Current Gastroenterology Reports

, Volume 7, Issue 5, pp 412–420

Lynch syndrome (hereditary non-polyposis colorectal cancer): Current concepts and approaches to management

  • Luigi Ricciardiello
  • C. Richard Boland


Colorectal cancer is among the most frequent causes of cancer death worldwide. An inherited predisposition to cancer of the colon and other organs, Lynch syndrome—also called hereditary non-polyposis colorectal cancer—is probably the most frequent cause of hereditary cancer and is often found in a colon cancer patient and traced through other family members. However, this syndrome is not only characterized by the early onset of colon cancers but also by a predisposition to a constellation of extraintestinal cancers that tend to be misdiagnosed. With new diagnostic technologies, the incidence of familial/inherited versus sporadic cases may appear to increase, due to the recognition of cancers in families that do not fulfill clinical guidelines developed prior to knowledge of the genetic basis of this disease. We now have the ability and the responsibility to detect and prevent this disease, and equally important, to direct patients to specifically targeted treatment. Specialists should be aware of the significance of inherited colon cancer and should become familiar with the molecular diagnostic tests now widely available.


Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.

References and Recommended Reading

  1. 1.
    Boland CR: Evolution of the nomenclature for hereditary colorectal cancer. Fam Cancer 2005, 4:211–217.PubMedCrossRefGoogle Scholar
  2. 2.
    Marra G, Boland CR: Hereditary nonpolyposis colorectal cancer: the syndrome, the genes, and historical perspectives. J Natl Cancer Inst 1995, 87:1114–1125.PubMedCrossRefGoogle Scholar
  3. 3.
    Lynch HT, Krush AJ: Cancer family "G" revisited: 1895–1970. Cancer 1971, 27:1505–1511.PubMedCrossRefGoogle Scholar
  4. 4.
    Lynch HT, Shaw MW, Magnuson CW, et al.: Hereditary factors in cancer: study of two large Midwestern kindreds. Arch Intern Med 1966, 117:206–212.PubMedCrossRefGoogle Scholar
  5. 5.
    Boland CR, Troncale FJ: Familial colonic cancer without antecedent polyposis. Ann Intern Med 1984, 100:700–701.PubMedGoogle Scholar
  6. 6.
    Lynch HT, Kimberling W, Albano WA, et al.: Hereditary nonpolyposis colorectal cancer (Lynch syndromes I and II). I. Clinical description of resource. Cancer 1985, 56:934–938.PubMedCrossRefGoogle Scholar
  7. 7.
    Mecklin JP, Sipponen P, Jarvinen HJ: Histopathology of colorectal carcinomas and adenomas in cancer family syndrome. Dis Colon Rectum 1986, 29:849–853.PubMedCrossRefGoogle Scholar
  8. 8.
    Ponti G, Losi L, Di Gregorio C, et al.: Identification of Muir-Torre syndrome among patients with sebaceous tumors and keratoacanthomas: role of clinical features, microsatellite instability, and immunohistochemistry. Cancer 2005, 103:1018–1025.PubMedCrossRefGoogle Scholar
  9. 9.
    Vasen HF, Mecklin JP, Khan PM, Lynch HT: The international collaborative group on hereditary non-polyposis colorectal cancer (ICG-HNPCC). Dis Colon Rectum 1991, 34:424–425.PubMedCrossRefGoogle Scholar
  10. 10.
    Vasen HF, Watson P, Mecklin JP, Lynch HT: New clinical criteria for hereditary nonpolyposis colorectal cancer (HNPCC, Lynch syndrome) proposed by the International Collaborative group on HNPCC. Gastroenterology 1999, 116:1453–1456.PubMedCrossRefGoogle Scholar
  11. 11.
    Ionov Y, Peinado MA, Malkhosyan S, et al.: Ubiquitous somatic mutations in simple repeated sequences reveal a new mechanism for colonic carcinogenesis. Nature 1993, 363:558–561.PubMedCrossRefGoogle Scholar
  12. 12.
