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Jonathan I Epstein - One of the best experts on this subject based on the ideXlab platform.
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immunohistochemical analysis of smarcb1 ini 1 expression in Collecting Duct Carcinoma
Urology, 2011Co-Authors: Hillary Elwood, Jonathan I Epstein, Alcides Chaux, Luciana Schultz, Peter B Illei, Dilek Ertoy Baydar, A Billis, Rajni Sharma, Pedram Argani, George J NettoAbstract:Objectives Collecting Duct Carcinoma (CDC) is a rare and aggressive renal tumor with a tendency to involve the renal sinus. CDC displays variable morphologic features that can overlap with those of renal medullary Carcinoma. The loss of SMARCB1 / INI1 tumor suppressor gene, initially found in pediatric malignant rhabdoid tumors of the central nervous system, kidneys, and soft tissues, was also recently described in renal medullary Carcinoma. The current immunohistochemical study assessed SMARCB1/INI1 expression in a series of CDCs. Methods A total of 20 archival cases of CDC were used to construct a tissue microarray. Each tumor was spotted 3-7 times; benign tissue from the same specimen was also included when available. The immunoexpression of SMARCB1/INI1 was evaluated using BAF47, a monoclonal mouse antibody directed against the SMARCB1 / INI1 gene proDuct. Nuclear staining was considered as indicative of SMARCB1/INI1 expression. Results The complete loss of SMARCB1/INI1 expression was observed in 3 of 20 cases of CDC. Another 3 cases revealed focal and weak intensity staining. The remaining tumors showed multifocal or diffuse SMARCB1/INI1 expression with variable staining intensity. No significant differences were found in the clinicopathologic and outcome features regarding SMARCB1/INI1 status. Conclusions The complete loss of SMARCB1/INI1 immunoexpression was found in 15% of CDC. No differences were found between the SMARCB1/INI1 positive and negative cases regarding the clinicopathologic and outcome features. Our results suggest that some CDC cases might be associated with genetic alterations involving the SMARCB1/INI1 gene. In addition, SMARCB1/INI1 immunoexpression seems to be of limited value in the differential diagnosis of CDC versus renal medullary Carcinoma, although these results require additional validation.
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comparison of gene expression profiles in tubulocystic Carcinoma and Collecting Duct Carcinoma of the kidney
The American Journal of Surgical Pathology, 2009Co-Authors: Adeboye O Osunkoya, Andrew N Young, Wenle Wang, George J Netto, Jonathan I EpsteinAbstract:The relationship between tubulocystic Carcinoma and Collecting Duct Carcinoma of the kidney remains controversial. Some experts are of the opinion that the tumors are related, considering tubulocystic Carcinoma to be synonymous with low-grade Collecting Duct Carcinoma. However, others maintain that the 2 are distinct, unrelated entities on the basis of morphologic features and clinical outcome. To explore the relationship between tubulocystic Carcinoma and Collecting Duct Carcinoma, we compared the expression of several gene proDucts at the mRNA level in cohorts of each tumor subtype. Seven cases of tubulocystic Carcinoma and 8 cases of Collecting Duct Carcinoma were identified. Total RNA was isolated from formalin-fixed paraffin-embedded tissue from each case. Relative expression levels of vimentin, alpha methylacyl CoA racemase, E-cadherin, p53, CD10 antigen, parvalbumin, cytokeratin 7, and cytokeratin 19 were assessed by quantitative reverse transcription polymerase chain reaction. Tubulocystic Carcinoma was characterized by relative overexpression of vimentin, p53, and alpha methylacyl CoA racemase, compared with Collecting Duct Carcinoma (P<0.05 for each gene, t test). In general, tubulocystic Carcinoma expressed higher levels of E-cadherin and CD10, whereas Collecting Duct Carcinoma expressed higher levels of cytokeratin 19; however, these trends did not reach statistical significance in this study cohort. Tubulocystic Carcinoma and Collecting Duct Carcinoma did not express cytokeratin 7 differentially. Case-to-case variability of gene expression limited the effectiveness of any one marker to distinguish the tumor types. Our study demonstrates that tubulocystic Carcinoma and Collecting Duct Carcinoma have different expression profiles of selected genes, including vimentin, p53, and alpha methylacyl CoA racemase. Further analysis of additional cases, using quantitative reverse transcription polymerase chain reaction and immunohistochemistry, will be useful to test the reproducibility of these findings. In addition, larger studies may establish statistical differences in expression of other genes analyzed in this study. Overall, these findings support the view that tubulocystic Carcinoma and Collecting Duct Carcinoma should be considered as 2 distinct entities at the molecular level.
