title: [Microsatellite instability. A new predictive marker (?)].
abstract: Microsatellite instability (MSI) is a hallmark of hereditary non-polyposis colorectal cancer (HNPCC), but also occurs in about 12%-15% of sporadic colorectal cancer (CRC) where it is a consequence of an epigenetic inactivation of MLH1. High frequency MSI (MSI-H; i.e. at least two of five specified microsatellite markers show instability) was shown in a large meta-analysis and in recent trials to be a positive prognostic marker for overall survival in CRC. MSI-H or mismatch repair deficiency (MMRD) was also shown to be a marker for ineffectiveness of adjuvant 5-fluorouracil (5-FU) based chemotherapy in CRC. At present, there are no guidelines defining the need for microsatellite analysis before chemotherapy. However, studies published to date provide data suggesting that MSI-H CRC patients should not receive adjuvant chemotherapy, with the exception of patients with other factors or poor prognosis (e.g. T4 tumors, G3/G4 status, blood or lymphatic vessel invasion). MSI or MMRD testing can contribute to a more individualized therapy of CRC and should be performed prior to planned 5-FU monotherapy or adjuvant chemotherapy in a non-metastatic setting.
authors.affiliation: Institut für Pathologie/Zentrum für molekularpathologische Diagnostik, Universität Regensburg, Franz-Josef-Strauss-Allee 11, 93053 Regensburg. wolfgang.dietmaier@klinik.uni-regensburg.de
authors.forename: W
authors.initials: W
authors.lastname: Dietmaier
mesh_terms: D048868:Adaptor Proteins, Signal Transducing / Q000235:genetics; D000964:Antimetabolites, Antineoplastic / Q000627:therapeutic use; D014408:Biomarkers, Tumor / Q000235:genetics*; D017024:Chemotherapy, Adjuvant; D015179:Colorectal Neoplasms / Q000188:drug therapy / Q000235:genetics* / Q000473:pathology*; D003123:Colorectal Neoplasms, Hereditary Nonpolyposis / Q000188:drug therapy / Q000235:genetics* / Q000473:pathology*; D053843:DNA Mismatch Repair / Q000235:genetics; D019008:Drug Resistance, Neoplasm; D044127:Epigenesis, Genetic; D005472:Fluorouracil / Q000627:therapeutic use; D006801:Humans; D053842:Microsatellite Instability; D000070957:MutL Protein Homolog 1; D009367:Neoplasm Staging; D009687:Nuclear Proteins / Q000235:genetics; D011379:Prognosis
chemical_list: D048868:Adaptor Proteins, Signal Transducing; D000964:Antimetabolites, Antineoplastic; D014408:Biomarkers, Tumor; C501486:MLH1 protein, human; D009687:Nuclear Proteins; D000070957:MutL Protein Homolog 1; D005472:Fluorouracil
references.citation: J Clin Oncol. 2005 Jan 20;23(3):609-18
references.pmid: 15659508
references.citation: Gastroenterology. 2004 Dec;127(6):1678-84
references.pmid: 15578504
references.citation: Cancer Res. 1997 Nov 1;57(21):4749-56
references.pmid: 9354436
references.citation: Int J Cancer. 2006 May 1;118(9):2247-54
references.pmid: 16331619
references.citation: Eur J Cancer. 2009 Jul;45(10):1890-6
references.pmid: 19427194
references.citation: J Clin Oncol. 2009 Apr 10;27(11):1814-21
references.pmid: 19273709
references.citation: Mol Pharmacol. 1985 Jul;28(1):51-5
references.pmid: 3894930
references.citation: Nat Rev Clin Oncol. 2010 Apr;7(4):197-208
references.pmid: 20177404
references.citation: N Engl J Med. 2004 Jun 3;350(23):2343-51
references.pmid: 15175436
references.citation: Lancet. 2000 May 20;355(9217):1745-50
references.pmid: 10832824
references.citation: N Engl J Med. 2003 Jul 17;349(3):247-57
references.pmid: 12867608
references.citation: Cancer Res. 1998 Nov 15;58(22):5248-57
references.pmid: 9823339
references.citation: Cancer Res. 2003 Sep 15;63(18):5738-44
references.pmid: 14522894
references.citation: Cancer Res. 2001 Jul 1;61(13):5193-201
references.pmid: 11431359
references.citation: Curr Opin Oncol. 2009 Jul;21(4):369-73
references.pmid: 19444104
references.citation: Gut. 2008 Jul;57(7):941-50
references.pmid: 18364437
references.citation: Gastroenterology. 1999 Jul;117(1):123-31
references.pmid: 10381918
references.citation: J Clin Oncol. 2009 Jul 1;27(19):3109-16
references.pmid: 19451431
references.citation: J Clin Oncol. 2010 Jan 20;28(3):466-74
references.pmid: 20008640