[Microsatellite instability. A new predictive marker (?)].
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.
Dietmaier
W
W
Institut für Pathologie/Zentrum für molekularpathologische Diagnostik, Universität Regensburg, Franz-Josef-Strauss-Allee 11, 93053 Regensburg. wolfgang.dietmaier@klinik.uni-regensburg.de
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
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
J Clin Oncol. 2005 Jan 20;23(3):609-18
15659508
Gastroenterology. 2004 Dec;127(6):1678-84
15578504
Cancer Res. 1997 Nov 1;57(21):4749-56
9354436
Int J Cancer. 2006 May 1;118(9):2247-54
16331619
Eur J Cancer. 2009 Jul;45(10):1890-6
19427194
J Clin Oncol. 2009 Apr 10;27(11):1814-21
19273709
Mol Pharmacol. 1985 Jul;28(1):51-5
3894930
Nat Rev Clin Oncol. 2010 Apr;7(4):197-208
20177404
N Engl J Med. 2004 Jun 3;350(23):2343-51
15175436
Lancet. 2000 May 20;355(9217):1745-50
10832824
N Engl J Med. 2003 Jul 17;349(3):247-57
12867608
Cancer Res. 1998 Nov 15;58(22):5248-57
9823339
Cancer Res. 2003 Sep 15;63(18):5738-44
14522894
Cancer Res. 2001 Jul 1;61(13):5193-201
11431359
Curr Opin Oncol. 2009 Jul;21(4):369-73
19444104
Gut. 2008 Jul;57(7):941-50
18364437
Gastroenterology. 1999 Jul;117(1):123-31
10381918
J Clin Oncol. 2009 Jul 1;27(19):3109-16
19451431
J Clin Oncol. 2010 Jan 20;28(3):466-74
20008640