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high density mapping of chromosomal arm 1q in renal Collecting Duct Carcinoma region of minimal deletion at 1q32 1 32 2
Cancer Research, 1996Co-Authors: Gabriel Steiner, Jonathan I Epstein, Fray F Marshall, Paul Cairns, David Sidransky, Thomas J Polascik, Mark P SchoenbergAbstract:Collecting Duct Carcinoma (CDC) of the kidney is a rare malignant neoplasm of distal nephron origin. Previous studies of CDC have shown loss of heterozygosity on chromosomal arm 1q in 57% of the cases studied. To better characterize 1q loss in CDC, we performed high-density mapping of the entire long arm of chromosome 1 in 13 CDC tumor samples. We observed complete deletion of chromosomal arm 1q in 5 samples and partial deletion in 4 additional tumors. Our study further showed that the region of minimal deletion is located at 1q32.1–32.2 Sixty-nine percent (9 of 13) of the tumors showed loss of heterozygosity in this area. These data suggest that a gene or group of genes that contribute to the development of distal nephron tumors may be located within the 1q32.1–32.2 region.
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frequent loss of chromosome arms 8p and 13q in Collecting Duct Carcinoma cdc of the kidney
Genes Chromosomes and Cancer, 1995Co-Authors: Mark P Schoenberg, Jonathan I Epstein, James D Brooks, Fray F Marshall, William B Isaacs, Paul Cairns, David SidranskyAbstract:Collecting Duct Carcinoma (CDC) is a malignant renal neoplasm that is believed to arise from the epithelium of the Ducts of Bellini in the distal nephron. These tumors are clinically aggressive and more often occur in a younger population than is typical of the more common clear cell renal Carcinoma (RCC). Using highly informative polymorphic microsatellite markers on chromosome arms 3p, 5q, 6q, 9p, 9q, 11p, 13q, 17p, and 18q, we analyzed DNA from nonmalignant and tumor tissue in 6 cases of CDC. We found no evidence of 3p loss of heterozygosity (LOH) in these renal tumors by using multiple markers, a finding that distinguishes CDC from RCC in which 3p LOH has frequently been observed. We found LOH of 8p in 50% of the tumors examined; in addition, we observed LOH of 13q in 50% of the tumors studied. Interestingly, 8p LOH may be associated with high stage and poor clinical prognosis. These data suggest that the molecular events responsible for the development of CDC differ from those associated with the origin of RCC, and that tumor suppressor genes on 8p and 13q may be involved in the pathogenesis of CDC.
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frequent loss of chromosome arms 8p and 13q in Collecting Duct Carcinoma cdc of the kidney
Genes Chromosomes and Cancer, 1995Co-Authors: Mark P Schoenberg, Jonathan I Epstein, James D Brooks, Fray F Marshall, William B Isaacs, Paul Cairns, David SidranskyAbstract:Collecting Duct Carcinoma (CDC) is a malignant renal neoplasm that is believed to arise from the epithelium of the Ducts of Bellini in the distal nephron. These tumors are clinically aggressive and more often occur in a younger population than is typical of the more common clear cell renal Carcinoma (RCC). Using highly informative polymorphic microsatellite markers on chromosome arms 3p, Sq, 6q, 8p, 9p, 9q, I I p, I 3q, I7p, and I8q, we analyzed DNA from nonmalignant and tumor tissue in 6 cases of CDC. We found no evidence of 3p loss of heterozygosity (LOH) in these renal tumors by using multiple markers, a finding that distinguishes CDC from RCC in which 3p LOH has frequently been observed. We found LOH of 8p in 50% of the tumors examined; in addition, we observed LOH of 13q in 50% of the tumors studied. Interestingly, 8p LOH may be associated with high stage and poor clinical prognosis. These data suggest that the molecular events responsible for the development of CDC differ from those associated with the origin of RCC, and that tumor suppressor genes on 8p and 13q may be involved in the pathogenesis of CDC. Genes Chromosam Cancer 12:76-80 (1995). 0 1995 Wiley-Liss. Inc.
