VEGF expression may help explain RCC agressiveness

June 1, 2005

San Antonio--A new study examining the expression of the vascular endothelial growth factor (VEGF) family of proteins in kidney cancer has yielded several important findings, including the identification of different expression profiles of VEGF proteins in clear cell and papillary type renal cell carcinoma.

San Antonio-A new study examining the expression of the vascular endothelial growth factor (VEGF) family of proteins in kidney cancer has yielded several important findings, including the identification of different expression profiles of VEGF proteins in clear cell and papillary type renal cell carcinoma.

According to the UCLA researchers who carried out the study, VEGF proteins are signals that recruit new blood vessels that feed the growth kidney tumors.

"Our goal was to quantify the expression of these proteins and receptors in different types of renal cell carcinoma," said lead author John Leppert, MD, a UCLA urology resident working with Arie Belldegrun, MD, Robert Figlin, MD, and colleagues. "These differences might help explain why certain types of kidney cancers are more aggressive and spread more easily.

The researchers created an array of more than 380 kidney tumors from patients who underwent nephrectomies at UCLA. They then placed a small portion of each tumor onto a slide and used antibodies to stain the tissues to examine how much protein was present and where the protein was located.

They identified protein expression of the VEGF receptors on clear cell and papillary tumor epithelia.

Targeted therapies "There are currently several drugs that show promise in treating kidney cancer that target these very receptors," Dr. Leppert said. "Previously, it was thought that these receptors were located only on the blood vessels surrounding the tumor. We were able to locate these receptors to those blood vessels as well as to the cancer cells, themselves."

The researchers demonstrated that most of the 380 kidney tumors that they analyzed had high levels of these proteins and receptors.

"This may explain why drugs targeting these proteins appear to be effective in clinical trials," Dr. Leppert said.

They also identified different expression profiles of the proteins in clear cell and papillary type renal cell carcinoma.

"We were surprised to find that papillary type renal cell carcinoma also expresses high levels of these proteins," he said. "This suggests that patients with papillary tumors should also be included in clinical trials of these new targeted therapies. Ultimately, this information will help us choose which patients should receive these promising new drug therapies."

The data suggest that the VEGF family of proteins is an important signal for angiogenesis and that it is possible to refine treatment of patients with kidney cancer and optimize patient response rates by only giving these drug therapies to patients who are likely to receive benefit.

According to Dr. Leppert, surgery remains the primary treatment for localized kidney cancer and an important treatment option for patients with metastatic disease.

"By analyzing the tumor after it has been removed, we hope to be able to customize a unique treatment for each patient," he said. "We hope to block the proteins and receptors that signal the creation and recruitment of new blood vessels to the tumor. Our data suggests that both clear cell and papillary type renal cell carcinoma should be included in the clinical trials of these drugs."

These findings help urologists and researchers better understand the expression of these proteins in the different types of kidney cancer.

"We are just beginning to understand the role of the VEGF family in kidney cancer. We are optimistic that drug therapies that target these proteins will become important tools for the urologist in treating both clear cell and papillary type renal cell carcinoma," Dr. Leppert said.

"Future research will hopefully confirm our ability to predict the patients that are likely to respond to these drug therapies based on the expression profiles of VEGF proteins in their tumors."