Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UNIPROT:P41181 (collecting duct)
 5,183 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Our objective was to compare cancer-specific survival and to examine associations with outcome among the histologic subtypes of renal cell carcinoma (RCC). We studied 2385 patients whose first surgery between 1970 and 2000 was a radical nephrectomy for sporadic, unilateral RCC. All RCC tumors were classified following the 1997 Union Internationale Contre le Cancer and American Joint Committee on Cancer guidelines. There were 1985 (83.2%) patients with clear cell, 270 (11.3%) with papillary, 102 (4.3%) with chromophobe, 6 (0.3%) with collecting duct, 5 (0.3%) with purely sarcomatoid RCC and no underlying histologic subtype, and 17 (0.7%) with RCC, not otherwise specified. Cancer-specific survival rates at 5 years for patients with clear cell, papillary, and chromophobe RCC were 68.9%, 87.4%, and 86.7%, respectively. Patients with clear cell RCC had a poorer prognosis compared with patients with papillary and chromophobe RCC (p <0.001). This difference in outcome was observed even after stratifying by 1997 tumor stage and nuclear grade. There was no significant difference in cancer-specific survival between patients with papillary and chromophobe RCC (p = 0.918). The 1997 TNM stage, tumor size, presence of a sarcomatoid component, and nuclear grade were significantly associated with death from clear cell, papillary, and chromophobe RCC. Histologic tumor necrosis was significantly associated with death from clear cell and chromophobe RCC, but not with death from papillary RCC. Our results demonstrate that there are significant differences in outcome and associations with outcome for the different histologic subtypes of RCC, highlighting the need for accurate subtyping.
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PMID:Comparisons of outcome and prognostic features among histologic subtypes of renal cell carcinoma. 1271 46

Germline mutations of the fumarate hydratase (FH, fumarase) gene are found in the recessive FH deficiency syndrome and in dominantly inherited susceptibility to multiple cutaneous and uterine leiomyomatosis (MCUL). We have previously reported a number of germline FH mutations from MCUL patients. In this study, we report additional FH mutations in MCUL and FH deficiency patients. Mutations can readily be found in about 75% of MCUL cases and most cases of FH deficiency. Some of the more common FH mutations are probably derived from founding individuals. Protein-truncating FH mutations are functionally null alleles. Disease-associated missense FH changes map to highly conserved residues, mostly in or around the enzyme's active site or activation site; we predict that these mutations severely compromise enzyme function. The mutation spectra in FH deficiency and MCUL are similar, although in the latter mutations tend to occur earlier in the gene and, perhaps, are more likely to result in a truncated or absent protein. We have found that not all mutation-carrier parents of FH deficiency children have a strong predisposition to leiomyomata. We have confirmed that renal carcinoma is sometimes part of MCUL, as part of the variant hereditary leiomyomatosis and renal cancer (HLRCC) syndrome, and have shown that these cancers may have either type II papillary or collecting duct morphology. We have found no association between the type or site of FH mutation and any aspect of the MCUL phenotype. Biochemical assay for reduced FH functional activity in the germline of MCUL patients can indicate carriers of FH mutations with high sensitivity and specificity, and can detect reduced FH activity in some patients without detectable FH mutations. We conclude that MCUL is probably a genetically homogeneous tumour predisposition syndrome, primarily resulting from absent or severely reduced fumarase activity, with currently unknown functional consequences for the smooth muscle or kidney cell.
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PMID:Genetic and functional analyses of FH mutations in multiple cutaneous and uterine leiomyomatosis, hereditary leiomyomatosis and renal cancer, and fumarate hydratase deficiency. 1276 Oct 39

Hereditary leiomyomatosis and renal cell cancer (HLRCC) is an autosomal dominant disorder characterized by smooth-muscle tumors of the skin and uterus and/or renal cancer. Although the identification of germline mutations in the fumarate hydratase (FH) gene in European families supports it as the susceptibility gene for HLRCC, its role in families in North America has not been studied. We screened for germline mutations in FH in 35 families with cutaneous leiomyomas. Sequence analysis revealed mutations in FH in 31 families (89%). Twenty different mutations in FH were identified, of which 18 were novel. Of these 20 mutations, 2 were insertions, 5 were small deletions that caused frameshifts leading to premature truncation of the protein, and 13 were missense mutations. Eleven unrelated families shared a common mutation: R190H. Eighty-one individuals (47 women and 34 men) had cutaneous leiomyomas. Ninety-eight percent (46/47) of women with cutaneous leiomyomas also had uterine leiomyomas. Eighty-nine percent (41/46) of women with cutaneous and uterine leiomyomas had a total hysterectomy, 44% at age < or =30 years. We identified 13 individuals in 5 families with unilateral and solitary renal tumors. Seven individuals from four families had papillary type II renal cell carcinoma, and another individual from one of these families had collecting duct carcinoma of the kidney. The present study shows that mutations in FH are associated with HLRCC in North America. HLRCC is associated with clinically significant uterine fibroids and aggressive renal tumors. The present study also expands the histologic spectrum of renal tumors and FH mutations associated with HLRCC.
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PMID:Mutations in the fumarate hydratase gene cause hereditary leiomyomatosis and renal cell cancer in families in North America. 1277 87

