Skip to main content
Erschienen in: Virchows Archiv 5/2004

01.11.2004 | Review Article

The utility of immunohistochemical detection of DNA mismatch repair gene proteins

verfasst von: Jinru Shia, Nathan A. Ellis, David S. Klimstra

Erschienen in: Virchows Archiv | Ausgabe 5/2004

Einloggen, um Zugang zu erhalten

Abstract

Since the development of monoclonal antibodies against the MSH2 protein by Leach et al. in 1996, a series of investigations has been undertaken to determine the utility of immunohistochemical detection of DNA mismatch repair (MMR) gene proteins in the identification of hereditary or sporadic colorectal tumors with microsatellite instability. These studies, however, have been performed with different aims and on different patient populations. Interpretation of these immunohistochemical data relies on a thorough understanding of the biological and technical factors that affect the detection of MMR proteins. In this review, we analyze the data from the published research studies, pointing out the various factors affecting immunohistochemical detection of MMR proteins and projecting the utility of immunohistochemistry in different clinical settings.
Literatur
1.
Zurück zum Zitat Aaltonen LA, Peltomaki P, Leach FS, Sistonen P, Pylkkanen L, Mecklin JP, Jarvinen H, Powell SM, Jen J, Hamilton SR et al (1993) Clues to the pathogenesis of familial colorectal cancer. Science 260:812–816PubMed Aaltonen LA, Peltomaki P, Leach FS, Sistonen P, Pylkkanen L, Mecklin JP, Jarvinen H, Powell SM, Jen J, Hamilton SR et al (1993) Clues to the pathogenesis of familial colorectal cancer. Science 260:812–816PubMed
2.
Zurück zum Zitat Aaltonen LA, Salovaara R, Kristo P, Canzian F, Hemminki A, Peltomaki P, Chadwick RB, Kaariainen H, Eskelinen M, Jarvinen H, Mecklin JP, de la Chapelle A (1998) Incidence of hereditary nonpolyposis colorectal cancer and the feasibility of molecular screening for the disease. N Engl J Med 338:1481–1487CrossRefPubMed Aaltonen LA, Salovaara R, Kristo P, Canzian F, Hemminki A, Peltomaki P, Chadwick RB, Kaariainen H, Eskelinen M, Jarvinen H, Mecklin JP, de la Chapelle A (1998) Incidence of hereditary nonpolyposis colorectal cancer and the feasibility of molecular screening for the disease. N Engl J Med 338:1481–1487CrossRefPubMed
3.
Zurück zum Zitat Aarnio M, Sankila R, Pukkala E, Salovaara R, Aaltonen LA, de la Chapelle A, Peltomaki P, Mecklin JP, Jarvinen HJ (1999) Cancer risk in mutation carriers of DNA-mismatch-repair genes. Int J Cancer 81:214–218CrossRefPubMed Aarnio M, Sankila R, Pukkala E, Salovaara R, Aaltonen LA, de la Chapelle A, Peltomaki P, Mecklin JP, Jarvinen HJ (1999) Cancer risk in mutation carriers of DNA-mismatch-repair genes. Int J Cancer 81:214–218CrossRefPubMed
4.
Zurück zum Zitat Acharya S, Wilson T, Gradia S, Kane MF, Guerrette S, Marsischky GT, Kolodner R, Fishel R (1996) hMSH2 forms specific mispair-binding complexes with hMSH3 and hMSH6. Proc Natl Acad Sci U S A 93:13629–13634CrossRefPubMed Acharya S, Wilson T, Gradia S, Kane MF, Guerrette S, Marsischky GT, Kolodner R, Fishel R (1996) hMSH2 forms specific mispair-binding complexes with hMSH3 and hMSH6. Proc Natl Acad Sci U S A 93:13629–13634CrossRefPubMed
5.
Zurück zum Zitat Bapat BV, Madlensky L, Temple LK, Hiruki T, Redston M, Baron DL, Xia L, Marcus VA, Soravia C, Mitri A, Shen W, Gryfe R, Berk T, Chodirker BN, Cohen Z, Gallinger S (1999) Family history characteristics, tumor microsatellite instability and germline MSH2 and MLH1 mutations in hereditary colorectal cancer. Hum Genet 104:167–176CrossRefPubMed Bapat BV, Madlensky L, Temple LK, Hiruki T, Redston M, Baron DL, Xia L, Marcus VA, Soravia C, Mitri A, Shen W, Gryfe R, Berk T, Chodirker BN, Cohen Z, Gallinger S (1999) Family history characteristics, tumor microsatellite instability and germline MSH2 and MLH1 mutations in hereditary colorectal cancer. Hum Genet 104:167–176CrossRefPubMed
6.
Zurück zum Zitat Berends MJ, Wu Y, Sijmons RH, Mensink RG, van der Sluis T, Hordijk-Hos JM, de Vries EG, Hollema H, Karrenbeld A, Buys CH, van der Zee AG, Hofstra RM, Kleibeuker JH (2002) Molecular and clinical characteristics of MSH6 variants: an analysis of 25 index carriers of a germline variant. Am J Hum Genet 70:26–37CrossRefPubMed Berends MJ, Wu Y, Sijmons RH, Mensink RG, van der Sluis T, Hordijk-Hos JM, de Vries EG, Hollema H, Karrenbeld A, Buys CH, van der Zee AG, Hofstra RM, Kleibeuker JH (2002) Molecular and clinical characteristics of MSH6 variants: an analysis of 25 index carriers of a germline variant. Am J Hum Genet 70:26–37CrossRefPubMed
7.
Zurück zum Zitat Boland CR (2000) Molecular genetics of hereditary nonpolyposis colorectal cancer. Ann N Y Acad Sci 910:50–61PubMed Boland CR (2000) Molecular genetics of hereditary nonpolyposis colorectal cancer. Ann N Y Acad Sci 910:50–61PubMed
8.
