UMMS PATHOLOGIST IDENTIFIES NOVEL BIOMARKER THAT CAN EFFECTIVELY PREDICT CANCER SPREAD
Findings published in The Lancet Oncology have immediate implications for diagnosis and treatment to improve outcomes of kidney cancer
June 14, 2006
WORCESTER, Mass.-Tumor metastasis, or the spread of cancerous cells from an original site to one or more sites elsewhere in the body, has often fatal consequences for cancer patients. Early detection and treatment of patients with the high potential to develop metastasis is crucial to improve cancer patient survival. Now, researchers at the University of Massachusetts Medical School and UMass Memorial Medical Center have identified the protein IMP3 as a novel biomarker that is a powerful new tool in the prediction of metastasis and the subsequent prognosis of patients with renal cell carcinoma-a discovery with near immediate implications for the treatment of this common cancer.
Accounting for more than 80 percent of malignant kidney tumors, renal cell carcinoma is the most common type of kidney cancer. In 2005, there were an estimated 36,160 new cases of kidney cancer in the United States and more than 12,000 people would die from this disease, with most fatalities caused by the metastasis, or spread, of the cancer from the kidney to other places in the body. Historically, it has been difficult to predict the potential of these tumors for mestastasis and consequently, treatment methods have been limited. In "Analysis of RNA-binding protein IMP3 to predict metastasis and prognosis of renal-cell carcinomas, a retrospective study," published June 14 in an advance online publication of The Lancet Oncology, University of Massachusetts Medical School Associate Professor of Pathology Zhong Jiang, MD, and collaborators from UMass Memorial Medical Center, Massachusetts General Hospital and City of Hope National Medical Center, demonstrate that IMP3 is an excellent independent prognostic marker that can be used at the time of initial diagnosis of RCC to identify a group of patients with a high potential to develop metastasis and who might benefit from early systemic therapy.
As noted, distant metastasis of renal cell carcinomas is the primary cause of death for affected patients and the metastatic potential of these tumors is often unpredictable. There is a great need for biomarkers that can accurately distinguish those tumors with a high probability of metastasis. In an effort to identify biomarkers for renal cell carcinoma, Dr. Jiang and colleagues chose to study IMP3, a protein that was already demonstrated to be highly expressed in primary tumors from other cancers, including lung and pancreatic cancers.
Examining the tissue samples and clinical information from 406 patients with primary renal cell carcinomas who underwent radical or partial kidney removal at three different medical centers, the scientists found that the expression of IMP3 was significantly increased in the metastatic renal cell carcinomas. They further demonstrated this elevated expression of IMP3 in primary renal cell carcinomas can predict tumor metastasis. Their data shows that the expression of IMP3 was significantly increased not only in metastastic renal cell carcinomas but most importantly also in patients with primary renal cell cancers who developed metastatic disease as compared with renal cell cancers without metastasis. Remarkably, Jiang and collaborators found that 80 percent of patients with IMP3 positivity in their localized renal cell carcinoma developed metastasis, whereas only 13 percent of patients without expression of IMP3 in their primary tumors developed metastases.
Because patients whose tumors express IMP3 have a high potential to develop metastasis, IMP3 provides a marker that can help identify those patients who might benefit from a different follow-up approach after partial or complete kidney removal. Surgical removal of primary renal cell carcinoma can be a curative treatment when the disease is localized; however because distant metastasis remains the primary cause of therapeutic failure, patients with metastatic disease are typically treated with systemic therapy. Systemic therapy, however, is associated with substantial toxicity and therefore is typically indicated only when a patient's cancer has spread. With this paper, the researchers propose that IMP3 can be used at initial diagnosis, which would be the optimal time for considering early systemic therapy for those patients whose cancer has a high likelihood of metastasizing.
"IMP3 testing is a simple, inexpensive and reliable assay that can be easily applied in routine clinical practice," explained Jiang. "If we can identify in those patients with early-stage disease the high potential to develop metastasis after surgery, we may be able to alter the course of therapy to improve outcomes and survival." Jiang and colleagues look forward to clinical studies to further evaluate the IMP3 testing in other cancers and the correlation to patient outcomes.
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Contact: Kelly Bishop