George J Netto - One of the best experts on this subject based on the ideXlab platform.
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immunohistochemical analysis of smarcb1 ini 1 expression in Collecting Duct Carcinoma
Urology, 2011Co-Authors: Hillary Elwood, Jonathan I Epstein, Alcides Chaux, Luciana Schultz, Peter B Illei, Dilek Ertoy Baydar, A Billis, Rajni Sharma, Pedram Argani, George J NettoAbstract:Objectives Collecting Duct Carcinoma (CDC) is a rare and aggressive renal tumor with a tendency to involve the renal sinus. CDC displays variable morphologic features that can overlap with those of renal medullary Carcinoma. The loss of SMARCB1 / INI1 tumor suppressor gene, initially found in pediatric malignant rhabdoid tumors of the central nervous system, kidneys, and soft tissues, was also recently described in renal medullary Carcinoma. The current immunohistochemical study assessed SMARCB1/INI1 expression in a series of CDCs. Methods A total of 20 archival cases of CDC were used to construct a tissue microarray. Each tumor was spotted 3-7 times; benign tissue from the same specimen was also included when available. The immunoexpression of SMARCB1/INI1 was evaluated using BAF47, a monoclonal mouse antibody directed against the SMARCB1 / INI1 gene proDuct. Nuclear staining was considered as indicative of SMARCB1/INI1 expression. Results The complete loss of SMARCB1/INI1 expression was observed in 3 of 20 cases of CDC. Another 3 cases revealed focal and weak intensity staining. The remaining tumors showed multifocal or diffuse SMARCB1/INI1 expression with variable staining intensity. No significant differences were found in the clinicopathologic and outcome features regarding SMARCB1/INI1 status. Conclusions The complete loss of SMARCB1/INI1 immunoexpression was found in 15% of CDC. No differences were found between the SMARCB1/INI1 positive and negative cases regarding the clinicopathologic and outcome features. Our results suggest that some CDC cases might be associated with genetic alterations involving the SMARCB1/INI1 gene. In addition, SMARCB1/INI1 immunoexpression seems to be of limited value in the differential diagnosis of CDC versus renal medullary Carcinoma, although these results require additional validation.