Zurück zum Zitat Boland CR, Thibodeau SN, Hamilton SR, Sidransky D, Eshleman JR, Burt RW, Meltzer SJ, Rodriguez-Bigas MA, Fodde R, Ranzani GN, Srivastava S (1998) A National Cancer Institute Workshop on Microsatellite Instability for cancer detection and familial predisposition: development of international criteria for the determination of microsatellite instability in colorectal cancer. Cancer Res 58:5248–5257PubMed Boland CR, Thibodeau SN, Hamilton SR, Sidransky D, Eshleman JR, Burt RW, Meltzer SJ, Rodriguez-Bigas MA, Fodde R, Ranzani GN, Srivastava S (1998) A National Cancer Institute Workshop on Microsatellite Instability for cancer detection and familial predisposition: development of international criteria for the determination of microsatellite instability in colorectal cancer. Cancer Res 58:5248–5257PubMed
9.
Zurück zum Zitat Cawkwell L, Gray S, Murgatroyd H, Sutherland F, Haine L, Longfellow M, O’Loughlin S, Cross D, Kronborg O, Fenger C, Mapstone N, Dixon M, Quirke P (1999) Choice of management strategy for colorectal cancer based on a diagnostic immunohistochemical test for defective mismatch repair. Gut 45:409–415PubMed Cawkwell L, Gray S, Murgatroyd H, Sutherland F, Haine L, Longfellow M, O’Loughlin S, Cross D, Kronborg O, Fenger C, Mapstone N, Dixon M, Quirke P (1999) Choice of management strategy for colorectal cancer based on a diagnostic immunohistochemical test for defective mismatch repair. Gut 45:409–415PubMed
10.
Zurück zum Zitat Chapusot C, Martin L, Bouvier AM, Bonithon-Kopp C, Ecarnot-Laubriet A, Rageot D, Ponnelle T, Laurent Puig P, Faivre J, Piard F (2002) Microsatellite instability and intratumoural heterogeneity in 100 right-sided sporadic colon carcinomas. Br J Cancer 87:400–404CrossRefPubMed Chapusot C, Martin L, Bouvier AM, Bonithon-Kopp C, Ecarnot-Laubriet A, Rageot D, Ponnelle T, Laurent Puig P, Faivre J, Piard F (2002) Microsatellite instability and intratumoural heterogeneity in 100 right-sided sporadic colon carcinomas. Br J Cancer 87:400–404CrossRefPubMed
11.
Zurück zum Zitat Chaves P, Cruz C, Lage P, Claro I, Cravo M, Leitao CN, Soares J (2000) Immunohistochemical detection of mismatch repair gene proteins as a useful tool for the identification of colorectal carcinoma with the mutator phenotype. J Pathol 191:355–360CrossRefPubMed Chaves P, Cruz C, Lage P, Claro I, Cravo M, Leitao CN, Soares J (2000) Immunohistochemical detection of mismatch repair gene proteins as a useful tool for the identification of colorectal carcinoma with the mutator phenotype. J Pathol 191:355–360CrossRefPubMed
12.
Zurück zum Zitat Chiaravalli AM, Furlan D, Facco C, Tibiletti MG, Dionigi A, Casati B, Albarello L, Riva C, Capella C (2001) Immunohistochemical pattern of hMSH2/hMLH1 in familial and sporadic colorectal, gastric, endometrial and ovarian carcinomas with instability in microsatellite sequences. Virchows Arch 438:39–48CrossRefPubMed Chiaravalli AM, Furlan D, Facco C, Tibiletti MG, Dionigi A, Casati B, Albarello L, Riva C, Capella C (2001) Immunohistochemical pattern of hMSH2/hMLH1 in familial and sporadic colorectal, gastric, endometrial and ovarian carcinomas with instability in microsatellite sequences. Virchows Arch 438:39–48CrossRefPubMed
13.
Zurück zum Zitat Cunningham JM, Kim CY, Christensen ER, Tester DJ, Parc Y, Burgart LJ, Halling KC, McDonnell SK, Schaid DJ, Walsh Vockley C, Kubly V, Nelson H, Michels VV, Thibodeau SN (2001) The frequency of hereditary defective mismatch repair in a prospective series of unselected colorectal carcinomas. Am J Hum Genet 69:780–790CrossRefPubMed Cunningham JM, Kim CY, Christensen ER, Tester DJ, Parc Y, Burgart LJ, Halling KC, McDonnell SK, Schaid DJ, Walsh Vockley C, Kubly V, Nelson H, Michels VV, Thibodeau SN (2001) The frequency of hereditary defective mismatch repair in a prospective series of unselected colorectal carcinomas. Am J Hum Genet 69:780–790CrossRefPubMed
14.
Zurück zum Zitat Debniak T, Kurzawski G, Gorski B, Kladny J, Domagala W, Lubinski J (2000) Value of pedigree/clinical data, immunohistochemistry and microsatellite instability analyses in reducing the cost of determining hMLH1 and hMSH2 gene mutations in patients with colorectal cancer. Eur J Cancer 36:49–54CrossRefPubMed Debniak T, Kurzawski G, Gorski B, Kladny J, Domagala W, Lubinski J (2000) Value of pedigree/clinical data, immunohistochemistry and microsatellite instability analyses in reducing the cost of determining hMLH1 and hMSH2 gene mutations in patients with colorectal cancer. Eur J Cancer 36:49–54CrossRefPubMed
15.
Zurück zum Zitat Debniak T, Gorski B, Cybulski C, Jakubowska A, Kurzawski G, Kladny J, Lubinski J (2001) Comparison of Alu-PCR, microsatelite instability, and immunohistochemical analyses in finding features characteristic for hereditary nonpolyposis colorectal cancer. J Cancer Res Clin Oncol 127:565–569CrossRefPubMed Debniak T, Gorski B, Cybulski C, Jakubowska A, Kurzawski G, Kladny J, Lubinski J (2001) Comparison of Alu-PCR, microsatelite instability, and immunohistochemical analyses in finding features characteristic for hereditary nonpolyposis colorectal cancer. J Cancer Res Clin Oncol 127:565–569CrossRefPubMed
16.