    Thibodeau SN, Bren G, Schaid D: Microsatellite instability in cancer of the proximal colon. Science 1993, 260:816–819.PubMedCrossRefGoogle Scholar
  13. 13.
    Aaltonen LA, Peltomaki P, Leach FS, et al.: Clues to the pathogenesis of familial colorectal cancer. Science 1993, 260:812–816.PubMedCrossRefGoogle Scholar
  14. 14.
    Fishel R: The selection for mismatch repair defects in hereditary nonpolyposis colorectal cancer: revising the mutator hypothesis. Cancer Res 2001, 61:7369–7374.PubMedGoogle Scholar
  15. 15.
    Bronner CE, Baker SM, Morrison PT, et al.: Mutation in the DNA mismatch repair gene homologue hMLH1 is associated with hereditary non-polyposis colon cancer. Nature 1994, 368:258–261.PubMedCrossRefGoogle Scholar
  16. 16.
    Edelmann W, Yang K, Umar A, et al.: Mutation in the mismatch repair gene Msh6 causes cancer susceptibility. Cell 1997, 91:467–477.PubMedCrossRefGoogle Scholar
  17. 17.
    Fishel R, Lescoe MK, Rao MR, et al.: The human mutator gene homolog MSH2 and its association with hereditary nonpolyposis colon cancer. Cell 1994, 77:167.PubMedCrossRefGoogle Scholar
  18. 18.
    Kolodner RD, Tytell JD, Schmeits JL, et al.: Germ-line msh6 mutations in colorectal cancer families. Cancer Res 1999, 59:5068–5074.PubMedGoogle Scholar
  19. 19.
    Leach FS, Nicolaides NC, Papadopoulos N, et al.: Mutations of a mutS homolog in hereditary nonpolyposis colorectal cancer. Cell 1993, 75(6):1215–1225.PubMedCrossRefGoogle Scholar
  20. 20.
    Peltomaki P, Aaltonen LA, Sistonen P, et al.: Genetic mapping of a locus predisposing to human colorectal cancer. Science 1993, 260:810–812.PubMedCrossRefGoogle Scholar
  21. 21.
    Wu Y, Berends MJ, Post JG, Mensink RG, et al.: Germlinemutations of EXO1 gene in patients with hereditary nonpolyposis colorectal cancer (HNPCC) and atypical HNPCC forms. Gastroenterology 2001, 120:1580–1587.PubMedCrossRefGoogle Scholar
  22. 22.
    Hendriks YM, Wagner A, Morreau H, et al.: Cancer risk in hereditary nonpolyposis colorectal cancer due to MSH6 mutations: impact on counseling and surveillance. Gastroenterology 2004, 127:17–25.PubMedCrossRefGoogle Scholar
  23. 23.
    Nakagawa H, Lockman JC, Frankel WL, et al.: Mismatch repair gene PMS2: disease-causing germline mutations are frequent in patients whose tumors stain negative for PMS2 protein, but paralogous genes obscure mutation detection and interpretation. Cancer Res 2004, 64(14):4721–4727.PubMedCrossRefGoogle Scholar
  24. 24.
    Truninger K, Menigatti M, Luz J, et al.: Immunohistochemical analysis reveals high frequency of PMS2 defects in colorectal cancer. Gastroenterology 2005, 128:1160–1171. This paper highlights the possible role of hPMS2 in causing an attenuated form of Lynch syndrome that may be difficult to diagnose.PubMedCrossRefGoogle Scholar
  25. 25.
    Boland CR, Fishel R: Form, function, proteins and basketball. Gastroenterology 2005, 129:751–755.PubMedCrossRefGoogle Scholar
  26. 26.
    Loeb LA: Mutator phenotype may be required for multistage carcinogenesis. Cancer Res 1991, 51:3075–3079.PubMedGoogle Scholar
  27. 27.
    Loeb LA: Microsatellite instability: marker of a mutator phenotype in cancer. Cancer Res 1994, 54:5059–5063.PubMedGoogle Scholar
  28. 28.
    Markowitz S, Wang J, Myeroff L, et al.: Inactivation of the type II TGF-beta receptor in colon cancer cells with microsatellite instability. Science 1995, 268:1336–1338.PubMedCrossRefGoogle Scholar
  29. 29.
    Rampino N, Yamamoto H, Ionov Y, et al.: Somatic frameshift mutations in the BAX gene in colon cancers of the microsatellite mutator phenotype. Science 1997, 275:967–969.PubMedCrossRefGoogle Scholar
