Microsatellite instability in the management of colorectal cancer

Abstract

Microsatellite instability (MSI) is a form of genetic instability caused by alterations in the DNA mismatch repair system. Approximately 15% of colorectal cancers display MSI due to a germline mutation in one of the mismatch repair genes (MLH1, MSH2, MSH6 and PMS2) or to epigenetic silencing of MLH1. Colorectal cancers with MSI have distinctive features, including a tendency to arise in the proximal colon, poor differentiation, lymphocytic infiltration and mucinous or signet-ring histology. Patients with MSI tumors appear to have a better prognosis than those with microsatellite stable tumors, but curiously the responses to 5-fluorouracil-based chemotherapy regimens are poorer with MSI tumors. Preliminary data suggest possible advantages of irinotecan-based regimens, but these findings need validation in well-designed clinical trials.

Keywords::

• colorectal cancer
• Lynch syndrome
• microsatellite instability
• mismatch repair genes
• predictive marker
• prognostic marker

Financial & competing interests disclosure

The authors have no relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript. This includes employment, consultancies, honoraria, stock ownership or options, expert testimony, grants or patents received or pending, or royalties.

No writing assistance was utilized in the production of this manuscript.

Notes

^†Syndrome-associated tumors include colorectal, endometrial, ovarian, stomach, small bowel, ureter or renal pelvis, biliary tract, pancreas, brain and sebaceous gland.

^‡Presence of tumor-infiltrating lymphocytes, Crohn’s disease-like lymphocytic reaction, mucinous/signet-ring differentiation or medullary growth pattern.

FAP: Familial adenomatous polyposis; HNPCC: Hereditary nonpolyposis colorectal cancer; MSI-H: Microsatellite instability-high.