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Clear-cell Renal Cell Carcinoma (clear-cell + renal_cell_carcinoma)
Selected AbstractsGene signatures of pulmonary metastases of renal cell carcinoma reflect the disease-free interval and the number of metastases per patientINTERNATIONAL JOURNAL OF CANCER, Issue 2 2009Daniela Wuttig Abstract Our understanding of metastatic spread is limited and molecular mechanisms causing particular characteristics of metastasis are largely unknown. Herein, transcriptome-wide expression profiles of a unique cohort of 20 laser-resected pulmonary metastases (Mets) of 18 patients with clear-cell renal cell carcinoma (RCC) were analyzed to identify expression patterns associated with two important prognostic factors in RCC: the disease-free interval (DFI) after nephrectomy and the number of Mets per patient. Differentially expressed genes were identified by comparing early (DFI , 9 months) and late (DFI , 5 years) Mets, and Mets derived from patients with few (,8) and multiple (,16) Mets. Early and late Mets could be separated by the expression of genes involved in metastasis-associated processes, such as angiogenesis, cell migration and adhesion (e.g., PECAM1, KDR). Samples from patients with multiple Mets showed an elevated expression of genes associated with cell division and cell cycle (e.g., PBK, BIRC5, PTTG1) which indicates that a high number of Mets might result from an increased growth potential. Minimal sets of genes for the prediction of the DFI and the number of Mets per patient were identified. Microarray results were confirmed by quantitative PCR by including nine further pulmonary Mets of RCC. In summary, we showed that subgroups of Mets are distinguishable based on their expression profiles, which reflect the DFI and the number of Mets of a patient. To what extent the identified molecular factors contribute to the development of these characteristics of metastatic spread needs to be analyzed in further studies. © 2009 UICC [source] Carbonic anhydrase IX and pathological features as predictors of outcome in patients with metastatic clear-cell renal cell carcinoma receiving vascular endothelial growth factor-targeted therapyBJU INTERNATIONAL, Issue 6 2010Toni K. Choueiri Study Type , Prognosis (retrospective cohort) Level of Evidence 2b OBJECTIVE To investigate the utility of tumour carbonic anhydrase IX (CAIX) expression and histological features for predicting the outcome in patients with metastatic clear-cell renal cell carcinoma (mRCC) treated with vascular endothelial growth factor (VEGF)-targeted therapy. PATIENTS AND METHODS We identified 118 patients with mRCC initiating first-line VEGF-targeted therapy, including 94 with clinical and histological data, and available tissue. The primary endpoint was to detect an interaction between sorafenib vs sunitinib treatment and CAIX status on tumour shrinkage. Other treatment outcomes were also assessed. RESULTS There was heterogeneity in tumour responsiveness to sunitinib or sorafenib according to CAIX status; the mean shrinkage was ,17% vs ,25% for sunitinib-treated patients with high vs low tumour CAIX expression, compared to ,13% vs +9% for sorafenib-treated patients (P interaction, 0.05). A higher tumour clear-cell component was independently associated with greater tumour shrinkage (P= 0.02), response (P= 0.02) and treatment duration (P= 0.02). CONCLUSIONS Although CAIX expression had no prognostic value in patients with clear-cell mRCC treated with VEGF-targeted therapy, it might be a predictive biomarker for response to sorafenib treatment. Patients with a higher clear-cell component in their tumours are likely to have a superior clinical benefit from VEGF-targeted therapy. [source] Obesity is associated with a higher risk of clear-cell renal cell carcinoma than with other histologiesBJU INTERNATIONAL, Issue 1 2010William T. Lowrance Study Type , Prognosis (cohort) Level of Evidence 2a OBJECTIVE To investigate the association between body mass index (BMI) and histology of renal cell carcinoma (RCC) in a contemporary cohort, as obesity is increasingly prevalent in the USA and might be contributing to the increasing incidence of RCC, but little is known about the relationship of obesity with the different histological subtypes of RCC. PATIENTS AND METHODS From January 2000 to December 2007 we identified 1640 patients with renal cortical tumours undergoing surgical extirpation at our institution, and who had their BMI recorded. Multivariable logistic regression models were used to test the association of BMI with RCC histology. RESULTS The median (interquartile range) BMI was 28 (25,32) kg/m2 and 38% of patients were classified as obese (BMI >30 kg/m2). After adjusting for tumour size, age, gender, American Society of Anesthesiologists score, estimated glomerular filtration rate, hypertension, diabetes mellitus and smoking, the BMI was significantly associated with clear-cell histology; the odds ratios were 1.04 for each unit of BMI (95% confidence interval, CI, 1.02,1.06; P < 0.001) and 1.48 when comparing obese vs non-obese patients (95% CI 1.19,1.84; P < 0.001). In the subgroup of patients with RCC (excluding benign renal cortical tumours), BMI was still an independent predictor of clear-cell histology (odds ratio 1.04, 95% CI 1.02,1.06, P = 0.001). CONCLUSIONS These results suggest that BMI is an independent predictor of clear-cell histology in patients with a renal cortical tumour. While the aetiology of this phenomenon requires further study, these findings might have implications in determining a patient's risk of harbouring a clear-cell RCC and in subsequent treatment recommendations. [source] Mononuclear cell infiltration in clear-cell renal cell carcinoma independently predicts patient survivalCANCER, Issue 1 2006W. Scott Webster MD Abstract BACKGROUND The impact of mononuclear cell infiltration on renal cell carcinoma (RCC) biology has been controversial, previously reported to be associated with either a favorable or unfavorable prognosis. The objective of the current study was to evaluate associations between mononuclear cell infiltration in routinely prepared paraffin-embedded specimens with survival in patients with clear-cell RCC. METHODS A total of 306 patients were identified treated with nephrectomy for clear-cell RCC between 1990 and 1994. A single urologic pathologist, blinded to patient outcome, reviewed the specimens and quantified the extent of mononuclear cell infiltration as absent, focal, moderate, or marked. Cancer-specific survival was estimated using the Kaplan,Meier method. Associations of mononuclear cell infiltration with death from RCC were assessed using Cox proportional hazards regression models. RESULTS At last follow-up, 173 of the 306 patients studied had died, including 96 patients who died from RCC. Mononuclear cell infiltration was absent in 165 (54%), focal in 70 (23%), moderate in 53 (17%), and marked in 18 (6%). Univariately, patients with specimens that had mononuclear cell infiltration were over 2 times more likely to die from RCC compared with patients whose specimens exhibited no mononuclear cell infiltration (risk ratio, 2.63; P<.001). After adjusting for the Mayo Clinic SSIGN (stage, size, grade, and necrosis) score, patients with specimens that had mononuclear cell infiltration exhibited a significantly increased likelihood of dying from RCC compared with patients whose specimens had no mononuclear cell infiltration (risk ratio, 1.61; P = .028). CONCLUSIONS Mononuclear cell infiltration is associated with death from RCC even after multivariate adjustment. Routine documentation of mononuclear cell infiltration is recommended during the pathologic assessment of RCC. Cancer 2006. © 2006 American Cancer Society. [source] | ||||||||||