Zurück zum Zitat Deng G, Peng E, Gum J, Terdiman J, Sleisenger M, Kim YS (2002) Methylation of hMLH1 promoter correlates with the gene silencing with a region-specific manner in colorectal cancer. Br J Cancer 86:574–579CrossRefPubMed Deng G, Peng E, Gum J, Terdiman J, Sleisenger M, Kim YS (2002) Methylation of hMLH1 promoter correlates with the gene silencing with a region-specific manner in colorectal cancer. Br J Cancer 86:574–579CrossRefPubMed
17.
Zurück zum Zitat Dietmaier W, Wallinger S, Bocker T, Kullmann F, Fishel R, Ruschoff J (1997) Diagnostic microsatellite instability: definition and correlation with mismatch repair protein expression. Cancer Res 57:4749–4756PubMed Dietmaier W, Wallinger S, Bocker T, Kullmann F, Fishel R, Ruschoff J (1997) Diagnostic microsatellite instability: definition and correlation with mismatch repair protein expression. Cancer Res 57:4749–4756PubMed
18.
Zurück zum Zitat Dieumegard B, Grandjouan S, Sabourin JC, Le Bihan ML, Lefrere I, Bellefqih, Pignon JP, Rougier P, Lasser P, Benard J, Couturier D, Bressac-de Paillerets B (2000) Extensive molecular screening for hereditary non-polyposis colorectal cancer. Br J Cancer 82:871–880CrossRefPubMed Dieumegard B, Grandjouan S, Sabourin JC, Le Bihan ML, Lefrere I, Bellefqih, Pignon JP, Rougier P, Lasser P, Benard J, Couturier D, Bressac-de Paillerets B (2000) Extensive molecular screening for hereditary non-polyposis colorectal cancer. Br J Cancer 82:871–880CrossRefPubMed
19.
Zurück zum Zitat Elsaleh H, Joseph D, Grieu F, Zeps N, Spry N, Iacopetta B (2000) Association of tumour site and sex with survival benefit from adjuvant chemotherapy in colorectal cancer. Lancet 355:1745–1750CrossRefPubMed Elsaleh H, Joseph D, Grieu F, Zeps N, Spry N, Iacopetta B (2000) Association of tumour site and sex with survival benefit from adjuvant chemotherapy in colorectal cancer. Lancet 355:1745–1750CrossRefPubMed
20.
Zurück zum Zitat Furukawa T, Konishi F, Masubuchi S, Shitoh K, Nagai H, Tsukamoto T (2002) Densely methylated MLH1 promoter correlates with decreased mRNA expression in sporadic colorectal cancers. Genes Chromosomes Cancer 35:1–10CrossRefPubMed Furukawa T, Konishi F, Masubuchi S, Shitoh K, Nagai H, Tsukamoto T (2002) Densely methylated MLH1 promoter correlates with decreased mRNA expression in sporadic colorectal cancers. Genes Chromosomes Cancer 35:1–10CrossRefPubMed
21.
Zurück zum Zitat Furukawa T, Konishi F, Shitoh K, Kojima M, Nagai H, Tsukamoto T (2002) Evaluation of screening strategy for detecting hereditary nonpolyposis colorectal carcinoma. Cancer 94:911–920CrossRefPubMed Furukawa T, Konishi F, Shitoh K, Kojima M, Nagai H, Tsukamoto T (2002) Evaluation of screening strategy for detecting hereditary nonpolyposis colorectal carcinoma. Cancer 94:911–920CrossRefPubMed
22.
Zurück zum Zitat Halvarsson B, Lindblom A, Rambech E, Lagerstedt K, Nilbert M (2004) Microsatellite instability analysis and/or immunostaining for the diagnosis of hereditary nonpolyposis colorectal cancer? Virchows Arch 444:135–141CrossRefPubMed Halvarsson B, Lindblom A, Rambech E, Lagerstedt K, Nilbert M (2004) Microsatellite instability analysis and/or immunostaining for the diagnosis of hereditary nonpolyposis colorectal cancer? Virchows Arch 444:135–141CrossRefPubMed
23.
Zurück zum Zitat Hendriks Y, Franken P, Dierssen JW, De Leeuw W, Wijnen J, Dreef E, Tops C, Breuning M, Brocker-Vriends A, Vasen H, Fodde R, Morreau H (2003) Conventional and tissue microarray immunohistochemical expression analysis of mismatch repair in hereditary colorectal tumors. Am J Pathol 162:469–477PubMed Hendriks Y, Franken P, Dierssen JW, De Leeuw W, Wijnen J, Dreef E, Tops C, Breuning M, Brocker-Vriends A, Vasen H, Fodde R, Morreau H (2003) Conventional and tissue microarray immunohistochemical expression analysis of mismatch repair in hereditary colorectal tumors. Am J Pathol 162:469–477PubMed
24.
Zurück zum Zitat Herman JG, Umar A, Polyak K, Graff JR, Ahuja N, Issa JP, Markowitz S, Willson JK, Hamilton SR, Kinzler KW, Kane MF, Kolodner RD, Vogelstein B, Kunkel TA, Baylin SB (1998) Incidence and functional consequences of hMLH1 promoter hypermethylation in colorectal carcinoma. Proc Natl Acad Sci U S A 95:6870–6875CrossRefPubMed Herman JG, Umar A, Polyak K, Graff JR, Ahuja N, Issa JP, Markowitz S, Willson JK, Hamilton SR, Kinzler KW, Kane MF, Kolodner RD, Vogelstein B, Kunkel TA, Baylin SB (1998) Incidence and functional consequences of hMLH1 promoter hypermethylation in colorectal carcinoma. Proc Natl Acad Sci U S A 95:6870–6875CrossRefPubMed
25.