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comparison of gene expression profiles in tubulocystic Carcinoma and Collecting Duct Carcinoma of the kidney
The American Journal of Surgical Pathology, 2009Co-Authors: Adeboye O Osunkoya, Andrew N Young, Wenle Wang, George J Netto, Jonathan I EpsteinAbstract:The relationship between tubulocystic Carcinoma and Collecting Duct Carcinoma of the kidney remains controversial. Some experts are of the opinion that the tumors are related, considering tubulocystic Carcinoma to be synonymous with low-grade Collecting Duct Carcinoma. However, others maintain that the 2 are distinct, unrelated entities on the basis of morphologic features and clinical outcome. To explore the relationship between tubulocystic Carcinoma and Collecting Duct Carcinoma, we compared the expression of several gene proDucts at the mRNA level in cohorts of each tumor subtype. Seven cases of tubulocystic Carcinoma and 8 cases of Collecting Duct Carcinoma were identified. Total RNA was isolated from formalin-fixed paraffin-embedded tissue from each case. Relative expression levels of vimentin, alpha methylacyl CoA racemase, E-cadherin, p53, CD10 antigen, parvalbumin, cytokeratin 7, and cytokeratin 19 were assessed by quantitative reverse transcription polymerase chain reaction. Tubulocystic Carcinoma was characterized by relative overexpression of vimentin, p53, and alpha methylacyl CoA racemase, compared with Collecting Duct Carcinoma (P<0.05 for each gene, t test). In general, tubulocystic Carcinoma expressed higher levels of E-cadherin and CD10, whereas Collecting Duct Carcinoma expressed higher levels of cytokeratin 19; however, these trends did not reach statistical significance in this study cohort. Tubulocystic Carcinoma and Collecting Duct Carcinoma did not express cytokeratin 7 differentially. Case-to-case variability of gene expression limited the effectiveness of any one marker to distinguish the tumor types. Our study demonstrates that tubulocystic Carcinoma and Collecting Duct Carcinoma have different expression profiles of selected genes, including vimentin, p53, and alpha methylacyl CoA racemase. Further analysis of additional cases, using quantitative reverse transcription polymerase chain reaction and immunohistochemistry, will be useful to test the reproducibility of these findings. In addition, larger studies may establish statistical differences in expression of other genes analyzed in this study. Overall, these findings support the view that tubulocystic Carcinoma and Collecting Duct Carcinoma should be considered as 2 distinct entities at the molecular level.
Stephane Oudard - One of the best experts on this subject based on the ideXlab platform.
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triple combination of bevacizumab gemcitabine and platinum salt in metastatic Collecting Duct Carcinoma
Annals of Oncology, 2013Co-Authors: Nicolas Pecuchet, Bernard Escudier, Frederic Bigot, Julie Gachet, Christophe Massard, Laurence Albiges, C Teghom, Yves Allory, Arnaud Mejean, Stephane OudardAbstract:Background Collecting Duct Carcinoma (CDC) is a rare and aggressive subtype of kidney cancer that responds to platinum-based chemotherapy. Recent phase II trials have established enhanced antitumor activity on combining bevacizumab with chemotherapy in patients with metastatic urothelial Carcinoma, a tumor that shares many features with CDC. Our aim was to investigate whether combining bevacizumab with platinum-based chemotherapy might not also show promise in metastatic CDC (mCDC) patients. Patients and methods Five previously untreated patients diagnosed with mCDC received bevacizumab (15 mg/kg) in combination with gemcitabine (1250 mg/m(2), D1-D8) and platinum salt (cisplatin 80 mg/m(2) or carboplatin AUC 5 mg/ml/min) every 3 weeks for up to six cycles. This was followed by bevacizumab maintenance therapy (15 mg/kg). Results All five patients (median age, 62 years; range 45-66 years) had an Eastern Cooperative Oncology Group PS of 0-1. They received the triple-drug combination for a median of four cycles (range, 2-6) and bevacizumab maintenance therapy for a median of three cycles (range, 0-17). There were three cases of partial response, one case of stable disease (20 months) and one case of complete remission after surgery of the only metastatic site. Median progression-free survival (PFS) was 15.1 months [95% confidence interval (CI) 5.6-20.4]. Median overall survival (OS) was 27.8 months (95% CI 12.4-unreached). Grades 3 or 4 adverse events were pulmonary embolism (n = 2), neutropenia (n = 2), thrombopenia (n = 1), asthenia (n = 1) and hypertension (n = 1). Conclusions The addition of bevacizumab to platinum-based chemotherapy resulted in a longer PFS and longer OS than recorded in an earlier clinical trial of platinum-based chemotherapy alone. The triple combination was manageable. The French Collaborative Group (Groupe d'Etudes des Tumeurs Uro-Genitales) is planning a prospective multicenter phase II clinical trial of the triple combination in mCDC patients. Clinical trial BEVABEL/MO28644 (EudraCT: 2013-001179-19).
