Familiar biomarker may predict RCC metastasis

Worcester, MA-An off-the-shelf test for an already-identified biomarker may emerge as a quick, simple, and affordable screen for aggressive renal cell carcinoma. Clinicians may soon be able to identify their highest-risk kidney cancer patients and begin aggressive treatment earlier in the course of their disease.

"Right now, after nephrectomy, there is no further treatment unless you have already found metastases," said Zhong Jiang, MD, associate professor of pathology at the University of Massachusetts Medical School, Worcester. "I think the discovery of this biomarker is going to change the way urologists and oncologists practice."

"Our study was retrospective," Dr. Jiang said. "We need to have a prospective trial to be sure we can use this marker in clinical practice."

Metastatic tumors test positive

Dr. Jiang's group examined tumor samples from 501 primary and metastatic RCC patients at UMMS, Massachusetts General Hospital in Boston, and City of Hope National Medical Center in Los Angeles. All of the patients were admitted between 1989 and 2003 and had adequate clinical data for follow-up study. A subgroup of 371 patients with localized primary tumors was further studied to see if their cancer spread. Median follow-up time was 63 months.

About 20% of primary RCC tumors were IMP3 positive, Dr. Jiang reported. Approximately 60% of the metastatic tumors tested positive for the marker. The marker was also associated with higher tumor grade and with large tumor size.

The median 5-year metastasis-free survival for IMP3-negative patients was 89% versus 33% for patients with IMP3 expressed in their primary tumor. The patients with IMP3-positive primary tumors were almost six times more likely to develop metastasis after adjustment for tumor size, stage, grade, and other clinical prognostic factors.

Overall 5-year survival was 82% for IMP3-negative tumors and 27% for IMP3-positive tumors. The patients with IMP3-positive primary tumors were four times more likely to die than those with IMP3-negative tumors after adjustment for clinical factors important to patient survival, such as age and tumor stage.

Differences were even more dramatic for later-stage patients. In patients with stage III disease, almost all of the IMP3-positive patients developed metastases and died, even after their primary kidney tumors were removed.

"All of these positive markers point to metastasis," Dr. Jiang said. "If patients have a positive marker, they should probably begin systemic treatment to delay metastasis."

No apparent pattern

There was no apparent pattern to the site of metastases in the study, Dr. Jiang said, and IMP3 is not found in non-cancerous tissues. But that should not be a barrier to improving treatment.

The standard of care for RCC is nephrectomy, so tumor tissue is available for analysis in nearly all patients. If the tumor is IMP3-negative, the patient has a good prognosis. If the tumor is IMP3-positive, systemic therapy can be begin immediately rather than waiting for evidence of metastasis. The earlier treatment begins, Dr. Jiang noted, the more successful it is likely to be.

"The staining of this tissue is quite routine," Dr. Jiang said. "This marker is quite easy to use and quite cheap. Materials are easily available. I would be surprised if some urologists are not already using this screen."