Zurück zum Zitat Hoedema R, Monroe T, Bos C, Palmer S, Kim D, Marvin M, Luchtefeld M (2003) Genetic testing for hereditary nonpolyposis colorectal cancer. Am Surg 69:387–392PubMed Hoedema R, Monroe T, Bos C, Palmer S, Kim D, Marvin M, Luchtefeld M (2003) Genetic testing for hereditary nonpolyposis colorectal cancer. Am Surg 69:387–392PubMed
26.
Zurück zum Zitat Jansson A, Arbman G, Zhang H, Sun XF (2003) Combined deficiency of hMLH1, hMSH2, hMSH3 and hMSH6 is an independent prognostic factor in colorectal cancer. Int J Oncol 22:41–49PubMed Jansson A, Arbman G, Zhang H, Sun XF (2003) Combined deficiency of hMLH1, hMSH2, hMSH3 and hMSH6 is an independent prognostic factor in colorectal cancer. Int J Oncol 22:41–49PubMed
27.
Zurück zum Zitat Jeong SY, Shin KH, Shin JH, Ku JL, Shin YK, Park SY, Kim WH, Park JG (2003) Microsatellite instability and mutations in DNA mismatch repair genes in sporadic colorectal cancers. Dis Colon Rectum 46:1069–1077PubMed Jeong SY, Shin KH, Shin JH, Ku JL, Shin YK, Park SY, Kim WH, Park JG (2003) Microsatellite instability and mutations in DNA mismatch repair genes in sporadic colorectal cancers. Dis Colon Rectum 46:1069–1077PubMed
28.
Zurück zum Zitat Jourdan F, Sebbagh N, Comperat E, Mourra N, Flahault A, Olschwang S, Duval A, Hamelin R, Flejou JF (2003) Tissue microarray technology: validation in colorectal carcinoma and analysis of p53, hMLH1, and hMSH2 immunohistochemical expression. Virchows Arch 443:115–121CrossRefPubMed Jourdan F, Sebbagh N, Comperat E, Mourra N, Flahault A, Olschwang S, Duval A, Hamelin R, Flejou JF (2003) Tissue microarray technology: validation in colorectal carcinoma and analysis of p53, hMLH1, and hMSH2 immunohistochemical expression. Virchows Arch 443:115–121CrossRefPubMed
29.
Zurück zum Zitat Kane MF, Loda M, Gaida GM, Lipman J, Mishra R, Goldman H, Jessup JM, Kolodner R (1997) Methylation of the hMLH1 promoter correlates with lack of expression of hMLH1 in sporadic colon tumors and mismatch repair-defective human tumor cell lines. Cancer Res 57:808–811PubMed Kane MF, Loda M, Gaida GM, Lipman J, Mishra R, Goldman H, Jessup JM, Kolodner R (1997) Methylation of the hMLH1 promoter correlates with lack of expression of hMLH1 in sporadic colon tumors and mismatch repair-defective human tumor cell lines. Cancer Res 57:808–811PubMed
30.
Zurück zum Zitat Kim H, Piao Z, Kim JW, Choi JS, Kim NK, Lee JM, Park JH (1998) Expression of hMSH2 and hMLH1 in colorectal carcinomas with microsatellite instability. Pathol Res Pract 194:3–9PubMed Kim H, Piao Z, Kim JW, Choi JS, Kim NK, Lee JM, Park JH (1998) Expression of hMSH2 and hMLH1 in colorectal carcinomas with microsatellite instability. Pathol Res Pract 194:3–9PubMed
31.
Zurück zum Zitat Kim HC, Kim CN, Yu CS, Roh SA, Kim JC (2003) Methylation of the hMLH1 and hMSH2 promoter in early-onset sporadic colorectal carcinomas with microsatellite instability. Int J Colorectal Dis 18:196–202PubMed Kim HC, Kim CN, Yu CS, Roh SA, Kim JC (2003) Methylation of the hMLH1 and hMSH2 promoter in early-onset sporadic colorectal carcinomas with microsatellite instability. Int J Colorectal Dis 18:196–202PubMed
32.
Zurück zum Zitat Kolodner RD, Marsischky GT (1999) Eukaryotic DNA mismatch repair. Curr Opin Genet Dev 9:89–96CrossRefPubMed Kolodner RD, Marsischky GT (1999) Eukaryotic DNA mismatch repair. Curr Opin Genet Dev 9:89–96CrossRefPubMed
33.
Zurück zum Zitat Kuismanen SA, Holmberg MT, Salovaara R, de la Chapelle A, Peltomaki P (2000) Genetic and epigenetic modification of MLH1 accounts for a major share of microsatellite-unstable colorectal cancers. Am J Pathol 156:1773–1779PubMed Kuismanen SA, Holmberg MT, Salovaara R, de la Chapelle A, Peltomaki P (2000) Genetic and epigenetic modification of MLH1 accounts for a major share of microsatellite-unstable colorectal cancers. Am J Pathol 156:1773–1779PubMed
34.
Zurück zum Zitat Lamberti C, Kruse R, Ruelfs C, Caspari R, Wang Y, Jungck M, Mathiak M, Malayeri HR, Friedl W, Sauerbruch T, Propping P (1999) Microsatellite instability-a useful diagnostic tool to select patients at high risk for hereditary non-polyposis colorectal cancer: a study in different groups of patients with colorectal cancer. Gut 44:839–843PubMed Lamberti C, Kruse R, Ruelfs C, Caspari R, Wang Y, Jungck M, Mathiak M, Malayeri HR, Friedl W, Sauerbruch T, Propping P (1999) Microsatellite instability-a useful diagnostic tool to select patients at high risk for hereditary non-polyposis colorectal cancer: a study in different groups of patients with colorectal cancer. Gut 44:839–843PubMed
35.
