Renal cell carcinoma--prognostic factors.
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Biomedical subjects
Publications and source records attributed to Fray F Marshall.
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In a previous large-scale gene expression profiling study of renal epithelial neoplasms, human beta-defensin-1 (DEFB1) was found to be significantly down-regulated in conventional clear cell (renal) carcinoma. We have now completed an expanded expression analysis of this gene. We performed immunohistochemical analysis for the DEFB1 protein in clinical specimens of both renal cell carcinoma and prostate cancer. In a subset of prostate cancers, we performed laser capture microdissection and RT-PCR to correlate mRNA levels with protein levels. Overall, 82% of prostate cancers exhibit either complete loss of protein expression or only minimal expression, whereas the adjacent benign epithelium retained expression in all cases. Similarly, 90% of renal cell carcinomas show cancer-specific loss of DEFB1 protein. In the prostate cancer subset analysis, mRNA levels correlate with protein levels. We have thus demonstrated the cancer-specific down-regulation of DEFB1 in a large sample of prostatic and renal carcinomas and validated one of the key findings of previous cancer gene profiling studies of prostatic and renal neoplasia.
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PURPOSE: We have previously reported that patients with advanced renal cell carcinoma and a normal platelet count of 400,000/mm. have a 64% increase in life expectancy compared with those with thrombocytosis. We determined whether thrombocytosis was predictive of death from renal cell carcinoma after radical nephrectomy was performed with curative intent for early stage disease. MATERIALS AND METHODS: We reviewed the records of 204 patients with renal cell carcinoma who underwent radical nephrectomy with curative intent between June 1993 and January 2000 at Emory University Hospital. Survival, pathological grade and stage were recorded from the Emory Winship Cancer Institute tumor registry. Platelet counts were recorded and any patient with at least 1 platelet count of greater than 400,000/mm. was classified with thrombocytosis. Those with a platelet count of 400,000/mm. were classified with a normal platelet count. RESULTS: There were 26 patients with thrombocytosis and 178 patients with persistently normal platelet counts. The overall and cancer specific death rate in the 26 patients with thrombocytosis was 50% and 42%, respectively. The overall mean time between nephrectomy and death was 12.1 months in this group. The overall and cancer specific death rate in the 178 patients with a normal platelet count was 15.2% and 7.3%, respectively. Mean time to death was 22.6 months in this group. Differences in the overall and cancer specific death rates were highly statistically significant as well as clinically significant. These differences remained significant after controlling for grade, stage and histological type of cancer. CONCLUSIONS: This study documents the association of thrombocytosis with decreased survival in patients with renal cell carcinoma. In those who undergo nephrectomy for early stage renal cell carcinoma with a perioperative platelet count of greater than 400,000/mm. the cancer specific death rate from renal cell carcinoma is greater than 5 times the rate in patients with a persistently normal platelet counts after radical nephrectomy. The platelet count appears to be a new and powerful independent prognosticator in patients with renal cell carcinoma who undergo radical nephrectomy for presumed localized disease.
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.
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