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Clear Cell RCC (clear + cell_rcc)
Selected AbstractsCharacterization of a 3;6 translocation associated with renal cell carcinomaGENES, CHROMOSOMES AND CANCER, Issue 4 2007Rebecca E. Foster The most frequent cause of familial clear cell renal cell carcinoma (RCC) is von Hippel,Lindau disease and the VHL tumor suppressor gene (TSG) is inactivated in most sporadic clear cell RCC. Although there is relatively little information on the mechanisms of tumorigenesis of clear cell RCC without VHL inactivation, a subset of familial cases harbors a balanced constitutional chromosome 3 translocation. To date nine different chromosome 3 translocations have been associated with familial or multicentric clear cell RCC; and in three cases chromosome 6 was also involved. To identify candidate genes for renal tumorigenesis we characterized a constitutional translocation, t(3;6)(q22;q16.1) associated with multicentric RCC without evidence of VHL target gene dysregulation. Analysis of breakpoint sequences revealed a 1.3-kb deletion on chromosome 6 within the intron of a 2 exon predicted gene (NT_007299.434). However, RT-PCR analysis failed to detect the expression of this gene in lymphoblast, fibroblast, or kidney tumor cell lines. No known genes were disrupted by the translocation breakpoints but several candidate TSGs (e.g., EPHB1, EPHA7, PPP2R3A RNF184, and STAG1) map within close proximity to the breakpoints. © 2007 Wiley-Liss, Inc. [source] Renal cell carcinoma marker reliably discriminates central nervous system haemangioblastoma from brain metastases of renal cell carcinomaHISTOPATHOLOGY, Issue 6 2008B Ingold Aims:, The distinction between central nervous system (CNS) metastases of clear cell renal cell carcinoma (RCC) and CNS haemangioblastoma still poses a challenge to the pathologist. Since both entities occur in von Hippel,Lindau disease, this aggravates the issue. The antibody renal cell carcinoma marker (RCC-ma) has been suggested to identify primary RCCs specifically, but its value for diagnosing metastases of RCC is controversial. The aim was to assess two distinct clones of the RCC-ma for their potential to: (i) identify primary RCCs and (ii) differentiate between CNS metastases of clear cell RCC and CNS haemangioblastomas. Methods and results:, Using tissue microarrays, 77% (n = 363; PN-15) and 66% (n = 355; 66.4C2) of clear cell RCCs, and 93% (PN-15) and 74% (66.4C2) of papillary RCCs (n = 46) were immunopositive for RCC-ma, whereas none of the investigated chromophobe RCCs (n = 22) or any of the oncocytomas (n = 15) showed immunoreactivity. Importantly, 50.9% of CNS metastases of clear cell RCCs (n = 55) exhibited RCC-ma expression, whereas all CNS haemangioblastomas (71) were negative. Conclusions:, Both RCC-ma clones, despite some variation in their sensitivity to detect clear cell and papillary RCCs, are of value in differentiating subtypes of primary RCC and are excellent markers for discriminating clear cell lesions in the brain. [source] The diagnostic utility of MOC31, BerEP4, RCC marker and CD10 in the classification of renal cell carcinoma and renal oncocytoma: an immunohistochemical analysis of 328 casesHISTOPATHOLOGY, Issue 5 2004C-C Pan Aims:, To demonstrate the diagnostic utility of MOC31, BerEP4, renal cell carcinoma marker (RCC Ma) and CD10 in the classification of RCC and renal oncocytoma, based upon a comprehensive immunohistochemical analysis. Methods and results:, Immunohistochemistry was performed on 328 samples consisting of 256 clear cell/conventional, 27 papillary, 28 chromophobe, five collecting duct, five unclassified RCCs and seven renal oncocytomas using antibodies MOC31, BerEP4 and antibodies against cytokeratins (KL-1, CAM5.2, 34,E12, cytokeratin 7), RCC Ma, epithelial membrane antigen, E-cadherin, CD10, CD15 and vimentin. Multivariate analysis showed that MOC31, BerEP4, RCC Ma and CD10 have discriminatory value. MOC31 and BerEP4 chiefly labelled distal tubules of normal kidney while RCC Ma and CD10 labelled the proximal tubules. Twenty-three chromophobe RCCs (82%) were reactive for MOC31, while only four clear cell RCCs and three papillary RCCs were positive for this marker. Clear cell RCCs were characterized by a high positive rate for CD10 (82%) and a low positive rate for BerEP4 (27%). Papillary RCCs frequently