Zurück zum Zitat Lanza G, Gafa R, Maestri I, Santini A, Matteuzzi M, Cavazzini L (2002) Immunohistochemical pattern of MLH1/MSH2 expression is related to clinical and pathological features in colorectal adenocarcinomas with microsatellite instability. Mod Pathol 15:741–749CrossRefPubMed Lanza G, Gafa R, Maestri I, Santini A, Matteuzzi M, Cavazzini L (2002) Immunohistochemical pattern of MLH1/MSH2 expression is related to clinical and pathological features in colorectal adenocarcinomas with microsatellite instability. Mod Pathol 15:741–749CrossRefPubMed
36.
Zurück zum Zitat Leach FS, Nicolaides NC, Papadopoulos N, Liu B, Jen J, Parsons R, Peltomaki P, Sistonen P, Aaltonen LA, Nystrom-Lahti M et al (1993) Mutations of a mutS homolog in hereditary nonpolyposis colorectal cancer. Cell 75:1215–1225CrossRefPubMed Leach FS, Nicolaides NC, Papadopoulos N, Liu B, Jen J, Parsons R, Peltomaki P, Sistonen P, Aaltonen LA, Nystrom-Lahti M et al (1993) Mutations of a mutS homolog in hereditary nonpolyposis colorectal cancer. Cell 75:1215–1225CrossRefPubMed
37.
Zurück zum Zitat Lindor NM, Burgart LJ, Leontovich O, Goldberg RM, Cunningham JM, Sargent DJ, Walsh-Vockley C, Petersen GM, Walsh MD, Leggett BA, Young JP, Barker MA, Jass JR, Hopper J, Gallinger S, Bapat B, Redston M, Thibodeau SN (2002) Immunohistochemistry versus microsatellite instability testing in phenotyping colorectal tumors. J Clin Oncol 20:1043–1048CrossRefPubMed Lindor NM, Burgart LJ, Leontovich O, Goldberg RM, Cunningham JM, Sargent DJ, Walsh-Vockley C, Petersen GM, Walsh MD, Leggett BA, Young JP, Barker MA, Jass JR, Hopper J, Gallinger S, Bapat B, Redston M, Thibodeau SN (2002) Immunohistochemistry versus microsatellite instability testing in phenotyping colorectal tumors. J Clin Oncol 20:1043–1048CrossRefPubMed
38.
Zurück zum Zitat Liu B, Parsons R, Papadopoulos N, Nicolaides NC, Lynch HT, Watson P, Jass JR, Dunlop M, Wyllie A, Peltomaki P, de la Chapelle A, Hamilton SR, Vogelstein B, Kinzler KW (1996) Analysis of mismatch repair genes in hereditary non-polyposis colorectal cancer patients. Nat Med 2:169–174CrossRefPubMed Liu B, Parsons R, Papadopoulos N, Nicolaides NC, Lynch HT, Watson P, Jass JR, Dunlop M, Wyllie A, Peltomaki P, de la Chapelle A, Hamilton SR, Vogelstein B, Kinzler KW (1996) Analysis of mismatch repair genes in hereditary non-polyposis colorectal cancer patients. Nat Med 2:169–174CrossRefPubMed
39.
Zurück zum Zitat Liu T, Tannergard P, Hackman P, Rubio C, Kressner U, Lindmark G, Hellgren D, Lambert B, Lindblom A (1999) Missense mutations in hMLH1 associated with colorectal cancer. Hum Genet 105:437–441CrossRefPubMed Liu T, Tannergard P, Hackman P, Rubio C, Kressner U, Lindmark G, Hellgren D, Lambert B, Lindblom A (1999) Missense mutations in hMLH1 associated with colorectal cancer. Hum Genet 105:437–441CrossRefPubMed
40.
Zurück zum Zitat Liu T, Wahlberg S, Burek E, Lindblom P, Rubio C, Lindblom A (2000) Microsatellite instability as a predictor of a mutation in a DNA mismatch repair gene in familial colorectal cancer. Genes Chromosomes Cancer 27:17–25CrossRefPubMed Liu T, Wahlberg S, Burek E, Lindblom P, Rubio C, Lindblom A (2000) Microsatellite instability as a predictor of a mutation in a DNA mismatch repair gene in familial colorectal cancer. Genes Chromosomes Cancer 27:17–25CrossRefPubMed
41.
Zurück zum Zitat Marcus VA, Madlensky L, Gryfe R, Kim H, So K, Millar A, Temple LK, Hsieh E, Hiruki T, Narod S, Bapat BV, Gallinger S, Redston M (1999) Immunohistochemistry for hMLH1 and hMSH2: a practical test for DNA mismatch repair-deficient tumors. Am J Surg Pathol 23:1248–1255CrossRefPubMed Marcus VA, Madlensky L, Gryfe R, Kim H, So K, Millar A, Temple LK, Hsieh E, Hiruki T, Narod S, Bapat BV, Gallinger S, Redston M (1999) Immunohistochemistry for hMLH1 and hMSH2: a practical test for DNA mismatch repair-deficient tumors. Am J Surg Pathol 23:1248–1255CrossRefPubMed
42.
Zurück zum Zitat Miyakura Y, Sugano K, Konishi F, Ichikawa A, Maekawa M, Shitoh K, Igarashi S, Kotake K, Koyama Y, Nagai H (2001) Extensive methylation of hMLH1 promoter region predominates in proximal colon cancer with microsatellite instability. Gastroenterology 121:1300–1309PubMed Miyakura Y, Sugano K, Konishi F, Ichikawa A, Maekawa M, Shitoh K, Igarashi S, Kotake K, Koyama Y, Nagai H (2001) Extensive methylation of hMLH1 promoter region predominates in proximal colon cancer with microsatellite instability. Gastroenterology 121:1300–1309PubMed
43.
