Biomarkers Predict Colorectal Cancer Survival

Two gene changes that occur in some colorectal cancers can forecast chances for good or poor survival.

Patients whose cancers had high microsatellite instability (MSI) had significantly better outcomes at every stage, but mutations in the KRAS gene predicted poorer survival.

Scientists in New York cancer centers assessed MSI and KRAS genetic mutations in 532 primary colorectal cancers removed during surgery.  Twelve percent of cancer had high levels of microsatellite instability (MSI), while 36 percent had mutations in the KRAS gene.

MSI was more common in early stages with very little MSI in cancers diagnosed at stage IV where cancer had spread beyond the colon:

• stage I– 15 percent
• stage II — 21 percent
• stage III — 10 percent
• stage IV — 2 percent

KRAS mutations were more evenly distributed across stages:

• stage I– 36 percent
• stage II — 34 percent
• stage III — 35 percent
• stage IV — 40 percent

Patients with MSI were much less likely to die of cancer within five years of their diagnosis.  More than 9 out of ten (92 percent) were alive five years later compared to 6 of 10 (59 percent) of those who didn’t show MSI.

KRAS was the opposite story.  Mutations in KRAS led to poorer five year survival with 55 percent alive compared to 68 percent of patients with normal KRAS (wild-type).

The researchers noted that there was a group of stage I and II patients who had a particularly poor chance of living 5 years.  Those patients didn’t have MSI but did have KRAS mutations.

Garrett M. Nash from the Department of Surgery at Memorial Sloan Kettering and his colleagues concluded,

MSI and KRAS mutation provide fundamental genetic signatures influencing tumor behavior across patient subsets and stages of tumor development.

SOURCE: Nash et al., Annals of Surgical Oncology, published online October 8, 2009.