電子版, 2012, 6(15):4280-4284.
14. 王瑜, 童晶, 楊磊, 等.可疑的遺傳性非息肉病性大腸癌hMLH1和hMSH2蛋白表達.實用醫學雜志, 2014, 30(13):2061-2064.
15. 陳濤, 嚴立.錯配修復基因hMSH2和hMLH1在結直腸癌組織中的表達及臨床意義.中國腫瘤臨床, 2013, 40(12):710-713.
16. 盧曉曄, 羅惠莉, 覃莉.散發性結直腸癌組織中hMSH2和hMLH1的表達及其意義.廣東醫學, 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. 陳玉芳, 周林艷, 萬美珍, 等. hMLH1、hMSH2、COX-2蛋白在散發性大腸癌的表達及意義.長治醫學院學報, 2014, 30(4):263-266, 267.
20. 林武華, 孫念緒, 張青平.散發性結直腸癌微衛星不穩定性與hMSH3和hMSH6基因突變的研究.武警醫學, 2001, 12(7):392-395.
21. 宋玉芳, 趙亞雙.錯配修復基因hMSH6及與腫瘤關系的研究進展.現代腫瘤醫學, 2007, 15(9):1336-1339.
22. 劉瑋, 凌志強, 毛偉敏. hMSH6基因多態與腫瘤易感性.國際腫瘤學雜志, 2011, 38(4):243-245.
23. 于顯博, 王海江, 孫振強, 等.散發性結直腸癌患者錯配修復基因蛋白表達水平及其臨床意義.中國全科醫學, 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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