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Prognostic Significance of Preoperative Molecular Serum Analysis in Renal Cancer

The James Buchanan Brady Urological Institute [M. L. G., C. F. E., B. J. T., S. H., D. S., M. P. S.] and Oncology Center [S. M. L.], The Johns Hopkins Medical Institutions, Baltimore, Maryland 21287-2101, and Department of Urology, Emory University School of Medicine, Atlanta, Georgia 30322 [F. F. M.]

Purpose: We evaluated the postoperative clinical course of patients with renal cancer identified preoperatively by microsatellite analysis to examine the correlation between microsatellite alterations and risk of disease recurrence and patient mortality 2 years after nephrectomy.

Experimental Design: A panel of 28 microsatellite markers was used previously to assess loss of heterozygosity and microsatellite instability in urine, serum, and tumor DNA of 30 patients with clinically organ-confined renal masses who underwent partial or radical nephrectomy. The clinical reports and imaging data in the medical records of patients with a minimum follow-up of 2 years were retrospectively reviewed to determine their postoperative course.

Results: Two-year follow-up was available for the 30 patients (100%) who entered the study. Mean age was 61.6 ± 12.9 years (range, 21–77 years). Tumor stage was associated with patient mortality (P = 0.03). Tumor grade was associated with mortality (P = 0.03) and disease recurrence (P < 0.01). The frequency of microsatellite alterations (loss of heterozygosity) found in the preoperative serum of patients with renal masses served as a prognostic indicator for disease recurrence (P < 0.01).

Conclusions: Analysis of microsatellite alterations found in preoperative blood samples is a promising method for the detection of renal cancer. The presence of frequent molecular changes in preoperative serum was associated with disease recurrence. These findings suggest a role for microsatellite analysis in future studies attempting to stratify patients with clinically organ-confined renal cancer into low- and high-risk prognostic groups. Larger prospective randomized trials are needed to validate the clinical utility of this observation.