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Query: UMLS:C0403608 (ureter)
 9,655 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Three inherited types of large bowel cancer not associated with polyposis were previously proposed. A fourth should also be added to the list, namely, Torre's or Muir's syndrome. This report summarizes the clinical and genetic features of that syndrome in one family. The principle features of the syndrome comprise multiple skin tumors, i.e., sebaceous adenomas, keratoacanthomas, and basal and squamous cell carcinomas occurring with polyps and adenocarcinomas, mainly of the large bowel and also of the small intestine and stomach. Other malignancies occurring with the multiple skin tumors, with or without the involvement of intestinal malignancies, included adenocarcinoma of the uterus, transitional cell carcinoma of the bladder or ureter, squamous cell carcinoma of the larynx, esophagus, or vulva, and cancer of the breast. The syndrome followed a dominant mode of inheritance with high penetrance and variable expressivity, perhaps more variable in females than in males.
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PMID:An inherited form of large bowel cancer: Muir's syndrome. 735 6

A 41-year-old man was admitted to the hospital complaining of mild epigastralgia. Radiographic examinations revealed a right intrapelvic solid tumor (5 x 3 cm) apparently causing stenosis of the right ureter at the level of pelvic brim. The patient underwent an operation. The tumor which invaded the ileum and ureter was excised with resection of the affected segment of ileum and nephroureterectomy. Histological diagnosis was mesenteric fibromatosis. Barium enema study revealed no polyposis of the colon postoperatively. One year after surgery the patient has no signs of recurrence.
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PMID:[Mesenteric fibromatosis with hydronephrosis: a case report]. 817 44

Hereditary non-polyposis colorectal cancer (HNPCC) is an autosomal, dominantly inherited disease leading to a marked increase in cancer susceptibility, notably colorectal cancer, affecting up to one in 400 individuals in the Western world. Four genes responsible for the majority of cases have been identified. Colorectal cancer in affected people tends to be right sided, occur at an earlier age, and there is a propensity for synchronous or metachronous lesions. Extra-colonic tumours may occur with an elevated frequency, most importantly cancer of the endometrium, but also stomach, hepatobiliary system, small bowel, proximal ureter and renal pelvis, and ovary. On account of these features, management guidelines for members of HNPCC kindreds require modification from those generally advised for patients with sporadic tumours. The cardinal feature for the identification of affected families is the family history. All clinicians have a duty to identify such patients under their care as appropriate screening and surgery should lead to an improved prognosis for such patients and their families.
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PMID:[Hereditary nonpolyposis colorectal cancers]. 884 75

Effective prevention of cancer in patients with a hereditary disposition to malignant tumours was made possible by intensive prevention programs and molecular diagnosis. Taken hereditary non-polyposis colorectal cancer (HNPCC) as an example this article deals with the pathogenesis and molecular diagnosis in hereditary dispositions to cancer. HNPCC is inherited in an autosomal-dominant fashion and caused by germline mutations in genes responsible for detection an removal of DNA-basepair-mismatches (DNA-mismatch-repair-genes). The error rate in DNA replication is reduced thousandfold by these genes. A defective DNA-mismatch-repair results in tumours if the increased mutation rate causes alterations of tumour-suppressor- or oncogenes. HNPCC patients develop colorectal cancer but also tumours of the renal pelvis, the ureter, the small bowel, the endometrium and less often in other organs. The clinical presentation of these tumours may be characteristic, the clinical diagnosis may be guided by different clinical criteria catalogues. The suspicion is proven by the identification of a germline mutation in DNA-mismatch-repair-genes. This laborious diagnostic procedure is often preceded by prescreening procedures as the detection of microsatellite instability or immunohistochemical tests. Once the germline mutation is identified in a affected family member, the first degree relatives may be tested for this mutation. If they have inherited the mutation, they harbour a extremely high risk for developing cancer and therefore may be included in prevention programs. This so called predictive testing must be preceded by genetic counseling.
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PMID:[Hereditary carcinoma: pathogenesis and diagnosis]. 1092 39

Inherited defects of the DNA mismatch repair system are the underlying cause of the hereditary non-polyposis colorectal cancer (HNPCC) syndrome and are responsible for 3-4% of all cases of colorectal cancer. The HNPCC syndrome also carries the risk of development of additional malignancies such as endometrial, stomach, small bowel, ovarian, pancreas, ureter, renal pelvis, biliary tract and brain tumours. Amsterdam I and II criteria have been developed to clinically identify affected families. The revised Bethesda criteria function to select patients whose tumours should be investigated for microsatellite instability, the molecular hallmark of defects of the DNA mismatch repair proteins such as hMLH1 and hMSH2. Microsatellite instability-positive cases should be investigated for germline defects in the respective genes. This facilitates identification of affected family members that have to be included in special surveillance programmes, while unaffected family members are spared the physical discomfort and psychological burden of cancer surveillance. In this article, strategies for effective clinical as well as genetic detection of affected individuals, surveillance and appropriate preventive measures are discussed. Open questions include the role of chemoprevention, preventive surgical procedures, new endoscopic procedures as well as non-invasive 'virtual colonoscopy' and the exact implications of some mutations of the DNA mismatch repair genes. Perhaps most importantly, efforts should be made to more efficiently transfer information about the HNPCC syndrome and the cancer risk associated with it from the specialists to primary health care providers and the general public.
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PMID:Critical issues in the identification and management of patients with hereditary non-polyposis colorectal cancer. 1635 31

