Abstract
It is now generally recognized that a specific subset of those patients clinically defined as having hereditary non polyposis colon cancer (HNPCC) have germline mutations in any one of several genes involved in DNA mismatch repair (MMR). This important subset of HNPCC families is now defined as having Lynch syndrome. A considerable amount of data has shown that tumors from patients with Lynch syndrome have characteristic features resulting from the underlying molecular involvement of defective MMR, that is, the presence of microsatellite instability (MSI) and the absence of MMR protein expression by immunohistochemistry (IHC). As a result, identifying patients with Lynch syndrome can now be accomplished by testing tumors for these tumor-related changes. Together, MSI and IHC are powerful tools that help identify individuals at risk for having Lynch syndrome and to distinguish these cases from HNPCC cases with other hereditary gene defects. Furthermore, IHC analysis provides valuable clues as to which MMR gene is mutated, allowing for comprehensive mutational analyses of that gene. Here, we discuss the current and historical perspectives regarding MSI and IHC analyses in tumors from sporadic colon cancer and from patients with Lynch syndrome. Given this background, we also provide a testing strategy for the identification of patients at risk for Lynch syndrome and subsequent gene testing.
Similar content being viewed by others
References
Y Ionov MA Peinado S. Malkhosyan et al. (1993) ArticleTitleUbiquitous somatic mutations in simple repeated sequences reveal a new mechanism for colonic carcinogenesis Nature 363 IssueID6429 558–61 Occurrence Handle10.1038/363558a0 Occurrence Handle8505985
SN Thibodeau G Bren D. Schaid (1993) ArticleTitleMicrosatellite instability in cancer of the proximal colon Science 260 IssueID5109 816–9 Occurrence Handle8484122
LA Aaltonen P Peltomaki FS. Leach et al. (1993) ArticleTitleClues to the pathogenesis of familial colorectal cancer Science 260 IssueID5109 812–6 Occurrence Handle8484121
P Peltomaki LA Aaltonen P. Sistonen et al. (1993) ArticleTitleGenetic mapping of a locus predisposing to human colorectal cancer Science 260 IssueID5109 810–12 Occurrence Handle8484120
CR Boland SN Thibodeau SR Hamilton et al. (1998) ArticleTitleA 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 IssueID22 5248–57 Occurrence Handle9823339
M Strand TA Prolla RM Liskay TD. Petes (1993) ArticleTitleDestabilization of tracts of simple repetitive DNA in yeast by mutations affecting DNA mismatch repair Nature 365 IssueID6443 274–6 Occurrence Handle10.1038/365274a0 Occurrence Handle8371783
R Fishel MK Lescoe MR Rao et al. (1993) ArticleTitleThe human mutator gene homolog MSH2 and its association with hereditary nonpolyposis colon cancer Cell 75 IssueID5 1027–38 Occurrence Handle10.1016/0092-8674(93)90546-3 Occurrence Handle8252616
FS Leach NC Nicolaides N Papadopoulos et al. (1993) ArticleTitleMutations of a mutS homolog in hereditary nonpolyposis colorectal cancer Cell 75 IssueID6 1215–25 Occurrence Handle10.1016/0092-8674(93)90330-S Occurrence Handle8261515
DC Chung AK. Rustgi (2003) ArticleTitleThe hereditary nonpolyposis colorectal cancer syndrome: Genetics and clinical implications Ann Intern Med 138 IssueID7 560–70 Occurrence Handle12667026