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prospective multicenter phase ii study of gemcitabine plus platinum salt for metastatic Collecting Duct Carcinoma results of a getug groupe d etudes des tumeurs uro genitales study
The Journal of Urology, 2007Co-Authors: Stephane Oudard, E Banu, Annick Vieillefond, L Fournier, Franck Priou, Jacques Medioni, A Banu, Brigitte Duclos, Frederic Rolland, Bernard EscudierAbstract:Purpose: Collecting Duct Carcinoma of the kidney is a rare and aggressive neoplasm of the distal Collecting tubules for which there is no established treatment. Since the histology of Collecting Duct Carcinoma is similar to that of urothelial Carcinoma, the standard chemotherapy regimen defined by a gemcitabine and platinum salts combination was prospectively investigated in patients with metastatic Collecting Duct Carcinoma.Materials and Methods: A total of 23 patients with metastatic Collecting Duct Carcinoma with no prior systemic chemotherapy were treated with 1,250 mg/m2 gemcitabine on days 1 and 8 plus 70 mg/m2 cisplatin or carboplatin (AUC 5) in patients with renal insufficiency on day 1. The drugs were repeated every 21 days for 6 cycles according to toxicity and efficacy. The objective response rate was the primary end point.Results: There were 1 complete and 5 partial responses for an objective response rate of 26% (95% CI 8 to 44). Median progression-free and overall survival was 7.1 (95% CI 3 ...
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Collecting Duct Carcinoma of the kidney a clinicopathological study of 9 cases
The Journal of Urology, 2003Co-Authors: Michael Peyromaure, Annick Vieillefond, N Thiounn, Florian Scotte, Bernard Debre, Stephane OudardAbstract:ABSTRACTPurpose: Collecting Duct Carcinoma (CDC) of the kidney is a rare variant that is associated with an extremely poor prognosis. We report our experience with this variety of cancer in the last 9 years.Materials and Methods: From 1993 to 2002, 9 patients with CDC were treated at our institution. The diagnosis of CDC was made by a nephrectomy specimen in 8 cases and by renal biopsy in 1. Tumor characteristics, and patient treatment and outcome are reported.Results: At presentation 1 T1N0M0, 1 T3N0M0, 3 T3N+M0 and 4 T3N+M+ tumors were seen. Mean followup was 13.6 months. Five patients received no complementary treatment. The patient with the T1N0M0 tumor remained free of disease 13 months after nephrectomy and the one with T3N0M0 tumor remained free of disease at 17 months. A patient with a T3N+M+ tumor experienced progression at 1 month, local recurrence at 17 months and was then lost to followup. The 2 other patients with T3N+M0 and T3N+M+ disease, respectively, progressed rapidly and were lost to fo...
David G Grignon - One of the best experts on this subject based on the ideXlab platform.
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sarcomatoid Collecting Duct Carcinoma a clinicopathologic and immunohistochemical study of five cases
Human Pathology, 1993Co-Authors: Nelson G Ordonez, Susan C Baer, Russell L Maiese, Jeffrey H Loose, David G GrignonAbstract:Sarcomatoid renal cell Carcinoma is a well-known entity, but sarcomatoid Collecting Duct Carcinoma has not been reported. We recently encountered five cases. The patients were men whose ages ranged from 59 to 82 years (mean age, 68 years). All presented with gross hematuria and three had abdominal fullness. Tumor size ranged from 6 to 9 cm in greatest dimension. The Fuhrman's nuclear grade of the Carcinomatous components was 3 in three cases and 4 in two. The sarcomatoid areas were composed of pleomorphic spindle cells forming a malignant fibrous histiocytomatous pattern in four cases and a fibrosarcomatous pattern in one. The immunohistochemical findings in the Carcinomatous and sarcomatoid components were identical. Wide-spectrum anti-cytokeratin cocktail, epithelial membrane antigen, and vimentin antibodies demonstrated immunoreactivity, while Leu-M1 did not react in all five cases. Three of the five tumors were positive for Ulex europaeus agglutinin I lectin. One sarcomatoid Carcinoma reacted with monoclonal antibody to high molecular weight keratins, and all five tumors reacted with a monoclonal antibody to low molecular weight keratins. Two patients died at 5 months and 13 months after diagnosis, two are alive with metastatic disease at 1 and 14 months, and one is alive with no evidence of disease at 36 months.
