By studying changes in tumor tissue from colon cancer patients whose cancers had not spread to distant organs, researchers were able to isolate a gene mutation that led to a poor outcome.
Stage I through III colon cancer patients whose tumors had a mutation in the PIK3CA gene were more likely to die of colon cancer that patients with normal or wild-type PIK3CA. About 1 in 5 patients had that mutation in tumor tissue.
After adjusting for other variables that affect death from colon cancer, patients with a PIK3CA mutation were more than twice as likely to die from colon cancer. This was especially true in KRAS wild-type tumors where a PIK3CA mutation increased risk of death almost four times. However, in KRAS mutated tumors, the presence of PIK3CA made little difference in cancer-specific survival.
Five years after surgery, 9 out of 10 patients whose tumors didn’t have PIK3CA mutations had not died of colon cancer compared to a little more than 8 out of 10 (84 percent) with mutated PIK3CA.
The study included 450 patients drawn from two large groups of both men and women who have been followed for many years. Women in the Nurse’s Health Study have been followed since 1976 with questionnaires every two years. Men from the Health Professionals Follow-up Study completed the biennial questionnaires since 1986.
Tumors were analyzed for a number of genetic changes including KRAS, BRAF, p53, MSI, CIMP, and LINE-1 methylation. The research team also recorded the age, sex, and body mass index of each patient, along with the year the cancer was diagnosis and its stage, location, and grade.
They found PIK3CA mutations in 18 percent of the tumors. PIK3CA mutations were more likely to be found along with KRAS mutations, but less likely to show expression of p53. There was no connection between PIK3CA and any clinical features of the cancers.
PIK3CA mutations activate a pathway in cancer cells that leads to cell division, cell survival, invasion of other tissues, and the development of new blood cells. Studies in colon cancer cells have found drugs that block PIK3 also have anti-tumor activity.
Shugi Ogino and colleagues at Dana Farber Cancer Institute in Boston concluded,
Among patients who undergo a curative resection of colon cancer, PIK3CA mutation is associated with shorter cancer-specific survival. The adverse effect of PIK3CA mutation may be potentially limited to patients with KRAS wild-type tumors.
SOURCE: Ogino et al., Journal of Clinical Oncology, Volume 27, Number 9, March 20, 2009.