R Fishel RD. Kolodner (1995) ArticleTitleIdentification of mismatch repair genes and their role in the development of cancer Curr Opin Genet Dev 5 IssueID3 382–95 Occurrence Handle10.1016/0959-437X(95)80055-7 Occurrence Handle7549435
RA Lothe P Peltomaki GI Meling et al. (1993) ArticleTitleGenomic instability in colorectal cancer: Relationship to clinicopathological variables and family history Cancer Res 53 IssueID24 5849–52 Occurrence Handle8261392
U Patel HC Chen S. Banerjee (1994) ArticleTitleDinucleotide repeat polymorphisms at nine loci in sporadic colorectal cancer Cell Mol Biol Res 40 IssueID7–8 683–91 Occurrence Handle7787886
RF Jacoby DJ Marshall S Kailas et al. (1995) ArticleTitleGenetic instability associated with adenoma to carcinoma progression in hereditary nonpolyposis colon cancer Gastroenterology 109 IssueID1 73–82 Occurrence Handle10.1016/0016-5085(95)90270-8 Occurrence Handle7797042
G Ishimaru J Adachi M Shiseki et al. (1995) ArticleTitleJ. Microsatellite instability in primary and metastatic colorectal cancers Int J Cancer 64 IssueID3 153–17 Occurrence Handle7622302
SN Thibodeau AJ French JM Cunningham et al. (1998) ArticleTitleMicrosatellite instability in colorectal cancer: Different mutator phenotypes and the principal involvement of hMLH1 Cancer Res 58 IssueID8 1713–8 Occurrence Handle9563488
W Dietmaier S Wallinger T Bocker et al. (1997) ArticleTitleDiagnostic microsatellite instability: Definition and correlation with mismatch repair protein expression Cancer Res 57 IssueID21 4749–56 Occurrence Handle9354436
T Bocker J Diermann W. Friedl et al. (1997) ArticleTitleMicrosatellite instability analysis: A multicenter study for reliability and quality control Cancer Res 57 IssueID21 4739–43 Occurrence Handle9354434
JM Hoang PH Cottu B Thuille et al. (1997) ArticleTitleBAT-26, an indicator of the replication error phenotype in colorectal cancers and cell lines Cancer Res 57 IssueID2 300–3 Occurrence Handle9000572
R Gryfe H Kim ET Hsieh et al. (2000) ArticleTitleTumor microsatellite instability and clinical outcome in young patients with colorectal cancer N Engl J Med 342 IssueID2 69–77 Occurrence Handle10.1056/NEJM200001133420201 Occurrence Handle10631274
P Laiho V Launonen P Lahermo et al. (2002) ArticleTitleLow-level microsatellite instability in most colorectal carcinomas Cancer Res 62 IssueID4 1166–70 Occurrence Handle11861399
U Potocnik D Glavac R Golouh M. Ravnik-Glavac (2001) ArticleTitleCauses of microsatellite instability in colorectal tumors: Implications for hereditary non-polyposis colorectal cancer screening Cancer Genet Cytogenet 126 IssueID2 85–96 Occurrence Handle10.1016/S0165-4608(00)00399-X Occurrence Handle11376800
KC Halling AJ French SK McDonnell et al. (1999) ArticleTitleMicrosatellite instability and 8p allelic imbalance in stage B2 and C colorectal cancers J Natl Cancer Inst 91 IssueID15 1295–303 Occurrence Handle10.1093/jnci/91.15.1295 Occurrence Handle10433618
R Sankila LA Aaltonen HJ Jarvinen JP. Mecklin (1996) ArticleTitleBetter survival rates in patients with MLH1-associated hereditary colorectal cancer Gastroenterology 110 IssueID3 682–7 Occurrence Handle10.1053/gast.1996.v110.pm8608876 Occurrence Handle8608876
H Kim J Jen B Vogelstein SR. Hamilton (1994) ArticleTitleClinical and pathological characteristics of sporadic colorectal carcinomas with DNA replication errors in microsatellite sequences Am J Pathol 145 IssueID1 148–56 Occurrence Handle8030745
