Relationship Between The Expressions of hMLH1 and hMSH2 Protein and Clinicopathological Features and Prognosis of Hereditary Nonpolyposis Colorectal Cancer_CHINESE JOURNAL OF BASES AND CLINICS IN GENERAL SURGERY

Authors：

MENG Jin ,  LI Xiaoxia , ZHAO Meng , TANG Yuanxin , SUN Gongping , LI Xin , YAN Yifei.

Department of Gastrointestinal Surgery， The Fourth Affiliated Hospital， China Medical University， Shenyang 110032， Liaoning Province， China;

Corresponding author：

LI Xiaoxia, Email: LXX555999@yahoo.com.cn

Keywords：

Hereditary nonpolyposis colorectal cancer; Mismatch repair gene; Immunohistochemistry

Video：

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Objective 　To investigate the relationship between the expressions of mismatch repair （MMR） genes （include hMLH1 and hMSH2） and clinicopathological features and prognosis of hereditary nonpolyposis colorectal cancer （HNPCC）.
Methods 　Immunohistochemistry method （Elivision-two step） was used to test expressions of hMLH1 and hMSH2 proteins （both hMLH1 and hMSH2 protein-positive delimited as MMR protein-positive） in 48 patients with HNPCC
according to revised Bethesda guidelines， and analyzed the relationship between the expression of MMR protein and clinicopathological features and prognosis of HNPCC.
Results 　Loss rate of hMLH1 protein （20.83%，10/48） was signi-ficantly higher than that of hMSH2 protein （8.33%，4/48）， Ρ＜0.05， and positive expression rate of MMR protein was 70.83% （34/48）. Expression of MMR protein was related with tumor infiltration depth （Ρ＜0.05）. Survival rate of patients with expression and without expression of MMR protein was 85.29% （29/34） and 85.71% （12/14）， respectively， the survival curves of them didn’t significantly differed from each other （Ρ＞0.05）.
Conclusions 　Loss rate of hMLH1 protein is higher than that of hMSH2 protein. Expre ssions of hMLH1 and hMSH2 protein are related with tumor infiltration depth， but not related with prognosis.

Citation： MENG Jin,LI Xiaoxia,ZHAO Meng,TANG Yuanxin,SUN Gongping,LI Xin,YAN Yifei.. Relationship Between The Expressions of hMLH1 and hMSH2 Protein and Clinicopathological Features and Prognosis of Hereditary Nonpolyposis Colorectal Cancer. CHINESE JOURNAL OF BASES AND CLINICS IN GENERAL SURGERY, 2013, 20(1): 66-70. doi: Copy

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16.	Scartozzi M， Bianchi F， Rosati S， et al. Mutations of hMLH1 and hMSH2 in patients with suspected hereditary nonpolyposis colorectal cancer： correlation with microsatellite instability and abnormalities of mismatch repair protein expression[J]. J Clin Oncol， 2002， 20(5)： 1203-1208.
17.	Ottenhof NA， Morsink FH， Ten Kate F， et al. Multivariate analysis of immunohistochemical evaluation of protein expression in pancreatic ductal adenocarcinoma reveals prognostic significance for persistent Smad4 expression only[J]. Cell Oncol (Dordr)， 2012， 35(2)： 119-126.
18.	Whitehall V， Leggett B. Microsatellite instability： detection and management in sporadic colorectal cancer[J]. J Gastroenterol Hepatol， 2011， 26(12)： 1697-1699.
19.	Hendriks YM， de Jong AE， Morreau H， et al. Diagnostic appro-ach and management of Lynch syndrome (hereditary nonpolyposis colorectal carcinoma)： a guide for clinicians[J]. CA Cancer J Clin， 2006， 56(4)： 213-225.
20.	袁瑛，郑树. 可疑遗传性非息肉病性结直肠癌的hMLH1和hMSH2基因的突变研究[J]. 中华医学杂志， 1999， 79(5)： 346-348.
21.	Han HJ， Yuan Y， Ku JL， et al. Germline mutations of hMLH1 and hMSH2 genes in Korean hereditary nonpolyposis colorectal cancer[J]. J Natl Cancer Inst， 1996， 88(18)： 1317-1319.
22.	Pino MS， Chung DC. Microsatellite instability in the managementof colorectal cancer[J]. Expert Rev Gastroenterol Hepatol， 2011，5(3)： 385-399.
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24.	Shin KH， Shin JH， Kim JH， et al. Mutational analysis of promo-ters of mismatch repair genes hMSH2 and hMLH1 in hereditary nonpolyposis colorectal cancer and early onset colorectal cancer patients：identiﬁcation of three novel germ-line mutations in promoter of the hMSH2 gene[J]. Cancer Res， 2002， 62(1)： 38-42.
25.	Lynch HT， Smyrk T. Hereditary nonpolyposis colorectal cancer (Lynch syndrome). An updated review[J]. Cancer， 1996， 78(6)：1149-1167.

