Genes Correlate with RCC Recurrence Risk
CHICAGO—Researchers at Cleveland Clinic, in collaboration with Genomic Health, Inc. and Pfizer, say they have demonstrated for the first time a strong correlation between gene expression and risk of disease recurrence in patients with early-stage renal cell carcinoma (RCC).
The finding, presented at the American Society of Clinical Oncology annual meeting, could aid in identifying high-risk patients beyond the conventional clinical and pathologic parameters. Further, these data could serve as a basis to identify early-stage RCC patients who could benefit most from treatment.
“Many early-stage renal cell carcinoma patients experience a recurrence of their cancer, yet there is currently no accurate means to identify the most aggressive cancers in advance,” said principal study investigator Brian I. Rini, MD, Associate Professor of Medicine at the Cleveland Clinic Taussig Cancer Institute in Ohio. “The strong correlation between gene expression and recurrence risk demonstrated in this study could help select the appropriate renal cell carcinoma patients for future drug development trials and potentially identify patients most likely to benefit from adjuvant therapy following surgery.”
Dr. Rini and his colleagues identified patients with stage I, II, and III clear cell RCC who underwent nephrectomy at the Cleveland Clinic between 1985 and 2003 with archived paraffin-embedded nephrectomy samples. They excluded patients with inherited RCC and those who received neoadjuvant systemic therapy or had fewer than six months of follow-up. Investigators extracted RNA from paraffin tumor sections and quantified RNA expression for 732 genes (including reference genes). The primary endpoint for this investigation was recurrence-free interval (RFI), defined as the time from nephrectomy to first recurrence or death due to RCC.
A total of 931 patients with complete clinical and pathology data and tissue blocks were evaluable. Of these patients, 63% were male and the median age was 61 years. A total of 68% has stage I disease, 10% had stage II disease, and 22% had stage III disease. The study group had a median follow-up of 5.6 years.
The clinical and pathologic covariates that significantly associated with RFI were microscopic necrosis, Fuhrman grade, stage, tumor size, and lymph node involvement. A total of 448 genes were significantly associated with RFI and 300 genes were significantly associated with four of the five covariates. After adjusting for significant clinical/pathologic covariates and false discovery, 16 genes remained significantly and strongly associated with RFI. Dr. Rini emphasized that these data are preliminary and represent only the first gene discovery step requiring further validation and separate analyses to develop a gene test predictive of benefit to targeted therapy.