  30. 30.
    Souza RF, Appel R, Yin J, et al.: Microsatellite instability in the insulin-like growth factor II receptor gene in gastrointestinal tumours. Nat Genet 1996, 14:255–257.PubMedCrossRefGoogle Scholar
  31. 31.
    Duval A, Hamelin R: Mutations at coding repeat sequences in mismatch repair-deficient human cancers: toward a new concept of target genes for instability. Cancer Res 2002, 62:2447–2454.PubMedGoogle Scholar
  32. 32.
    Lengauer C: Aneuploidy and genetic instability in cancer. Semin Cancer Biol 2005, 15:43–49.PubMedCrossRefGoogle Scholar
  33. 33.
    Syngal S, Fox EA, Li C, et al.: Interpretation of genetic test results for hereditary nonpolyposis colorectal cancer: implications for clinical predisposition testing. JAMA 1999, 282:247–253.PubMedCrossRefGoogle Scholar
  34. 34.
    Lindor NM, Rabe K, Petersen GM, et al.: Lower cancer incidence in Amsterdam-I criteria families without mismatch repair deficiency: familial colorectal cancer type X. JAMA 2005, 293:1979–1985. This large collaborative study of carefully studied colon cancer families demonstrates that 60% have an identifiable mutation in a DNA MMR gene (ie, have Lynch syndrome) but that 40% do not ("syndrome X").PubMedCrossRefGoogle Scholar
  35. 35.
    Boland CR, Thibodeau SN, Hamilton SR, et al.: 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 1998, 58:5248–5257.PubMedGoogle Scholar
  36. 36.
    Rodriguez-Bigas MA, Boland CR, Hamilton SR, et al.: A National Cancer Institute Workshop on Hereditary Nonpolyposis Colorectal Cancer Syndrome: meeting highlights and Bethesda guidelines. J Natl Cancer Inst 1997, 89:1758–1762.PubMedCrossRefGoogle Scholar
  37. 37.
    Umar A, Boland CR, Terdiman JP, J et al.: Revised Bethesda Guidelines for hereditary nonpolyposis colorectal cancer (Lynch syndrome) and microsatellite instability. J Natl Cancer Inst 2004, 96:261–268.PubMedCrossRefGoogle Scholar
  38. 38.
    Jass JR: HNPCC and sporadic MSI-H colorectal cancer: a review of the morphological similarities and differences. Fam Cancer 2004, 3:93–100.PubMedCrossRefGoogle Scholar
  39. 39.
    Pinol V, Castells A, Andreu M, et al.: Accuracy of revised Bethesda guidelines, microsatellite instability, and immunohistochemistry for the identification of patients with hereditary nonpolyposis colorectal cancer. JAMA 2005, 293:1986–1994.PubMedCrossRefGoogle Scholar
  40. 40.
    Syngal S, Fox EA, Eng C, et al.: Sensitivity and specificity of clinical criteria for hereditary non-polyposis colorectal cancer associated mutations in MSH2 and MLH1. J Med Genet 2000, 37:641–645.PubMedCrossRefGoogle Scholar
  41. 41.
    Wahlberg SS, Schmeits J, Thomas G, et al.: Evaluation of microsatellite instability and immunohistochemistry for the prediction of germ-line MSH2 and MLH1 mutations in hereditary nonpolyposis colon cancer families. Cancer Res 2002, 62:3485–3492.PubMedGoogle Scholar
  42. 42.
    Suraweera N, Duval A, Reperant M, et al.: Evaluation of tumor microsatellite instability using five quasimonomorphic mononucleotide repeats and pentaplex PCR. Gastroenterology 2002, 123:1804–1811.PubMedCrossRefGoogle Scholar
  43. 43.
    Hampel H, Frankel WL, Martin E, et al.: Screening for the Lynch syndrome (hereditary nonpolyposis colorectal cancer). N Engl J Med 2005, 352:1851–1860. Suggests that the use of immunohistochemistry may be a practical alternative to MSI testing to find Lynch syndrome families.PubMedCrossRefGoogle Scholar
  44. 44.
    Lindor NM, Burgart LJ, Leontovich O, et al.: Immunohistochemistry versus microsatellite instability testing in phenotyping colorectal tumors. J Clin Oncol 2002, 20:1043–1048.PubMedCrossRefGoogle Scholar