Renal oncocytomas account for about 3-7% of all renal tumors. Macroscopically, the cut surface of the tumor is generally mahogany brown or dark red in color. A central scar is occasionally observed. Histologically, tumor cells with finely granular cytoplasm proliferate in an edematous, myxomatous or hyalinized stroma with a nested, tubulocystic, solid or trabecular pattern. Ultrastructurally, tumor cells contain many mitochondria with lamellar cristae. Mitochondrial DNA alterations are consistently observed in renal oncocytomas. In chromosomal analysis, renal oncocytomas comprise a heterogenous group. Combined loss of chromosomes Y and 1, rearrangements affecting band 11q12-13, involvement of 12q12-13, loss of 14q, and the lack of combination of LOH at specific chromosomal sites have been reported. In differential diagnosis, the histological separation from chromophobe RCCs is of great importance. In such a setting, ultrastructural or chromosomal analysis is very useful. However, there are several findings suggesting a close relationship between chromophobe RCC and oncocytoma. First, both tumors share a phenotype of intercalated cells of the collecting duct system and mitochondrial DNA alterations. Second, some cases of coexistent oncocytoma and chromophobe RCC, designated as "renal oncocytosis", have recently been reported. Third, oncocytic variants of chromophobe RCCs that have similar ultrastructural features to those of oncocytomas have been reported. Fourth, the existence of chromophobe adenoma, which is the benign counterpart of chromophobe RCC and shows loss of chromosomes Y and 1, has recently been suggested. Finally, although almost all oncocytomas behave in a benign fashion, some cases of oncocytoma that caused metastasis or resulted in death have also been reported. Therefore, further studies are needed to resolve these problems and also to elucidate the genetic mechanisms responsible for the occurrence of oncocytomas.
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PMID:Review of renal oncocytoma with focus on clinical and pathobiological aspects. 1279 5

A case of sarcomatoid collecting duct carcinoma (CDC) arising in a long-term hemodialysis-associated acquired cystic kidney was reported. A 71-year-old woman with a 21-year history of hemodialysis showed a peritoneal metastatic carcinoma (carcinomatous peritonitis) with an unknown primary site. An autopsy revealed a sarcomatoid collecting duct carcinoma of the right kidney with multicyst formation. In addition to the carcinomatous peritonitis, the tumor metastasized to the lymph nodes and bilateral lung. The primary tumor was composed of both carcinomatous and sarcomatous components, suggesting a high-grade transformation. Carcinomatous tumor cells were positive for epithelial membranous antigen (EMA), cytokeratin, and reactive to soybean agglutinin and peanut agglutinin, whereas the sarcomatous cells were positive for vimentin as well as EMA. Thus, the immunohistochemical and lectin-histochemical analysis confirmed that the tumor originated in the medullary collecting duct. Although CDC is not common in acquired cystic kidney disease patients, attention should be given to the occurrence of high-grade carcinoma of rare histological variant, as well as conventional renal cell carcinoma.
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PMID:Sarcomatoid collecting duct carcinoma arising in the hemodialysis-associated acquired cystic kidney: an autopsy report. 1282 12

Metastatic renal cell carcinoma (RCC) is a disease that is highly resistant to systemic chemotherapy. Responses to combination chemotherapy have been reported in patients with collecting duct carcinoma and the sarcomatoid variant of renal cancer. Clinical trials combining chemotherapy with biologic response modifiers have not resulted in significant advances in the treatment of RCC. Patients with advanced local or metastatic RCC should be offered investigational therapeutic options. The identification of novel agents with significantly improved antitumor activity remains a high priority in the treatment of this disease.
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PMID:Chemotherapeutic strategies for renal cell carcinoma. 1295 58