coexpressed RCC Ma and BerEP4 (51%). All renal oncocytomas were negative for MOC31 and CD10. Conclusions:, MOC31 has diagnostic merit in discerning chromophobe RCC. The CD10+/BerEP4, profile and RCC Ma+/BerEP4+ profile achieve moderate sensitivity and good specificity for clear cell RCC and papillary RCC, respectively. The non-reactivity for both MOC31 and CD10 is helpful in distinguishing renal oncocytoma from RCC. When properly selected, antibodies have immunohistochemical diagnostic utility for the classification of renal cortical epithelial tumours. [source] DOK4/IRS-5 expression is altered in clear cell renal cell carcinomaINTERNATIONAL JOURNAL OF CANCER, Issue 5 2007Nael Al-sarraf Abstract The insulin-receptor substrate family plays important roles in cellular growth, signaling, and survival. We have previously shown the dysregulation of the IGF-axis in clear cell renal cell carcinoma. In this manuscript, we examine the expression of the insulin receptor substrate family in clear cell RCC, and demonstrate that the expression of 2 members of this family are significantly altered in tumors. The most striking finding is that expression of the new IRS family member IRS-5 is significantly upregulated in 90% of examined clear cell RCCs. Studies on this gene has shown that it is regulated through chromatin remodeling in kidney cells. © 2007 Wiley-Liss, Inc. [source] Chromophobe renal cell carcinoma: Clinical, pathological and molecular biological aspectsPATHOLOGY INTERNATIONAL, Issue 11 2000Yoji Nagashima Chromophobe renal cell carcinoma (RCC), a newly established subtype of renal neoplasm, is composed of tumor cells with characteristically cloudy, weakly eosinophilic and reticular cytoplasm. The tumor should be distinguished from the common clear cell RCC, because of the unique clinicopathological and molecular biological features. The tumor does not show gender bias. Patient ages are similar to those of clear cell RCC, but might occur in the 20- to 40-year-old age group. Grossly, the tumor tends to be beige in color, which is different from the yellowish color of common RCC. Electron microscopy and immunohistochemistry indicate the intercalated cell of the collecting duct as the cellular origin. Cytogenetic study shows non-random multiple chromosome loss, with mitochondrial DNA rearrangement. Alteration of the von Hippel,Lindau (VHL) gene, a cancer suppressor gene relating with clear cell RCC, has not yet been observed. In order to adopt the most appropriate treatment, including gene therapy, recognition and correct pathological diagnosis of chromophobe RCC are extremely important. [source] The prognostic value of peritumoral regulatory T cells and its correlation with intratumoral cyclooxygenase-2 expression in clear cell renal cell carcinomaBJU INTERNATIONAL, Issue 3 2009Jin F. Li OBJECTIVE To investigate the prognostic value of regulatory T cells (Tregs) and its correlation with cyclooxygenase-2 (COX-2) expression in clear cell renal cell carcinoma (RCC). PATIENTS AND METHODS CD4+, Foxp3+ tumour-infiltrating lymphocytes and tumour COX-2 expression were assessed by immunohistochemistry in tissue microarrays containing RCC from 125 patients. Prognostic effects of low and high expression were evaluated by Cox regression and Kaplan,Meier analysis using the median values as thresholds. The expression of Tregs and COX-2 were compared with the clinicopathological variables. In addition, Tregs and its correlation with COX-2 expression was also analysed. RESULTS Peritumoral Tregs were positively correlated with intratumoral COX-2 expression (Spearman rank correlation 0.336, P < 0.001). Peritumoral Tregs were associated with TNM stage (P = 0.001) and tumour size (P = 0.002), while intratumoral COX-2 expression was associated with TNM stage (P = 0.018) and grade (P = 0.013). Using multivariate analysis, increased peritumoral Tregs, higher TNM stage (III + IV), larger tumour size (,7 cm) and higher nuclear grade (III + IV) were independent predictors for significantly shorter overall survival and disease-free survival. CONCLUSIONS Increased peritumoral Tregs are associated with worse prognosis in clear cell RCC. The high intratumoral COX-2 expression may be the underlying reason for the aberrant gathering of Tregs. These results suggest that clinical application of COX-2 inhibitors may benefit those patients