JR Jass KA Do LA Simms et al. (1998) ArticleTitleMorphology of sporadic colorectal cancer with DNA replication errors Gut 42 IssueID5 673–9 Occurrence Handle9659163
M Risio G Reato PF Celle Particledi et al. (1996) ArticleTitleMicrosatellite instability is associated with the histological features of the tumor in nonfamilial colorectal cancer Cancer Res 56 IssueID23 5470–4 Occurrence Handle8968103
I Tomlinson S Halford L Aaltonen et al. (2002) ArticleTitleDoes MSI-low exist? J Pathol 197 IssueID1 6–13 Occurrence Handle10.1002/path.1071 Occurrence Handle12081205
M Konishi R Kikuchi-Yanoshita K Tanaka et al. (1996) ArticleTitleMolecular nature of colon tumors in hereditary nonpolyposis colon cancer, familial polyposis, and sporadic colon cancer Gastroenterology 111 IssueID2 307–17 Occurrence Handle10.1053/gast.1996.v111.pm8690195 Occurrence Handle8690195
JR Jass KG Biden MC Cummings et al. (1999) ArticleTitleCharacterisation of a subtype of colorectal cancer combining features of the suppressor and mild mutator pathways J Clin Pathol 52 IssueID6 455–60 Occurrence Handle10562815
JM Cunningham CY Kim ER Christensen et al. (2001) ArticleTitleThe frequency of hereditary defective mismatch repair in a prospective series of unselected colorectal carcinomas Am J Hum Genet 69 IssueID4 780–90 Occurrence Handle10.1086/323658 Occurrence Handle11524701
NM Lindor LJ Burgart O Leontovich et al. (2002) ArticleTitleImmunohistochemistry versus microsatellite instability testing in phenotyping colorectal tumors J Clin Oncol 20 IssueID4 1043–8 Occurrence Handle10.1200/JCO.20.4.1043 Occurrence Handle11844828
JP Terdiman JR Gum SuffixJr. PG Conrad et al. (2001) ArticleTitleEfficient detection of hereditary nonpolyposis colorectal cancer gene carriers by screening for tumor microsatellite instability before germline genetic testing Gastroenterology 120 IssueID1 21–30 Occurrence Handle10.1053/gast.2001.20874 Occurrence Handle11208710
A Ruszkiewicz G Bennett J Moore et al. (2002) ArticleTitleCorrelation of mismatch repair genes immunohistochemistry and microsatellite instability status in HNPCC-associated tumours Pathology 34 IssueID6 541–7 Occurrence Handle12555992
B Halvarsson A Lindblom E Rambech et al. (2004) ArticleTitleMicrosatellite instability analysis and/or immunostaining for the diagnosis of hereditary nonpolyposis colorectal cancer? Virch Arch 444 IssueID2 135–41 Occurrence Handle10.1007/s00428-003-0922-z
A Loukola K Eklin P Laiho et al. (2001) ArticleTitleMicrosatellite marker analysis in screening for hereditary nonpolyposis colorectal cancer Cancer Res 61 IssueID11 4545–9 Occurrence Handle11389088
WM Brueckl C Moesch T Brabletz et al. (2003) ArticleTitleRelationship between microsatellite instability, response and survival in palliative patients with colorectal cancer undergoing first-line chemotherapy Anticancer Res 23 IssueID2C 1773–7 Occurrence Handle12820457
M Colombino A Cossu A Arba et al. (2003) ArticleTitleMicrosatellite instability and mutation analysis among southern Italian patients with colorectal carcinoma: Detection of different alterations accounting for MLH1 and MSH2 inactivation in familial cases Ann Oncol 14 IssueID10 1530–6 Occurrence Handle10.1093/annonc/mdg402 Occurrence Handle14504054
