• 中國醫(yī)科大學附屬第四醫(yī)院胃腸外科(遼寧沈陽 110032);

目的  探討錯配修復(MMR)基因hMLH1和hMSH2的蛋白表達與遺傳性非息肉病性結直腸癌(HNPCC)臨床病理特征及預后的關系。
方法  應用免疫組化方法(Elivision-兩步法)檢測48例符合修訂后的 《Bethesda指南》 的HNPCC患者中hMLH1和hMSH2蛋白的表達情況,并定義兩者同時表達陽性為MMR蛋白表達,分析其表達與HNPCC臨床病理特征及預后的關系。
結果  hMLH1蛋白的表達缺失率為20.83(10/48),高于hMSH2蛋白的表達缺失率(8.33%,4/48),Ρ<0.05; MMR蛋白的表達陽性率為70.83%(34/48)。MMR蛋白表達與腫瘤的浸潤深度相關(Ρ<0.05)。MMR蛋白表達缺失與表達正常者的總生存率分別為85.71%(12/14)和85.29%(29/34),兩者生存曲線比較差異無統(tǒng)計學意義(Ρ>0.05)。
結論  hMLH1蛋白的表達缺失率高于hMSH2蛋白,hMLH1和hMSH2蛋白表達缺失與腫瘤的浸潤深度相關,與患者的預后無關。

引用本文: 孟金,李曉霞,趙萌,唐元新,孫公平,李鑫,閆一飛. 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. doi: 復制

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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. 李曉霞, 唐元新, 孫公平, 等. 中國東北地區(qū)遺傳性非息肉病性結直腸癌家系腸外腫瘤譜特點分析[J]. 中國普外基礎與臨床雜志, 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, 鄭樹. 可疑遺傳性非息肉病性結直腸癌的hMLH1和hMSH2基因的突變研究[J]. 中華醫(yī)學雜志, 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:identi?cation 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. 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. 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. 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. 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. 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. 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. 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. 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. 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. 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. 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. 12. Lynch HT, de la Chapelle A. Hereditary colorectal cancer[J]. N Engl J Med, 2003, 348(10): 919-932.
  13. 13. 李曉霞, 唐元新, 孫公平, 等. 中國東北地區(qū)遺傳性非息肉病性結直腸癌家系腸外腫瘤譜特點分析[J]. 中國普外基礎與臨床雜志, 2012, 19(3):288-291.
  14. 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. 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. 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. 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. 18. Whitehall V, Leggett B. Microsatellite instability: detection and management in sporadic colorectal cancer[J]. J Gastroenterol Hepatol, 2011, 26(12): 1697-1699.
  19. 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. 20. 袁瑛, 鄭樹. 可疑遺傳性非息肉病性結直腸癌的hMLH1和hMSH2基因的突變研究[J]. 中華醫(yī)學雜志, 1999, 79(5): 346-348.
  21. 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. 22. Pino MS, Chung DC. Microsatellite instability in the managementof colorectal cancer[J]. Expert Rev Gastroenterol Hepatol, 2011,5(3): 385-399.
  23. 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. 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:identi?cation of three novel germ-line mutations in promoter of the hMSH2 gene[J]. Cancer Res, 2002, 62(1): 38-42.
  25. 25. Lynch HT, Smyrk T. Hereditary nonpolyposis colorectal cancer (Lynch syndrome). An updated review[J]. Cancer, 1996, 78(6):1149-1167.