  45. 45.
    Bala S, Peltomaki P: CYCLIN D1 as a genetic modifier in hereditary nonpolyposis colorectal cancer. Cancer Res 2001, 61:6042–6045.PubMedGoogle Scholar
  46. 46.
    Frazier ML, O’Donnell FT, Kong S, et al.: Age-associated risk of cancer among individuals with N-acetyltransferase 2 (NAT2) mutations and mutations in DNA mismatch repair genes. Cancer Res 2001, 61:1269–1271.PubMedGoogle Scholar
  47. 47.
    Kong S, Amos CI, Luthra R, et al.: Effects of cyclin D1 polymorphism on age of onset of hereditary nonpolyposis colorectal cancer. Cancer Res 2000, 60:249–252.PubMedGoogle Scholar
  48. 48.
    Maillet P, Chappuis PO, Vaudan G, et al.: A polymorphism in the ATM gene modulates the penetrance of hereditary nonpolyposis colorectal cancer. Int J Cancer 2000, 88:928–931.PubMedCrossRefGoogle Scholar
  49. 49.
    Jones JS, Chi X, Gu X, et al.: p53 polymorphism and age of onset of hereditary nonpolyposis colorectal cancer in a Caucasian population. Clin Cancer Res 2004, 10:5845–5849.PubMedCrossRefGoogle Scholar
  50. 50.
    Wu Y, Berends MJ, Sijmons RH, et al.: A role for MLH3 in hereditary nonpolyposis colorectal cancer. Nat Genet 2001, 29:137–138.PubMedCrossRefGoogle Scholar
  51. 51.
    Lipkin SM, Wang V, Jacoby R, et al.: MLH3: a DNA mismatch repair gene associated with mammalian microsatellite instability. Nat Genet 2000, 24:27–35.PubMedCrossRefGoogle Scholar
  52. 52.
    Lu SL, Kawabata M, Imamura T, et al.: HNPCC associated with germline mutation in the TGF-beta type II receptor gene. Nat Genet 1998, 19:17–18.PubMedCrossRefGoogle Scholar
  53. 53.
    Bian Y, Caldes T, Wijnen J, et al.: TGFBR1*6A may contribute to hereditary colorectal cancer. J Clin Oncol 2005, 23:3074–3078.PubMedCrossRefGoogle Scholar
  54. 54.
    Young J, Barker MA, Simms LA, et al.: Evidence for BRAF mutation and variable levels of microsatellite instability in a syndrome of familial colorectal cancer. Clin Gastroenterol Hepatol 2005, 3:254–263. This provocative report suggests a novel phenotype for familial colorectal cancer, which is distinct from Lynch syndrome.PubMedCrossRefGoogle Scholar
  55. 55.
    Jass JR, Whitehall VL, Young J, Leggett BA: Emerging concepts in colorectal neoplasia. Gastroenterology 2002, 123:862–876.PubMedCrossRefGoogle Scholar
  56. 56.
    Bandipalliam P, Garber J, Kolodner RD, Syngal S: Clinical presentation correlates with the type of mismatch repair gene involved in hereditary nonpolyposis colon cancer. Gastroenterology 2004, 126:936–937. The authors suggest that hMLH1 germline mutations are associated with Lynch syndrome I, whereas mutations of hMHS2 are associated with Lynch syndrome II.PubMedCrossRefGoogle Scholar
  57. 57.
    Lynch HT, Coronel SM, Okimoto R, et al.: A founder mutation of the MSH2 gene and hereditary nonpolyposis colorectal cancer in the United States. JAMA 2004, 291:718–724.PubMedCrossRefGoogle Scholar
  58. 58.
    Wijnen J, van der KH, Vasen H, et al.: MSH2 genomic deletions are a frequent cause of HNPCC. Nat Genet 1998, 20:326–328.PubMedCrossRefGoogle Scholar
  59. 59.
    Casey G, Lindor NM, Papadopoulos N, et al.: Conversion analysis for mutation detection in MLH1 and MSH2 in patients with colorectal cancer. JAMA 2005, 293:799–809. This report underscores the technical challenges to finding all of the mutations that cause Lynch syndrome.PubMedCrossRefGoogle Scholar
  60. 60.
    Whiteside D, McLeod R, Graham G, et al.: A homozygous germ-line mutation in the human MSH2 gene predisposes to hematological malignancy and multiple cafe-au-lait spots. Cancer Res 2002, 62:359–362.PubMedGoogle Scholar
  61. 61.