G Lanza R Gafa I. Maestri et al. (2002) ArticleTitleImmunohistochemical pattern of MLH1/MSH2 expression is related to clinical and pathological features in colorectal adenocarcinomas with microsatellite instability Mod Pathol 15 IssueID7 741–9 Occurrence Handle10.1097/01.MP.0000018979.68686.B2 Occurrence Handle12118112
AE Jong Particlede M Puijenbroek Particlevan Y Hendriks et al. (2004) ArticleTitleMicrosatellite instability, immunohistochemistry, and additional PMS2 staining in suspected hereditary nonpolyposis colorectal cancer Clin Cancer Res 10 IssueID3 972–80 Occurrence Handle14871975
JG Stone D Robertson RS. Houlston (2001) ArticleTitleImmunohistochemistry for MSH2 and MHL1: A method for identifying mismatch repair deficient colorectal cancer J Clin Pathol 54 IssueID6 484–7 Occurrence Handle10.1136/jcp.54.6.484 Occurrence Handle11376026
V Rigau N Sebbagh S Olschwang et al. (2003) ArticleTitleMicrosatellite instability in colorectal carcinoma. The comparison of immunohistochemistry and molecular biology suggests a role for [correction of hMLH6] hMSH6 immunostaining Arch Pathol Lab Med 127 IssueID6 694–700 Occurrence Handle12741892
L Verma MF Kane C Brassett et al. (1999) ArticleTitleMononucleotide microsatellite instability and germline MSH6 mutation analysis in early onset colorectal cancer J Med Genet 36 IssueID9 678–82 Occurrence Handle10507723
J Plaschke C Kruppa R Tischler et al. (2000) ArticleTitleSequence analysis of the mismatch repair gene hMSH6 in the germline of patients with familial and sporadic colorectal cancer Int J Cancer 85 IssueID5 606–13 Occurrence Handle10.1002/(SICI)1097-0215(20000301)85:5<606::AID-IJC2>3.0.CO;2-B Occurrence Handle10699937
N Papadopoulos NC Nicolaides B Liu et al. (1995) ArticleTitleMutations of GTBP in genetically unstable cells Science 268 IssueID5219 1915–7 Occurrence Handle7604266
NP Bhattacharyya A Skandalis et al. (1994) ArticleTitleMutator phenotypes in human colorectal carcinoma cell lines Proc Natl Acad Sci USA 91 IssueID14 6319–23 Occurrence Handle8022779
JM Cunningham ER Christensen DJ Tester et al. (1998) ArticleTitleHypermethylation of the hMLH1 promoter in colon cancer with microsatellite instability Cancer Res 58 IssueID15 3455–60 Occurrence Handle9699680
MF Kane M Loda GM Gaida et al. (1997) ArticleTitleMethylation 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 IssueID5 808–11 Occurrence Handle9041175
A Umar JI Risinger ET Hawk JC. Barrett (2004) ArticleTitleTesting guidelines for hereditary non-polyposis colorectal cancer Nat Rev Cancer 4 IssueID2 153–8 Occurrence Handle14964310
HP Wullenweber C Sutter F Autschbach et al. (2001) ArticleTitleEvaluation of Bethesda guidelines in relation to microsatellite instability Dis Colon Rectum 44 IssueID9 1281–9 Occurrence Handle11584201
S Syngal EA Fox C Eng et al. (2000) ArticleTitleSensitivity and specificity of clinical criteria for hereditary non-polyposis colorectal cancer associated mutations in MSH2 and MLH1 J Med Genet 37 IssueID9 641–5 Occurrence Handle10.1136/jmg.37.9.641 Occurrence Handle10978352
N Suraweera A Duval M Reperant et al. (2002) ArticleTitleEvaluation of tumor microsatellite instability using five quasimonomorphic mononucleotide repeats and pentaplex PCR Gastroenterology 123 IssueID6 1804–11 Occurrence Handle10.1053/gast.2002.37070 Occurrence Handle12454837
