Researchers Show That Molecular Markers Predict Tumor Recurrence

The findings may also help identify stage II colon cancer patients who are more likely to benefit from adjuvant chemotherapy following surgery, says Georg Lurje M.D., research associate at the Keck School of Medicine of the University of Southern California (USC).

The study was presented Tuesday, June 5 at the 2007 annual meeting of the American Society of Clinical Oncology (ASCO) held at McCormick Place in Chicago.

For patients who undergo surgery for stage III colon cancer¬--in which the tumor has spread to the lymph nodes--additional chemotherapy is recommended to prevent tumor recurrence, Lurje says. While surgery alone is usually effective for treating stage II cancer, 20 to 30 percent of patients do develop tumor recurrence and die from the disease, he says.

"This study is the very first to demonstrate that genes in the angiogenesis pathway play a critical role in tumor relapse," says Heinz-Josef Lenz, M.D., professor of medicine at the Keck School and the 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."

Angiogenesis refers to the blood vessel formation that provides nutrients and oxygen to cancerous growths. Researchers analyzed blood specimens that were obtained at USC medical facilities 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 patients 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 study shows.

The results also show 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, Lurje says.

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, he notes.

"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," Lurje explains. "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."

Funding for this study comes from the Dhount Foundation.

Reference: Georg Lurje, Anne M. Schultheis, Andrew E. Hendifar, Shahryar Ashouri, Wu Zhang, Michael A. Gordon, Fumio Nagashima, Hueng-M. Chang and Heinz-Josef Lenz, "Angiogenesis gene polymorphisms predict tumor recurrence in stage II and III colon cancer."