Copyright ©The Author(s) 2016.
World J Gastroenterol. Apr 7, 2016; 22(13): 3516-3530
Published online Apr 7, 2016. doi: 10.3748/wjg.v22.i13.3516
Table 1 Proposed[80] colorectal cancer classification
Subtype 1MSI-H++-
Subtype 2MSS or MSI-L++-
Subtype 3MSS or MSI-L--+
Subtype 4MSS or MSI-L---
Subtype 5MSI-H---
Subtype 1MSI+++/-
Subtype 2MSS+/-+-
Subtype 3MSS+/--+
Subtype 4MSS+/---
Subtype 5MSI--+/-
Table 2 Summary of the treatment implications of genetic alterations in colorectal cancer
Molecular markerImplications for CRC treatment
KRAS mutationBroadly studied in metastatic CRC
The most predictive biomarker for no response to anti-EGFR, either alone or with CT
Worse OS when oxaliplatin is the first-line treatment
Irinotecan efficacy is controversial; it may have better effects in stage II and III CRC
BRAF mutationOverall, no predictive power for CT response
No predictive power for response to 5-FU plus irinotecan/oxaliplatin or to 5-FU alone in stage II disease
A trend toward better survival with 5-FU plus irinotecan in stage III disease
Effects of anti-EGFR therapy are controversial, although most studies show a poor response
Some studies show no differences in OS/DFS with FOLFOX-panitumumab or with FOLFIRI-cetuximab treatment
Resistance to BRAF inhibitors
CIMPCT results are controversial
5-FU improves DFS and OS in some studies; in others, survival is reduced
One study shows the benefits of 5-FU plus irinotecan in CIMP tumors after stratification by MMR status. CIMP was more strongly associated than MMR status with a better response to irinotecan
The use of 5-FU in CIMP tumors is not currently recommended
To date, no clinical trials have evaluated the response of CIMP tumors to anti-EGFR therapy
MMRPrognosis is intrinsically better for MSI CRC, but MSS tumors show a better response to CT
5-FU improves both DFS and OS in stage II and III MSS CRC but not in MSI CRC
CT should only be given for stage II MMS tumors if a high risk factor such as T4 local extension is present
MSI CRC shows a good response to irinotecan if BAX expression has been lost