XP Zhou JM Hoang YJ Li et al. (1998) ArticleTitleDetermination of the replication error phenotype in human tumors without the requirement for matching normal DNA by analysis of mononucleotide repeat microsatellites Genes Chromosomes Cancer 21 IssueID2 101–7 Occurrence Handle10.1002/(SICI)1098-2264(199802)21:2<101::AID-GCC4>3.0.CO;2-4 Occurrence Handle9491320
M. Perucho (1996) ArticleTitleCancer of the microsatellite mutator phenotype Biol Chem 377 IssueID11 675–84 Occurrence Handle8960367
R Pyatt RB Chadwick CK Johnson et al. (1999) ArticleTitlePolymorphic variation at the BAT-25 and BAT-26 loci in individuals of African origin. Implications for microsatellite instability testing. Am J Pathol 155 IssueID2 349–53 Occurrence Handle10433928
WS Samowitz ML Slattery JD Potter MF. Leppert (1999) ArticleTitleBAT-26 and BAT-40 instability in colorectal adenomas and carcinomas and germline polymorphisms Am J Pathol 154 IssueID6 1637–41 Occurrence Handle10362787
Bacher J, Flanagan, LA, Smalley, RL et al. Development of a fluorescent multiplex assay for detection of MSI-High tumors. Dis Markers 2004
MJ Berends Y Wu RH Sijmons et al. (2002) ArticleTitleMolecular and clinical characteristics of MSH6 variants: An analysis of 25 index carriers of a germline variant Am J Hum Genet 70 IssueID1 26–37 Occurrence Handle10.1086/337944 Occurrence Handle11709755
J Wijnen W Leeuw Particlede H Vasen et al. (1999) ArticleTitleFamilial endometrial cancer in female carriers of MSH6 germline mutations Nat Genet 23 IssueID2 142–4 Occurrence Handle10.1038/13773 Occurrence Handle10508506
Y Wu MJ Berends RG Mensink et al. (1999) ArticleTitleAssociation of hereditary nonpolyposis colorectal cancer-related tumors displaying low microsatellite instability with MSH6 germline mutations Am J Hum Genet 65 IssueID5 1291–8 Occurrence Handle10.1086/302612 Occurrence Handle10521294
A Wagner Y Hendriks EJ Meijers-Heijboer et al. (2001) ArticleTitleAtypical HNPCC owing to MSH6 germline mutations: Analysis of a large Dutch pedigree J Med Genet 38 IssueID5 318–22
GM Nash M Gimbel J Shia et al. (2003) ArticleTitleAutomated, multiplex assay for high-frequency microsatellite instability in colorectal cancer J Clin Oncol 21 IssueID16 3105–12 Occurrence Handle10.1200/JCO.2003.11.133 Occurrence Handle12915601
A Umar CR Boland JP Terdiman et al. (2004) ArticleTitleRevised Bethesda Guidelines for hereditary nonpolyposis colorectal cancer (Lynch syndrome) and microsatellite instability J Natl Cancer Inst 96 IssueID4 261–8 Occurrence Handle14970275
SS Wahlberg J Schmeits G Thomas et al. (2002) ArticleTitleEvaluation of microsatellite instability and immunohistochemistry for the prediction of germ-line MSH2 and MLH1 mutations in hereditary nonpolyposis colon cancer families Cancer Res 62 IssueID12 3485–92 Occurrence Handle12067992
G Moslein DJ Tester NM Lindor et al. (1996) ArticleTitleMicrosatellite instability and mutation analysis of hMSH2 and hMLH1 in patients with sporadic, familial and hereditary colorectal cancer Hum Mol Genet 5 IssueID9 1245–52 Occurrence Handle10.1093/hmg/5.9.1245 Occurrence Handle8872463
BV Bapat L Madlensky LK Temple et al. (1999) ArticleTitleFamily history characteristics, tumor microsatellite instability and germline MSH2 and MLH1 mutations in hereditary colorectal cancer Hum Genet 104 IssueID2 167–76 Occurrence Handle10.1007/s004390050931 Occurrence Handle10190329