Zurück zum Zitat Modrich P (1991) Mechanisms and biological effects of mismatch repair. Annu Rev Genet 25:229–253CrossRefPubMed Modrich P (1991) Mechanisms and biological effects of mismatch repair. Annu Rev Genet 25:229–253CrossRefPubMed
44.
Zurück zum Zitat Muller W, Burgart LJ, Krause-Paulus R, Thibodeau SN, Almeida M, Edmonston TB, Boland CR, Sutter C, Jass JR, Lindblom A, Lubinski J, MacDermot K, Sanders DS, Morreau H, Muller A, Oliani C, Orntoft T, Ponz De Leon M, Rosty C, Rodriguez-Bigas M, Ruschoff J, Ruszkiewicz A, Sabourin J, Salovaara R, Moslein G (2001) The reliability of immunohistochemistry as a prescreening method for the diagnosis of hereditary nonpolyposis colorectal cancer (HNPCC)—results of an international collaborative study. Fam Cancer 1:87–92CrossRefPubMed Muller W, Burgart LJ, Krause-Paulus R, Thibodeau SN, Almeida M, Edmonston TB, Boland CR, Sutter C, Jass JR, Lindblom A, Lubinski J, MacDermot K, Sanders DS, Morreau H, Muller A, Oliani C, Orntoft T, Ponz De Leon M, Rosty C, Rodriguez-Bigas M, Ruschoff J, Ruszkiewicz A, Sabourin J, Salovaara R, Moslein G (2001) The reliability of immunohistochemistry as a prescreening method for the diagnosis of hereditary nonpolyposis colorectal cancer (HNPCC)—results of an international collaborative study. Fam Cancer 1:87–92CrossRefPubMed
45.
Zurück zum Zitat Peltomaki P (2003) Role of DNA mismatch repair defects in the pathogenesis of human cancer. J Clin Oncol 21:1174–1179CrossRefPubMed Peltomaki P (2003) Role of DNA mismatch repair defects in the pathogenesis of human cancer. J Clin Oncol 21:1174–1179CrossRefPubMed
46.
Zurück zum Zitat Peltomaki P, Vasen HF (1997) Mutations predisposing to hereditary nonpolyposis colorectal cancer: database and results of a collaborative study. The International Collaborative Group on Hereditary Nonpolyposis Colorectal Cancer. Gastroenterology 113:1146–1158PubMed Peltomaki P, Vasen HF (1997) Mutations predisposing to hereditary nonpolyposis colorectal cancer: database and results of a collaborative study. The International Collaborative Group on Hereditary Nonpolyposis Colorectal Cancer. Gastroenterology 113:1146–1158PubMed
47.
Zurück zum Zitat Potocnik U, Glavac D, Golouh R, Ravnik-Glavac M (2001) Causes of microsatellite instability in colorectal tumors: implications for hereditary non-polyposis colorectal cancer screening. Cancer Genet Cytogenet 126:85–96CrossRefPubMed Potocnik U, Glavac D, Golouh R, Ravnik-Glavac M (2001) Causes of microsatellite instability in colorectal tumors: implications for hereditary non-polyposis colorectal cancer screening. Cancer Genet Cytogenet 126:85–96CrossRefPubMed
48.
Zurück zum Zitat Ribic CM, Sargent DJ, Moore MJ, Thibodeau SN, French AJ, Goldberg RM, Hamilton SR, Laurent-Puig P, Gryfe R, Shepherd LE, Tu D, Redston M, Gallinger S (2003) Tumor microsatellite-instability status as a predictor of benefit from fluorouracil-based adjuvant chemotherapy for colon cancer. N Engl J Med 349:247–257CrossRefPubMed Ribic CM, Sargent DJ, Moore MJ, Thibodeau SN, French AJ, Goldberg RM, Hamilton SR, Laurent-Puig P, Gryfe R, Shepherd LE, Tu D, Redston M, Gallinger S (2003) Tumor microsatellite-instability status as a predictor of benefit from fluorouracil-based adjuvant chemotherapy for colon cancer. N Engl J Med 349:247–257CrossRefPubMed
49.
Zurück zum Zitat Rigau V, Sebbagh N, Olschwang S, Paraf F, Mourra N, Parc Y, Flejou JF (2003) Microsatellite instability in colorectal carcinoma. The comparison of immunohistochemistry and molecular biology suggests a role for hMSH6 [correction of hMLH6] immunostaining. Arch Pathol Lab Med 127:694–700PubMed Rigau V, Sebbagh N, Olschwang S, Paraf F, Mourra N, Parc Y, Flejou JF (2003) Microsatellite instability in colorectal carcinoma. The comparison of immunohistochemistry and molecular biology suggests a role for hMSH6 [correction of hMLH6] immunostaining. Arch Pathol Lab Med 127:694–700PubMed
50.
Zurück zum Zitat Ruszkiewicz A, Bennett G, Moore J, Manavis J, Rudzki B, Shen L, Suthers G (2002) Correlation of mismatch repair genes immunohistochemistry and microsatellite instability status in HNPCC-associated tumours. Pathology 34:541–547PubMed Ruszkiewicz A, Bennett G, Moore J, Manavis J, Rudzki B, Shen L, Suthers G (2002) Correlation of mismatch repair genes immunohistochemistry and microsatellite instability status in HNPCC-associated tumours. Pathology 34:541–547PubMed
51.
Zurück zum Zitat Salahshor S, Koelble K, Rubio C, Lindblom A (2001) Microsatellite Instability and hMLH1 and hMSH2 expression analysis in familial and sporadic colorectal cancer. Lab Invest 81:535–541PubMed Salahshor S, Koelble K, Rubio C, Lindblom A (2001) Microsatellite Instability and hMLH1 and hMSH2 expression analysis in familial and sporadic colorectal cancer. Lab Invest 81:535–541PubMed
52.