with higher intratumoral COX-2 immunostaining by reducing the transformation of Tregs in RCC. [source] Enucleation of renal cell carcinoma with ablation of the tumour baseBJU INTERNATIONAL, Issue 6 2008Alexander Kutikov OBJECTIVE To retrospectively assess the effectiveness of cancer control with enucleation of renal cell carcinoma (RCC), which is surgically expedient, allows preservation of maximal renal parenchyma, and makes intraoperative renal ischaemia unnecessary, by two surgeons routinely enucleating renal tumours and ablating the tumour bed with argon beam and the Nd-YAG laser. PATIENTS AND METHODS Between 1996 and 2006 at our institution, 97 patients had RCC enucleated, with ablation of the tumour base. Patients with lesions other than RCC and those with von Hippel-Lindau disease or Birt-Hogg-Dube syndrome were excluded from the study. The mean follow-up was 24.9 months. Patients were evaluated for RCC recurrence with cross-sectional imaging at least every 6 months for the first 2 years and then annually thereafter. RESULTS The mean (median, range) tumour size was 2.8 (2.5, 0.8,7.0) cm. Of the 97 patients only one had disease progression after a mean follow-up of 24.9 months. This patient presented with a solitary grade 2 clear cell RCC and had a local recurrence 30 months after original surgery. CONCLUSIONS The present series and other available clinical data suggest that enucleation with cavity ablation is an oncologically sound approach that is simple, versatile and obviates the need for renal ischaemia. [source] Prognostic significance of erythropoietin expression in human renal cell carcinomaBJU INTERNATIONAL, Issue 2 2007Agniezka Michael OBJECTIVES To investigate, in a retrospective study, the expression of erythropoietin (Epo) in human renal cell carcinoma (RCC) and its correlation with overall survival, as Epo (an haematopoietic cytokine that regulates the production of red blood cells), with its receptor, was recently localized in non-haematopoietic tissues, e.g. liver, uterus, central nervous system, vascular endothelial cells and solid tumours. PATIENTS AND METHODS We used data from 113 patients who had radical nephrectomy for RCC between 1990 and 2000, taking sections from formalin-fixed and paraffin wax-embedded tissue blocks. The association between Epo staining and the patients' characteristics was assessed by either chi-squared tests (for categorical variables) or two-sample independent t -tests (for continuous variables). RESULTS Tissue from 37 patients (33%) was positive for cytoplasmic Epo expression; 76 (67%) samples were negative. Univariate hazard ratio analysis confirmed that those with positive Epo staining were more than twice as likely to die as those with negative staining (hazard ratio 2.34, 95% confidence interval 1.27,4.3). CONCLUSION This study shows that the expression of Epo in RCC is adversely associated with overall survival. This is the first report of such an association, and might be explained by the loss of Von Hippel-Lindau protein function in clear cell RCC. The expression of Epo might have potential use in clinical trials when stratifying high-risk patients for adjuvant therapy after nephrectomy. [source] DCC protein expression in clear cell renal cell carcinomaBJU INTERNATIONAL, Issue 6 2004Y. Dekel OBJECTIVES To investigate whether the expression of protein from the ,deleted in colorectal cancer' (DCC) gene, which predicts a poor outcome for patients with colorectal carcinoma, can also serve as a prognostic factor in renal cell carcinoma (RCC). PATIENTS AND METHODS The expression of DCC was evaluated immunohistochemically in 94 paraffin-embedded tumour samples from patients with stage T1, T2, and T3 clear cell RCC. The mean follow-up was 52.3 months. The endpoints of the study were recurrence of disease and death from disease. RESULTS The under-expression of DCC protein was detected in 63% of patients who died from the disease and in 36% with no evidence of disease. DCC protein under-expression was detected in all patients with T1 tumours who died from the disease, in half the T2 tumours and in two-thirds of T3 tumours. CONCLUSION DCC protein under-expression correlated with more aggressive tumour behaviour and a greater risk of death from RCC. However, a larger cohort of patients should be assessed before drawing definitive conclusions. [source] Costimulatory