Variations in two genes, one for vascular endothelial growth factor (VEGF) and one for the receptor VEGFR-2, may be useful markers to help predict risk of recurrence for patients with stage II or III colon cancer and help identify stage II patients most likely to benefit from postoperative chemotherapy, according to a presentation at the annual meeting of the American Society of Clinical Oncology.

Predictive markers may make a significant difference in care of patients with stage II disease: Roughly 20 to 30 percent of patients develop tumor recurrence and die from the disease.

“This study is the very first to demonstrate that genes in the angiogenesis pathway play a critical role in tumor relapse,” said Heinz-Josef Lenz, MD, professor of medicine at the Keck School of Medicine, University of Southern California, and principal investigator on the study. “These molecular markers not only help us to identify patients who are at high risk, but they may be critical to selecting the most efficient therapy.”

In the current study, researchers analyzed blood specimens obtained between 1999 and 2007, testing whether a specific pattern of polymorphisms in 33 genes involved in cancer progression predicted tumor recurrence. Of the 197 patients who participated, 72 had stage II and 125 had stage III colon cancer.

Researchers identified the vascular endothelial growth factor protein (VEGF) and its receptor VEGFR-2 as one of the most important activators of tumor angiogenesis. Patients with polymorphisms in the EGFR and VEGFR genes had a higher likelihood of tumor recurrence.

The results also showed that patients with stage II colorectal cancer seem to have a different molecular profile for tumor recurrence. However, further trials are needed to validate the preliminary data, Georg Lurje, MD, the presenter, said.

The findings may help oncologists target patients who will benefit the most from adjuvant chemotherapy. The treatment remains controversial for stage II patients because the majority do not have tumor relapse.

Lurje explained, “That means that 70 to 80 percent of stage II patients would be treated with chemotherapy without benefit, but with an increase of potential side effects like toxicity. However, 20 to 30 percent of stage II patients do recur and the goal is to identify those patients with higher risk for tumor recurrence and treat only those patients.”