    Ricciardone MD, Ozcelik T, Cevher B, et al.: Human MLH1 deficiency predisposes to hematological malignancy and neurofibromatosis type 1. Cancer Res 1999, 59:290–293.PubMedGoogle Scholar
  62. 62.
    Bougeard G, Charbonnier F, Moerman A, et al.: Early onset brain tumor and lymphoma in MSH2-deficient children. Am J Hum Genet 2003, 72:213–216.PubMedCrossRefGoogle Scholar
  63. 63.
    Trimbath JD, Petersen GM, Erdman SH, et al.: Cafe-au-lait spots and early onset colorectal neoplasia: a variant of HNPCC? Fam Cancer 2001, 1:101–105.PubMedCrossRefGoogle Scholar
  64. 64.
    Mangold E, Pagenstecher C, Leister M, et al.: A genotype-phenotype correlation in HNPCC: strong predominance of msh2 mutations in 41 patients with Muir-Torre syndrome. J Med Genet 2004, 41:567–572.PubMedCrossRefGoogle Scholar
  65. 65.
    Lynch HT, Lynch PM, Pester J, Fusaro RM: The cancer family syndrome. Rare cutaneous phenotypic linkage of Torre’s syndrome. Arch Intern Med 1981, 141:607–611.PubMedCrossRefGoogle Scholar
  66. 66.
    Entius MM, Keller JJ, Drillenburg P, et al.: Microsatellite instability and expression of hMLH-1 and hMSH-2 in sebaceous gland carcinomas as markers for Muir-Torre syndrome. Clin Cancer Res 2000, 6:1784–1789.PubMedGoogle Scholar
  67. 67.
    Jager AC, Bisgaard ML, Myrhoj T, et al.: Reduced frequency of extracolonic cancers in hereditary nonpolyposis colorectal cancer families with monoallelic hMLH1 expression. Am J Hum Genet 1997, 61:129–138.PubMedGoogle Scholar
  68. 68.
    Lipkin SM, Rozek LS, Rennert G, et al.: The MLH1 D132H variant is associated with susceptibility to sporadic colorectal cancer. Nat Genet 2004, 36:694–699.PubMedCrossRefGoogle Scholar
  69. 69.
    Gallinger S, Aronson M, Shayan K, et al.: Gastrointestinal cancers and neurofibromatosis type 1 features in children with a germline homozygous MLH1 mutation. Gastroenterology 2004, 126:576–585.PubMedCrossRefGoogle Scholar
  70. 70.
    Scheenstra R, Rijcken FE, Koornstra JJ, et al.: Rapidly progressive adenomatous polyposis in a patient with germline mutations in both the APC and MLH1 genes: the worst of two worlds. Gut 2003, 52:898–899.PubMedCrossRefGoogle Scholar
  71. 71.
    Herman JG, Umar A, Polyak K, et al.: Incidence and functional consequences of hMLH1 promoter hypermethylation in colorectal carcinoma. Proc Natl Acad Sci U S A 1998, 95:6870–6875.PubMedCrossRefGoogle Scholar
  72. 72.
    Cunningham JM, Christensen ER, Tester DJ, et al.: Hypermethylation of the hMLH1 promoter in colon cancer with microsatellite instability. Cancer Res 1998, 58:3455–3460.PubMedGoogle Scholar
  73. 73.
    Gryfe R, Kim H, Hsieh ET, et al.: Tumor microsatellite instability and clinical outcome in young patients with colorectal cancer. N Engl J Med 2000, 342:69–77.PubMedCrossRefGoogle Scholar
  74. 74.
    Miyakura Y, Sugano K, Konishi F, et al.: Extensive methylation of hMLH1 promoter region predominates in proximal colon cancer with microsatellite instability. Gastroenterology 2001, 121:1300–1309.PubMedCrossRefGoogle Scholar
  75. 75.
    Samowitz WS, Curtin K, Ma KN, et al.: Microsatellite instability in sporadic colon cancer is associated with an improved prognosis at the population level. Cancer Epidemiol Biomarkers Prev 2001, 10:917–923.PubMedGoogle Scholar
  76. 76.
    Sankila R, Aaltonen LA, Jarvinen HJ, Mecklin JP: Better survival rates in patients with MLH1-associated hereditary colorectal cancer. Gastroenterology 1996, 110:682–687.PubMedCrossRefGoogle Scholar
  77. 77.
    Ward R, Meagher A, Tomlinson I, et al.: Microsatellite instability and the clinicopathological features of sporadic colorectal cancer. Gut 2001, 48:821–829.PubMedCrossRefGoogle Scholar