1. Lynch HT， Lynch PM， Lanspa SJ， et al. Review of the lynch syndrome： history， molecular genetics， screening， differential diagnosis， and medicolegal ramifications[J]. Clin Genet， 2009，76(1)： 1-18.
2. Bronner CE， Baker SM， Morrison PT， et al. Mutation in the DNAmismatch repair gene homologue hMLH1 is associated with here-ditary non-polyposis colon cancer[J]. Nature， 1994， 368(6468)：258-261.
3. Papadopoulos N， Nicolaides NC， Wei YF， et al. Mutation of a mutL homolog in hereditary colon cancer[J]. Science， 1994， 263(5153)： 1625-1629.
4. Lindblom A， Tannergård P， Werelius B， et al. Genetic mapping of a second locus predisposing to hereditary non-polyposis colon cancer[J]. Nat Genet， 1993， 5(3)： 279-282.
5. Peltomäki P， Aaltonen LA， Sistonen P， et al. Genetic mapping of a locus predisposing to human colorectal cancer[J]. Science， 1993， 260(5109)： 810-812.
6. Fishel R， Lescoe MK， Rao MR， et al. The human mutator gene homolog MSH2 and its association with hereditary nonpolyposis colon cancer[J]. Cell， 1993， 75(5)： 1027-1038.
7. Leach FS， Nicolaides NC， Papadopoulos N， et al. Mutations of a mutS homolog in hereditary nonpolyposis colorectal cancer[J]. Cell， 1993， 75(6)： 1215-1225.
8. Hendriks YM， Wagner A， Morreau H， et al. Cancer risk in hered-itary nonpolyposis colorectal cancer due to MSH6 mutations： imp-act on counseling and surveillance[J]. Gastroenterology， 2004， 127(1)： 17-25.
9. Nicolaides NC， Papadopoulos N， Liu B， et al. Mutations of two PMS homologues in hereditary nonpolyposis colon cancer[J]. Nature， 1994， 371(6492)： 75-80.
10. Wagner A， Tops C， Wijnen JT， et al. Genetic testing in hereditarynon-polyposis colorectal cancer families with a MSH2， MLH1， orMSH6 mutation[J]. J Med Genet， 2002， 39(11)： 833-837.
11. Ricciardiello L， Boland CR. Lynch syndrome (hereditary nonpoly-posis colorectal cancer)： current concepts and approaches to management[J]. Curr Gastroenterol Rep， 2005， 7(5)： 412-420.
12. Lynch HT， de la Chapelle A. Hereditary colorectal cancer[J]. N Engl J Med， 2003， 348(10)： 919-932.
13. 李晓霞，唐元新，孙公平，等. 中国东北地区遗传性非息肉病性结直肠癌家系肠外肿瘤谱特点分析[J]. 中国普外基础与临床杂志， 2012， 19(3)：288-291.
14. Umar A， Boland CR， Terdiman JP， et a1. Revised Bethesda Guid-elines for hereditary nonpolyposis colorectal cancer (Lynch synd-rome) and microsatellite instability[J]. J Natl Cancer Inst， 2004，96(4)：261-268.
15. Vasen HF， Watson P， Mecklin JP， et al. New clinical criteria forhereditary nonpolyposis colorectal cancer (HNPCC， Lynch synd-rome) proposed by the International Collaborative group on HNPCC[J]. Gastroenterology， 1999， 116(6)： 1453-1456.
16. Scartozzi M， Bianchi F， Rosati S， et al. Mutations of hMLH1 and hMSH2 in patients with suspected hereditary nonpolyposis colorectal cancer： correlation with microsatellite instability and abnormalities of mismatch repair protein expression[J]. J Clin Oncol， 2002， 20(5)： 1203-1208.
17. Ottenhof NA， Morsink FH， Ten Kate F， et al. Multivariate analysis of immunohistochemical evaluation of protein expression in pancreatic ductal adenocarcinoma reveals prognostic significance for persistent Smad4 expression only[J]. Cell Oncol (Dordr)， 2012， 35(2)： 119-126.
18. Whitehall V， Leggett B. Microsatellite instability： detection and management in sporadic colorectal cancer[J]. J Gastroenterol Hepatol， 2011， 26(12)： 1697-1699.
19. Hendriks YM， de Jong AE， Morreau H， et al. Diagnostic appro-ach and management of Lynch syndrome (hereditary nonpolyposis colorectal carcinoma)： a guide for clinicians[J]. CA Cancer J Clin， 2006， 56(4)： 213-225.
20. 袁瑛，郑树. 可疑遗传性非息肉病性结直肠癌的hMLH1和hMSH2基因的突变研究[J]. 中华医学杂志， 1999， 79(5)： 346-348.
21. Han HJ， Yuan Y， Ku JL， et al. Germline mutations of hMLH1 and hMSH2 genes in Korean hereditary nonpolyposis colorectal cancer[J]. J Natl Cancer Inst， 1996， 88(18)： 1317-1319.
22. Pino MS， Chung DC. Microsatellite instability in the managementof colorectal cancer[J]. Expert Rev Gastroenterol Hepatol， 2011，5(3)： 385-399.
23. Dieumegard B， Grandjouan S， Sabourin JC， et al. Extensive molecular screening for hereditary non-polyposis colorectal cancer[J]. Br J Cancer， 2000， 82(4)： 871-880.
24. Shin KH， Shin JH， Kim JH， et al. Mutational analysis of promo-ters of mismatch repair genes hMSH2 and hMLH1 in hereditary nonpolyposis colorectal cancer and early onset colorectal cancer patients：identiﬁcation of three novel germ-line mutations in promoter of the hMSH2 gene[J]. Cancer Res， 2002， 62(1)： 38-42.
25. Lynch HT， Smyrk T. Hereditary nonpolyposis colorectal cancer (Lynch syndrome). An updated review[J]. Cancer， 1996， 78(6)：1149-1167.

CHINESE JOURNAL OF BASES AND CLINICS IN GENERAL SURGERY

Relationship Between The Expressions of hMLH1 and hMSH2 Protein and Clinicopathological Features and Prognosis of Hereditary Nonpolyposis Colorectal Cancer

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