Bernard Escudier - One of the best experts on this subject based on the ideXlab platform.
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triple combination of bevacizumab gemcitabine and platinum salt in metastatic Collecting Duct Carcinoma
Annals of Oncology, 2013Co-Authors: Nicolas Pecuchet, Bernard Escudier, Frederic Bigot, Julie Gachet, Christophe Massard, Laurence Albiges, C Teghom, Yves Allory, Arnaud Mejean, Stephane OudardAbstract:Background Collecting Duct Carcinoma (CDC) is a rare and aggressive subtype of kidney cancer that responds to platinum-based chemotherapy. Recent phase II trials have established enhanced antitumor activity on combining bevacizumab with chemotherapy in patients with metastatic urothelial Carcinoma, a tumor that shares many features with CDC. Our aim was to investigate whether combining bevacizumab with platinum-based chemotherapy might not also show promise in metastatic CDC (mCDC) patients. Patients and methods Five previously untreated patients diagnosed with mCDC received bevacizumab (15 mg/kg) in combination with gemcitabine (1250 mg/m(2), D1-D8) and platinum salt (cisplatin 80 mg/m(2) or carboplatin AUC 5 mg/ml/min) every 3 weeks for up to six cycles. This was followed by bevacizumab maintenance therapy (15 mg/kg). Results All five patients (median age, 62 years; range 45-66 years) had an Eastern Cooperative Oncology Group PS of 0-1. They received the triple-drug combination for a median of four cycles (range, 2-6) and bevacizumab maintenance therapy for a median of three cycles (range, 0-17). There were three cases of partial response, one case of stable disease (20 months) and one case of complete remission after surgery of the only metastatic site. Median progression-free survival (PFS) was 15.1 months [95% confidence interval (CI) 5.6-20.4]. Median overall survival (OS) was 27.8 months (95% CI 12.4-unreached). Grades 3 or 4 adverse events were pulmonary embolism (n = 2), neutropenia (n = 2), thrombopenia (n = 1), asthenia (n = 1) and hypertension (n = 1). Conclusions The addition of bevacizumab to platinum-based chemotherapy resulted in a longer PFS and longer OS than recorded in an earlier clinical trial of platinum-based chemotherapy alone. The triple combination was manageable. The French Collaborative Group (Groupe d'Etudes des Tumeurs Uro-Genitales) is planning a prospective multicenter phase II clinical trial of the triple combination in mCDC patients. Clinical trial BEVABEL/MO28644 (EudraCT: 2013-001179-19).
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prospective multicenter phase ii study of gemcitabine plus platinum salt for metastatic Collecting Duct Carcinoma results of a getug groupe d etudes des tumeurs uro genitales study
The Journal of Urology, 2007Co-Authors: Stephane Oudard, E Banu, Annick Vieillefond, L Fournier, Franck Priou, Jacques Medioni, A Banu, Brigitte Duclos, Frederic Rolland, Bernard EscudierAbstract:Purpose: Collecting Duct Carcinoma of the kidney is a rare and aggressive neoplasm of the distal Collecting tubules for which there is no established treatment. Since the histology of Collecting Duct Carcinoma is similar to that of urothelial Carcinoma, the standard chemotherapy regimen defined by a gemcitabine and platinum salts combination was prospectively investigated in patients with metastatic Collecting Duct Carcinoma.Materials and Methods: A total of 23 patients with metastatic Collecting Duct Carcinoma with no prior systemic chemotherapy were treated with 1,250 mg/m2 gemcitabine on days 1 and 8 plus 70 mg/m2 cisplatin or carboplatin (AUC 5) in patients with renal insufficiency on day 1. The drugs were repeated every 21 days for 6 cycles according to toxicity and efficacy. The objective response rate was the primary end point.Results: There were 1 complete and 5 partial responses for an objective response rate of 26% (95% CI 8 to 44). Median progression-free and overall survival was 7.1 (95% CI 3 ...