Renal oncocytomas and chromophobe renal cell carcinomas (RCCs) share a common phenotype and both originate from the intercalated cells of the collecting duct. This makes it very difficult to differentiate between the two tumors immunohistochemically. Therefore, we studied the results of immunohistochemistry focusing on certain characteristic structures that are occasionally present in renal oncocytomas. We carried out Hale's colloidal iron staining and immunohistochemistry for various cytokeratins (cytokeratins 7, 8, 10, 10/13, 14, 18, 19 and 20, and AE1/AE3) in four oncocytomas and six chromophobe RCCs. In addition, one renal oncocytoma and one chromophobe RCC were studied using electron microscopy. Two renal oncocytomas and one chromophobe RCC were completely unstained by colloidal iron. There was no evident difference between the immunohistochemical characteristics of oncocytomas and those of chromophobe RCCs. However, in all four renal oncocytomas we identified intracytoplasmic ring-like positive reactions for some cytokeratins (at least 3 antigens of cytokeratins 7, 8 and 19, and AE1/AE3), which corresponded ultrastructurally to the intracytoplasmic lumens (ICLs). In contrast, no such structures were found in any of the chromophobe RCCs using the antibodies employed. Therefore, immunohistochemical identification of ICLs by cytokeratin typing may be useful for differentiating between renal oncocytomas and chromophobe RCCs and be more sensitive in this respect than colloidal iron staining.
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PMID:Immunohistochemical identification of intracytoplasmic lumens by cytokeratin typing may differentiate renal oncocytomas from chromophobe renal cell carcinomas. 1470 67

To elucidate the relationship between tumor genesis and the mitochondrial energy metabolism in renal neoplasms, we studied three individual enzyme activities of the oxidative phosphorylation, two components of the Krebs cycle and the mitochondrial DNA content of renal carcinomas including 29 conventional, five papillary, two unclassified carcinomas with sarcomatoid features and one collecting duct carcinoma. A significant reduction of all mitochondrial enzyme activities including complex V, as well as of the mitochondrial DNA content was detected in 34 of 37 renal carcinoma tissues as compared with control kidney. Mitochondrial enzyme activities and mitochondrial DNA levels were not statistically different between the conventional, papillary and unclassified sarcomatoid type of renal carcinoma and did not correlate with tumour grade, metastasis, ploidy and proliferative activity as determined by Ki-67 staining. Taken together, our data indicate that a co-ordinated down-regulation of all components necessary for mitochondrial energy metabolism occurs in most renal carcinomas as an early event in carcinoma formation, which does not change with progression of the disease.
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PMID:Decrease of mitochondrial DNA content and energy metabolism in renal cell carcinoma. 1476 59

We report a rare collision tumor of a nodule-in-nodule pattern between a clear cell-type carcinoma and a collecting duct carcinoma in a 24-year-old man. Whereas the outer nodule is quite different from the 'conventional renal cell carcinoma (RCC)' with respect to vascularity, the inner nodule is quite distinctive as regards immunophenotype and karyotype results. Karyotyping the latter by means of comparative genomic hybridization (CGH) disclosed gains of chromosome regions in 1q21.2-qter, 5q21-qter, 6q16.3-qter and 17q21.2-qter along with a loss in 1p21-p31.14, 9q31-pter, 11, 13q12-qter, 15q12-qter and 18q21.1-qter. The clear cell carcinoma surrounding the daughter nodule revealed no 3p loss by means of CGH, unlike most cases of conventional RCC that are seemingly associated with poor vasculature. In summary, to our knowledge, this is the first reported case of an unclassified RCC featuring a unique growth pattern composed of a mixed clear cell type without a 3p loss and a variant of CDC with a unique karyotypic alteration.
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PMID:Simultaneous heterogenotypic renal cell carcinoma: immunohistochemical and karyoptic analysis by comparative genomic hybridization. 1515 36

KIT expression has not been studied substantially in renal tumors. We analyzed the immunohistochemical expression for KIT in 256 conventional renal cell carcinomas (RCCs), 29 chromophobe RCCs, 25 papillary RCCs, 6 collecting duct RCCs, 6 unclassified RCCs, 7 renal oncocytomas, 20 urothelial carcinomas, 7 nephroblastomas, and 23 angiomyolipomas. We found that 24 chromophobe RCCs (83%) and 5 renal oncocytomas (71%) revealed membranous immunoreactivity for KIT while none of the RCCs of other types expressed KIT immunohistochemically. Sporadic cases of urothelial carcinoma and nephroblastoma were focally positive for KIT. All angiomyolipomas were negative. Genomic DNA extracted from the chromophobe RCCs and renal oncocytomas was submitted for polymerase chain reaction and direct sequencing of the juxtamembrane (exons 9 and 11) and tyrosine kinase (exons 13 and 17) domains. No mutation was found. Our results demonstrate that KIT could be a useful immunophenotypic marker for chromophobe RCC and renal oncocytoma; therefore, it has value for the precise classification of renal cortical epithelial tumors. However, the therapeutic relevance of KIT overexpression in these tumors is uncertain owing to the lack of mutations that would lead to constitutive activation of the protein.
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PMID:Overexpression of KIT (CD117) in chromophobe renal cell carcinoma and renal oncocytoma. 1519 61


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