molecule B7-H1 in primary and metastatic clear cell renal cell carcinomaCANCER, Issue 10 2005R. Houston Thompson M.D. Abstract BACKGROUND Cancer cell expression of costimulatory molecule B7-H1 has been implicated as a potent inhibitor of T-cell,mediated antitumoral immunity. The authors recently reported that B7-H1 is aberrantly expressed in primary renal cell carcinoma (RCC). Blockade of B7-H1, as demonstrated in several murine cancer models, now represents a promising therapeutic target in RCC. However, the potential expression of B7-H1 in metastatic RCC has not been investigated. In the current study, the authors updated their primary RCC results with additional follow-up and investigated the potential role of B7-H1 in metastatic RCC. METHODS Between 2000 and 2004, 196 patients underwent nephrectomy and 26 patients had resection of RCC metastases for clear cell RCC. Immunohistochemical analysis was performed on tumor cryosections using a B7-H1 monoclonal antibody (clone 5H1). A urologic pathologist quantified the percentage of B7-H1,positive tumor cells and lymphocytes. RESULTS Variable levels of B7-H1 were expressed on primary RCC tumor cells (n = 130 [66.3%]) and primary tumor-infiltrating lymphocytes (n = 115 [58.7%]). Patients with high expression of B7-H1 on primary tumor cells and/or lymphocytes were significantly more likely to die of RCC compared with patients with low B7-H1 expression (risk ratio [RR] = 4.17; 95% confidence interval [95% CI], 1.97,8.84; P < 0.001) and this risk persisted in multivariate analysis after adjusting for the Mayo Clinic stage, size, grade, and necrosis score (RR = 2.63; 96% CI, 1.23,5.64; P = 0.013). Of the 26 metastatic specimens, cancer cell and lymphocyte B7-H1 expression were demonstrated in 17 (65.4%) and 18 (69.2%) specimens, respectively. In total, 14 (54.3%) metastatic specimens had high aggregate B7-H1 levels compared with 44.4% in primary RCC specimens. CONCLUSIONS Patients with RCC with high B7-H1 expression were significantly more likely to die even after multivariate analysis. The authors also demonstrated that a high percentage of RCC metastases similarly harbored B7-H1. The authors surmised that B7-H1 blockade may augment current immunotherapy, including patients treated for metastases after cytoreductive nephrectomy. Cancer 2005. © 2005 American Cancer Society. [source] Low expression of p27Kip1 is associated with tumor size and poor prognosis in patients with renal cell carcinoma,CANCER, Issue 4 2002Toshiro Migita M.D. Abstract BACKGROUND Proliferative activity in tumors depends on regulation of the cell cycle. p27Kip1 (p27) plays a pivotal role as a negative regulator of the cell cycle. A decrease in p27 expression has been reported in many kinds of tumors, but little is known regarding p27 in patients with renal cell carcinoma (RCC). METHODS Expression of p27 and the related cyclins (cyclin A, cyclin E, and cyclin D1) was examined immunohistochemically in 67 patients with of clear cell RCC. The Ki-67 labeling index (MIB-1 LI) and clinicopathologic parameters related to a poor prognosis also were analyzed. To determine their prognostic significance, univariate and multivariate survival analyses were performed. RESULTS In tumors, there was considerable immunoreactivity for cyclin A, cyclin D1, and MIB-1, and the mean values for each were 1.08%, 16.1%, and 1.5%, respectively. Cyclin E expression was rare. The expression of p27 was correlated strongly with the expression of cyclin A (correlation coefficient, 0.432; P < 0.0004) and cyclin D1 (correlation coefficient, 0.476; P < 0.0004). Also, an inverse correlation was present between p27 expression and tumor size (P = 0.0377). In univariate analysis, the unfavorable prognostic factors were high TNM stage (P < 0.0001), large tumor size (P = 0.0016), high histologic grade (P = 0.0104), and low p27 expression (P < 0.0001). In multivariate analysis, high TNM stage (P = 0.0035) and low p27 expression (P = 0.0235) were independent prognostic factors for disease specific survival in patients with RCC. CONCLUSIONS The results of this study suggest that low p27 expression may be a significant and independent, unfavorable prognostic factor in patients with renal cell carcinoma. Cancer 2002;94:973,9. © 2002 American Cancer Society. DOI 10.1002/cncr.10338 [source] | ||||||||||||||||||||||