Zurück zum Zitat Scartozzi M, Bianchi F, Rosati S, Galizia E, Antolini A, Loretelli C, Piga A, Bearzi I, Cellerino R, Porfiri E (2002) 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 Clin Oncol 20:1203–1208CrossRefPubMed Scartozzi M, Bianchi F, Rosati S, Galizia E, Antolini A, Loretelli C, Piga A, Bearzi I, Cellerino R, Porfiri E (2002) 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 Clin Oncol 20:1203–1208CrossRefPubMed
53.
Zurück zum Zitat Shia J, Ellis NA, Paty PB, Nash GM, Qin J, Offit K, Zhang XM, Markowitz AJ, Nafa K, Guillem JG, Wong WD, Gerald WL, Klimstra DS (2003) Value of histopathology in predicting microsatellite instability in hereditary nonpolyposis colorectal cancer and sporadic colorectal cancer. Am J Surg Pathol 27:1407–1417PubMed Shia J, Ellis NA, Paty PB, Nash GM, Qin J, Offit K, Zhang XM, Markowitz AJ, Nafa K, Guillem JG, Wong WD, Gerald WL, Klimstra DS (2003) Value of histopathology in predicting microsatellite instability in hereditary nonpolyposis colorectal cancer and sporadic colorectal cancer. Am J Surg Pathol 27:1407–1417PubMed
54.
Zurück zum Zitat Stone JG, Robertson D, Houlston RS (2001) Immunohistochemistry for MSH2 and MHL1: a method for identifying mismatch repair deficient colorectal cancer. J Clin Pathol 54:484–487CrossRefPubMed Stone JG, Robertson D, Houlston RS (2001) Immunohistochemistry for MSH2 and MHL1: a method for identifying mismatch repair deficient colorectal cancer. J Clin Pathol 54:484–487CrossRefPubMed
55.
Zurück zum Zitat Terdiman JP, Gum JR Jr, Conrad PG, Miller GA, Weinberg V, Crawley SC, Levin TR, Reeves C, Schmitt A, Hepburn M, Sleisenger MH, Kim YS (2001) Efficient detection of hereditary nonpolyposis colorectal cancer gene carriers by screening for tumor microsatellite instability before germline genetic testing. Gastroenterology 120:21–30PubMed Terdiman JP, Gum JR Jr, Conrad PG, Miller GA, Weinberg V, Crawley SC, Levin TR, Reeves C, Schmitt A, Hepburn M, Sleisenger MH, Kim YS (2001) Efficient detection of hereditary nonpolyposis colorectal cancer gene carriers by screening for tumor microsatellite instability before germline genetic testing. Gastroenterology 120:21–30PubMed
56.
Zurück zum Zitat Thibodeau SN, French AJ, Cunningham JM, Tester D, Burgart LJ, Roche PC, McDonnell SK, Schaid DJ, Vockley CW, Michels VV, Farr GH Jr, O’Connell MJ (1998) Microsatellite instability in colorectal cancer: different mutator phenotypes and the principal involvement of hMLH1. Cancer Res 58:1713–1718PubMed Thibodeau SN, French AJ, Cunningham JM, Tester D, Burgart LJ, Roche PC, McDonnell SK, Schaid DJ, Vockley CW, Michels VV, Farr GH Jr, O’Connell MJ (1998) Microsatellite instability in colorectal cancer: different mutator phenotypes and the principal involvement of hMLH1. Cancer Res 58:1713–1718PubMed
57.
Zurück zum Zitat Umar A, Boland CR, Terdiman JP, Syngal S, de la Chapelle A, Ruschoff J, Fishel R, Lindor NM, Burgart LJ, Hamelin R, Hamilton SR, Hiatt RA, Jass J, Lindblom A, Lynch HT, Peltomaki P, Ramsey SD, Rodriguez-Bigas MA, Vasen HF, Hawk ET, Barrett JC, Freedman AN, Srivastava S (2004) Revised Bethesda Guidelines for hereditary nonpolyposis colorectal cancer (Lynch syndrome) and microsatellite instability. J Natl Cancer Inst 96:261–268CrossRefPubMed Umar A, Boland CR, Terdiman JP, Syngal S, de la Chapelle A, Ruschoff J, Fishel R, Lindor NM, Burgart LJ, Hamelin R, Hamilton SR, Hiatt RA, Jass J, Lindblom A, Lynch HT, Peltomaki P, Ramsey SD, Rodriguez-Bigas MA, Vasen HF, Hawk ET, Barrett JC, Freedman AN, Srivastava S (2004) Revised Bethesda Guidelines for hereditary nonpolyposis colorectal cancer (Lynch syndrome) and microsatellite instability. J Natl Cancer Inst 96:261–268CrossRefPubMed
58.
Zurück zum Zitat Van Rijnsoever M, Elsaleh H, Joseph D, McCaul K, Iacopetta B (2003) CpG island methylator phenotype is an independent predictor of survival benefit from 5-fluorouracil in stage III colorectal cancer. Clin Cancer Res 9:2898–2903PubMed Van Rijnsoever M, Elsaleh H, Joseph D, McCaul K, Iacopetta B (2003) CpG island methylator phenotype is an independent predictor of survival benefit from 5-fluorouracil in stage III colorectal cancer. Clin Cancer Res 9:2898–2903PubMed
59.
Zurück zum Zitat Vasen HF, Wijnen JT, Menko FH, Kleibeuker JH, Taal BG, Griffioen G, Nagengast FM, Meijers-Heijboer EH, Bertario L, Varesco L, Bisgaard ML, Mohr J, Fodde R, Khan PM (1996) Cancer risk in families with hereditary nonpolyposis colorectal cancer diagnosed by mutation analysis. Gastroenterology 110:1020–1027PubMed Vasen HF, Wijnen JT, Menko FH, Kleibeuker JH, Taal BG, Griffioen G, Nagengast FM, Meijers-Heijboer EH, Bertario L, Varesco L, Bisgaard ML, Mohr J, Fodde R, Khan PM (1996) Cancer risk in families with hereditary nonpolyposis colorectal cancer diagnosed by mutation analysis. Gastroenterology 110:1020–1027PubMed
60.
