Lara C. Pullen, PhD

October 09, 2012

October 9, 2012 (Chicago, Illinois) — Ki-67 expression is an independent predictor of renal cell carcinoma (RCC) progression and may serve as a valuable biomarker for patients with RCC, researchers reported at the American College of Surgeons (ACS) 98th Annual Clinical Congress.

Surgery is standard treatment for patients with RCC, yet approximately 1 in 5 patients will subsequently develop metastatic disease. Therefore, Kelvin Wong, MD, from the University of Wisconsin, Madison, and colleagues used tissue microarrays to look for protein biomarkers that predict disease progression and might identify patients who need further adjuvant treatment.

The authors searched an institutional database to identify patients with RCC who underwent radical or partial nephrectomy with no lymph node or distant metastasis at surgery. The database included 223 patients with a median follow-up of 60.5 months. Of those, 40 (18%) patients developed metastatic disease.

The investigators constructed a tissue microarray from patient tumor samples and used immunohistochemistry to measure expression of 6 proteins: C-reactive protein, NFκB, CA 9, HIF1a, HIF2a, and Ki-67.

According to the authors, immunohistochemistry represents a straightforward and relatively cheap way to measure protein expression with automated quantification of fluorescent antibody signal intensity.

"What the computer can do is really separate spatially the different layers for us," Dr. Wong explained. "You can remove a lot of the inter-observer variability [using this type of system]." He acknowledged, however, that "the technology software needs a human element to tell the program what to recognize."

Ki-67 Correlates With Progression

Tumor size, grade, stage, subtype, sarcomatoid features, venous thrombus, perinephric fat invasion, and increased Ki-67 expression correlated with progression in a univariate analysis.

In a multivariate analysis, tumor size, level of thrombus, and Ki-67 remained independent risk factors for RCC recurrence. Of all of the factors identified, Ki-67 overexpression was most predictive of recurrence (hazard ratio, 8.4 [95% confidence interval, 3.8 - 19.0]).

David R. Byrd, MD, from the Seattle Cancer Care Alliance in Washington moderated the session and noted that the data suggest "that Ki-67 is something that should be routinely collected." Currently, physicians do not routinely request the test.

An estimated 65,000 new diagnoses of kidney cancer are expected in the United States in 2012. Kidney cancer is the eighth most common cancer in men and the sixth most common cancer in women. It is often difficult to determine who will progress.

Although to date adjuvant therapy has no known benefit, there may be a benefit if it became possible to predict who is at highest risk for progression.

Dr. Wong and Dr. Byrd have disclosed no relevant financial relationships.

American College of Surgeons (ACS) 98th Annual Clinical Congress. Abstract NP2012-24333. Presented October 3, 2012.