  78. 78.
    Nagasaka T, Sasamoto H, Notohara K, et al.: Colorectal cancer with mutation in BRAF, KRAS, and wild-type with respect to both oncogenes showing different patterns of DNA methylation. J Clin Oncol 2004, 22:4584–4594.PubMedCrossRefGoogle Scholar
  79. 79.
    Chang DK, Ricciardiello L, Goel A, et al.: Steady-state regulation of the human DNA mismatch repair system. J Biol Chem 2000, 275:18424–18431.PubMedCrossRefGoogle Scholar
  80. 80.
    Giardiello FM, Brensinger JD, Petersen GM: AGA technical review on hereditary colorectal cancer and genetic testing. Gastroenterology 2001, 121:198–213.PubMedCrossRefGoogle Scholar
  81. 81.
    Vasen HF, Nagengast FM, Khan PM: Interval cancers in hereditary non-polyposis colorectal cancer (Lynch syndrome). Lancet 1995, 345:1183–1184. This brief but important report indicates that some patients with Lynch syndrome who are screened every 3 years with colonoscopy will still develop a (curable) cancer in the interval between examinations.PubMedCrossRefGoogle Scholar
  82. 82.
    Carethers JM, Chauhan DP, Fink D, et al.: Mismatch repair proficiency and in vitro response to 5-fluorouracil. Gastroenterology 1999, 117:123–131.PubMedCrossRefGoogle Scholar
  83. 83.
    Arnold CN, Goel A, Boland CR: Role of hMLH1 promoter hypermethylation in drug resistance to 5-fluorouracil in colorectal cancer cell lines. Int J Cancer 2003, 106:66–73.PubMedCrossRefGoogle Scholar
  84. 84.
    Ribic CM, Sargent DJ, Moore MJ, et al.: Tumor microsatelliteinstability status as a predictor of benefit from fluorouracilbased adjuvant chemotherapy for colon cancer. N Engl J Med 2003, 349:247–257. This trial demonstrates that stage III colorectal cancer patients with MSI in the tumor do not derive benefit from adjuvant 5-FU and may be harmed by treatment.PubMedCrossRefGoogle Scholar
  85. 85.
    Carethers JM, Smith EJ, Behling CA, et al.: Use of 5-fluorouracil and survival in patients with microsatellite-unstable colorectal cancer. Gastroenterology 2004, 126:394–401.PubMedCrossRefGoogle Scholar
  86. 86.
    Ricciardiello L, Ceccarelli C, Angiolini G, et al.: High thymidylate synthase expression in colorectal cancer with microsatellite instability: implications for chemotherapeutic strategies. Clin Cancer Res 2005, 11:4234–4240.PubMedCrossRefGoogle Scholar
  87. 87.
    Leichman CG, Lenz HJ, Leichman L, et al.: Quantitation of intratumoral thymidylate synthase expression predicts for disseminated colorectal cancer response and resistance to protracted-infusion fluorouracil and weekly leucovorin. J Clin Oncol 1997, 15:3223–3229.PubMedGoogle Scholar
  88. 88.
    Lenz HJ, Leichman CG, Danenberg KD, et al.: Thymidylate synthase mRNA level in adenocarcinoma of the stomach: a predictor for primary tumor response and overall survival. J Clin Oncol 1996, 14:176–182.PubMedGoogle Scholar
  89. 89.
    Tajima A, Hess MT, Cabrera BL, et al.: The mismatch repair complex hMutS alpha recognizes 5-fluorouracil-modified DNA: implications for chemosensitivity and resistance. Gastroenterology 2004, 127:1678–1684.PubMedCrossRefGoogle Scholar
  90. 90.
    Fallik D, Borrini F, Boige V, et al.: Microsatellite instability is a predictive factor of the tumor response to irinotecan in patients with advanced colorectal cancer. Cancer Res 2003, 63:5738–5744.PubMedGoogle Scholar

Copyright information

© Current Science Inc 2005

Authors and Affiliations

  • Luigi Ricciardiello
    • 1
  • C. Richard Boland
    • 1
  1. 1.Gastrointestinal Cancer Research Laboratory, Department of Medicine, Division of Gastroenterology, H-250Baylor University Medical CenterDallasUSA

Personalised recommendations