M Christensen N Katballe F Wikman et al. (2002) ArticleTitleAntibody-based screening for hereditary nonpolyposis colorectal carcinoma compared with microsatellite analysis and sequencing Cancer 95 IssueID11 2422–30 Occurrence Handle10.1002/cncr.10979 Occurrence Handle12436451
T Liu S Wahlberg E Burek et al. (2000) ArticleTitleMicrosatellite instability as a predictor of a mutation in a DNA mismatch repair gene in familial colorectal cancer Genes Chromosomes Cancer 27 IssueID1 17–25 Occurrence Handle10.1002/(SICI)1098-2264(200001)27:1<17::AID-GCC3>3.0.CO;2-Y Occurrence Handle10564582
Y Hendriks P Franken JW Dierssen et al. (2003) ArticleTitleConventional and tissue microarray immunohistochemical expression analysis of mismatch repair in hereditary colorectal tumors Am J Pathol 162 IssueID2 469–77 Occurrence Handle12547705
SM Lipkin LS Rozek G Rennert et al. (2004) ArticleTitleThe MLH1 D132H variant is associated with susceptibility to sporadic colorectal cancer Nat Genet 36 IssueID7 694–9 Occurrence Handle10.1038/ng1374 Occurrence Handle15184898
W Muller LJ Burgart R Krause-Paulus et al. (2004) ArticleTitleThe 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 IssueID2 87–92 Occurrence Handle10.1023/A:1013840907881
B Vogelstein ER Fearon SR Hamilton et al. (1988) ArticleTitleGenetic alterations during colorectal-tumor development N Engl J Med 319 IssueID9 525–32 Occurrence Handle2841597
KW Kinzler B. Vogelstein (1996) ArticleTitleLessons from hereditary colorectal cancer Cell 87 IssueID2 159–70 Occurrence Handle8861899
HT Lynch T Smyrk JR. Jass (1995) ArticleTitleHereditary nonpolyposis colorectal cancer and colonic adenomas: Aggressive adenomas? Semin Surg Oncol 11 IssueID6 406–10 Occurrence Handle8607009
LA Aaltonen P Peltomaki JP Mecklin et al. (1994) ArticleTitleReplication errors in benign and malignant tumors from hereditary nonpolyposis colorectal cancer patients Cancer Res 54 IssueID7 1645–8 Occurrence Handle8137274
WS Samowitz ML. Slattery (1997) ArticleTitleMicrosatellite instability in colorectal adenomas Gastroenterology 112 IssueID5 1515–9 Occurrence Handle9136829
JR. Jass (2004) ArticleTitleHyperplastic polyps and colorectal cancer: Is there a link? Clin Gastroenterol Hepatol 2 IssueID1 1–8 Occurrence Handle10.1016/S1542-3565(03)00284-2 Occurrence Handle15017625
A Liljegren A Lindblom S Rotstein et al. (2003) ArticleTitlePrevalence and incidence of hyperplastic polyps and adenomas in familial colorectal cancer: Correlation between the two types of colon polyps Gut 52 IssueID8 1140–7 Occurrence Handle10.1136/gut.52.8.1140 Occurrence Handle12865272
H Iino JR Jass LA Simms et al. (1999) ArticleTitleDNA microsatellite instability in hyperplastic polyps, serrated adenomas, and mixed polyps: A mild mutator pathway for colorectal cancer? J Clin Pathol 52 IssueID1 5–9 Occurrence Handle10343605
FE Rijcken T Sluis Particlevan der H Hollema JH. Kleibeuker (2003) ArticleTitleHyperplastic polyps in hereditary nonpolyposis colorectal cancer Am J Gastroenterol 98 IssueID10 2306–11 Occurrence Handle10.1111/j.1572-0241.2003.07629.x Occurrence Handle14572584
Cunningham JM, Boardman LA, Burgart LJ, Thibodeau SN. Microsatellite instability in colon cancers. In Warren S (ed): Genetic Instabilities and Hereditary Neurological Diseases. Academic Press 1998: 791–807
P Peltomaki RA Lothe LA Aaltonen et al. (1993) ArticleTitleMicrosatellite instability is associated with tumors that characterize the hereditary non-polyposis colorectal carcinoma syndrome Cancer Res 53 IssueID24 5853–5 Occurrence Handle8261393