Zurück zum Zitat Wagner A, Barrows A, Wijnen JT, van der Klift H, Franken PF, Verkuijlen P, Nakagawa H, Geugien M, Jaghmohan-Changur S, Breukel C, Meijers-Heijboer H, Morreau H, van Puijenbroek M, Burn J, Coronel S, Kinarski Y, Okimoto R, Watson P, Lynch JF, de la Chapelle A, Lynch HT, Fodde R (2003) Molecular analysis of hereditary nonpolyposis colorectal cancer in the United States: high mutation detection rate among clinically selected families and characterization of an American founder genomic deletion of the MSH2 gene. Am J Hum Genet 72:1088–1100CrossRefPubMed Wagner A, Barrows A, Wijnen JT, van der Klift H, Franken PF, Verkuijlen P, Nakagawa H, Geugien M, Jaghmohan-Changur S, Breukel C, Meijers-Heijboer H, Morreau H, van Puijenbroek M, Burn J, Coronel S, Kinarski Y, Okimoto R, Watson P, Lynch JF, de la Chapelle A, Lynch HT, Fodde R (2003) Molecular analysis of hereditary nonpolyposis colorectal cancer in the United States: high mutation detection rate among clinically selected families and characterization of an American founder genomic deletion of the MSH2 gene. Am J Hum Genet 72:1088–1100CrossRefPubMed
61.
Zurück zum Zitat Wahlberg SS, Schmeits J, Thomas G, Loda M, Garber J, Syngal S, Kolodner RD, Fox E (2002) Evaluation of microsatellite instability and immunohistochemistry for the prediction of germ-line MSH2 and MLH1 mutations in hereditary nonpolyposis colon cancer families. Cancer Res 62:3485–3492PubMed Wahlberg SS, Schmeits J, Thomas G, Loda M, Garber J, Syngal S, Kolodner RD, Fox E (2002) Evaluation of microsatellite instability and immunohistochemistry for the prediction of germ-line MSH2 and MLH1 mutations in hereditary nonpolyposis colon cancer families. Cancer Res 62:3485–3492PubMed
62.
Zurück zum Zitat Ward R, Meagher A, Tomlinson I, O’Connor T, Norrie M, Wu R, Hawkins N (2001) Microsatellite instability and the clinicopathological features of sporadic colorectal cancer. Gut 48:821–829CrossRefPubMed Ward R, Meagher A, Tomlinson I, O’Connor T, Norrie M, Wu R, Hawkins N (2001) Microsatellite instability and the clinicopathological features of sporadic colorectal cancer. Gut 48:821–829CrossRefPubMed
63.
Zurück zum Zitat Wheeler JM, Loukola A, Aaltonen LA, Mortensen NJ, Bodmer WF (2000) The role of hypermethylation of the hMLH1 promoter region in HNPCC versus MSI+ sporadic colorectal cancers. J Med Genet 37:588–592CrossRefPubMed Wheeler JM, Loukola A, Aaltonen LA, Mortensen NJ, Bodmer WF (2000) The role of hypermethylation of the hMLH1 promoter region in HNPCC versus MSI+ sporadic colorectal cancers. J Med Genet 37:588–592CrossRefPubMed
64.
Zurück zum Zitat Yan H, Papadopoulos N, Marra G, Perrera C, Jiricny J, Boland CR, Lynch HT, Chadwick RB, de la Chapelle A, Berg K, Eshleman JR, Yuan W, Markowitz S, Laken SJ, Lengauer C, Kinzler KW, Vogelstein B (2000) Conversion of diploidy to haploidy. Nature 403:723–724CrossRefPubMed Yan H, Papadopoulos N, Marra G, Perrera C, Jiricny J, Boland CR, Lynch HT, Chadwick RB, de la Chapelle A, Berg K, Eshleman JR, Yuan W, Markowitz S, Laken SJ, Lengauer C, Kinzler KW, Vogelstein B (2000) Conversion of diploidy to haploidy. Nature 403:723–724CrossRefPubMed
65.
Zurück zum Zitat Young J, Simms LA, Biden KG, Wynter C, Whitehall V, Karamatic R, George J, Goldblatt J, Walpole I, Robin SA, Borten MM, Stitz R, Searle J, McKeone D, Fraser L, Purdie DR, Podger K, Price R, Buttenshaw R, Walsh MD, Barker M, Leggett BA, Jass JR (2001) Features of colorectal cancers with high-level microsatellite instability occurring in familial and sporadic settings: parallel pathways of tumorigenesis. Am J Pathol 159:2107–2116PubMed Young J, Simms LA, Biden KG, Wynter C, Whitehall V, Karamatic R, George J, Goldblatt J, Walpole I, Robin SA, Borten MM, Stitz R, Searle J, McKeone D, Fraser L, Purdie DR, Podger K, Price R, Buttenshaw R, Walsh MD, Barker M, Leggett BA, Jass JR (2001) Features of colorectal cancers with high-level microsatellite instability occurring in familial and sporadic settings: parallel pathways of tumorigenesis. Am J Pathol 159:2107–2116PubMed
Metadaten
Titel
The utility of immunohistochemical detection of DNA mismatch repair gene proteins
verfasst von
Jinru Shia
Nathan A. Ellis
David S. Klimstra
Publikationsdatum
01.11.2004
Verlag
Springer-Verlag
Erschienen in
Virchows Archiv / Ausgabe 5/2004
Print ISSN: 0945-6317
Elektronische ISSN: 1432-2307
DOI
https://doi.org/10.1007/s00428-004-1090-5

Weitere Artikel der Ausgabe 5/2004

Virchows Archiv 5/2004 Zur Ausgabe

Neu im Fachgebiet Pathologie