P. Peltomaki (2003) ArticleTitleRole of DNA mismatch repair defects in the pathogenesis of human cancer J Clin Oncol 21 IssueID6 1174–9 Occurrence Handle10.1200/JCO.2003.04.060 Occurrence Handle12637487
C Shannon J Kirk R Barnetson et al. (2003) ArticleTitleIncidence of microsatellite instability in synchronous tumors of the ovary and endometrium Clin Cancer Res 9 IssueID4 1387–92 Occurrence Handle12684409
CC Gurin MG Federici L Kang J. Boyd (1999) ArticleTitleCauses and consequences of microsatellite instability in endometrial carcinoma Cancer Res 59 IssueID2 462–6 Occurrence Handle9927063
MP Leon Particlede M Pedroni P Benatti et al. (1999) ArticleTitleHereditary colorectal cancer in the general population: From cancer registration to molecular diagnosis Gut 45 IssueID1 32–8 Occurrence Handle10369701
B Dieumegard S Grandjouan JC Sabourin et al. (2000) ArticleTitleExtensive molecular screening for hereditary non-polyposis colorectal cancer Br J Cancer 82 IssueID4 871–80 Occurrence Handle10.1054/bjoc.1999.1014 Occurrence Handle10732761
J Wijnen H Klift Particlevan der H Vasen et al. (1998) ArticleTitleMSH2 genomic deletions are a frequent cause of HNPCC Nat Genet 20 IssueID4 326–8 Occurrence Handle10.1038/3795 Occurrence Handle9843200
H Yan N Papadopoulos G Marra et al. (2000) ArticleTitleConversion of diploidy to haploidy Nature 403 IssueID6771 723–4 Occurrence Handle10.1038/35002251 Occurrence Handle10693791
CF Taylor RS Charlton J Burn et al. (2003) ArticleTitleGenomic deletions in MSH2 or MLH1 are a frequent cause of hereditary non-polyposis colorectal cancer: Identification of novel and recurrent deletions by MLPA Hum Mutat 22 IssueID6 428–33 Occurrence Handle10.1002/humu.10291 Occurrence Handle14635101
A Hemminki JP Mecklin H Jarvinen et al. (2000) ArticleTitleMicrosatellite instability is a favorable prognostic indicator in patients with colorectal cancer receiving chemotherapy Gastroenterology 119 IssueID4 921–8 Occurrence Handle10.1053/gast.2000.18161 Occurrence Handle11040179
CM Ribic DJ Sargent MJ Moore et al. (2003) ArticleTitleTumor microsatellite-instability status as a predictor of benefit from fluorouracil-based adjuvant chemotherapy for colon cancer N Engl J Med 349 IssueID3 247–57 Occurrence Handle10.1056/NEJMoa022289 Occurrence Handle12867608
JM Carethers EJ Smith CA Behling et al. (2004) ArticleTitleUse of 5-fluorouracil and survival in patients with microsatellite-unstable colorectal cancer Gastroenterology 126 IssueID2 394–401 Occurrence Handle10.1053/j.gastro.2003.12.023 Occurrence Handle14762775
CN Arnold A Goel CR. Boland (2003) ArticleTitleRole of hMLH1 promoter hypermethylation in drug resistance to 5-fluorouracil in colorectal cancer cell lines Int J Cancer 106 IssueID1 66–73 Occurrence Handle10.1002/ijc.11176 Occurrence Handle12794758
Author information
Authors and Affiliations
Corresponding author
Rights and permissions
About this article
Cite this article
Baudhuin, L.M., Burgart, L.J., Leontovich, O. et al. Use of Microsatellite Instability and Immunohistochemistry Testing for the Identification of Individuals at Risk for Lynch Syndrome. Familial Cancer 4, 255–265 (2005). https://doi.org/10.1007/s10689-004-1447-6
Received:
Accepted:
Issue Date:
DOI: https://doi.org/10.1007/s10689-004-1447-6