The majority of tumours in patients with hereditary non-polyposis colon cancer (HNPCC) occur in large intestine and endometrium; also, other tissues are at increased risk. We studied expression of hMLH1 and hMSH2 proteins in 148 normal samples of various tissues from non-HNPCC patients and in 14 normal colon tissues from HNPCC patients. Immunohistochemical technique was used. Intensity of nuclear staining, percentage of stained cells and H-scores were calculated. Tissues were divided into groups. Groups A, B and C included tissues with increased risk of cancer in HNPCC A) stomach, small and large bowel; (B) endometrium; (C) ovary, ureter, urinary bladder, kidney and liver. Group D tissues were without increased risk. Expression of the proteins was significantly higher in groups A, B and C compared with group D (P<0.0001, P=0.0004 for hMSH2 in C versus D). The expression was highest in testis. In colons of HNPCC patients, expression of the mutated gene product was significantly lower than in non-HNPCC patients. In conclusion, hMLH1/hMSH2 protein expression is constitutively higher in certain cell types of certain tissues, including the majority of tissues that are at increased risk of cancer in HNPCC. However, association of strong hMLH1/hMSH2 expression with cancer risk is not strictly valid.
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PMID:Expression of the hMLH1 and hMSH2 proteins in normal tissues: relationship to cancer predisposition in hereditary non-polyposis colon cancer. 1573 76

The family histories of 130 individuals with documented hereditary non-polyposis colorectal cancer (HNPCC) (caused by mutations in mismatch-repair (MMR) genes MSH2 (n = 64), MLH1 (n = 62) or MSH6 (n = 4)) were obtained, and incidence of cancers in those families was compared to that in the general population. There were a total of 982 cancers in 723 individuals. Colorectal cancer (CRC) was the commonest type (64% and 55% in individuals from families with germline MLH1 and MSH2 mutations respectively). Median age at diagnosis of first CRC in MSH6 mutation families was 59 years compared to 45 years in both MLH1 and MSH2 mutation families. The relative risk (RR) of endometrial cancer was 55 in MSH2 mutation families, compared with 27 in MLH1 mutation families, and 37 in MSH6 mutation families; median age at diagnosis 49 years. Even within MSH2 families, endometrial cancer tended to cluster, with 28 of the 58 cases coming from families with three or more cases (P < 0.001). Absolute risk of endometrial cancer in MLH1 families was still greater than any other cancer (other than CRC). 5% of cancers in both MLH1 and MSH2 mutation families were gastric (RR = 12); 53% of these were diagnosed before 50 years. Seven cases of small intestinal cancer occurred in MSH2 and MLH1 mutation families (RR = 26). There were 13 cases of cancer of the ureter; all were in MSH2 families. These cancers tended to cluster within families (P < 0.001); three of seven families with urothelial cancer had such cases in two or more individuals; two others had kidney cancer. Nineteen of 27 ovarian cancers (70%) were in MSH2 mutation families and 70% of these were diagnosed before age 50 years. There were 9 cases of sebaceous skin cancer, 3 in two MLH1 and 6 in four MSH2 mutation families. Of 22 pancreatic cancers, 14 were known to be diagnosed before 60 years. Breast cancer RR was 1.7 overall. The type of mutation (truncating or other type, and site of mutation) showed no obvious correlation with the presence or absence of extra-colonic cancers in families.
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PMID:Gene-related cancer spectrum in families with hereditary non-polyposis colorectal cancer (HNPCC). 1793 62

Hereditary non-polyposis colorectal cancer (HNPCC) is an autosomal dominant disease, characterized by the occurrence of predominantly colon and endometrial cancer and, less frequently, cancer of the small bowel, stomach, hepatobiliary tract, ureter, renal pelvis, ovaries and brain. The phenotypic diversity may partially be explained by allelic heterogeneity. The aim of this study was to investigate the frequency of extracolonic cancers in a cohort of females sharing the same c.C1528T disease-predisposing mutation in the hMLH1 gene. Data on cancer history were obtained from 87 mutation-positive females and 121 mutation-negative sisters, as a control group. Testing for microsatellite instability (MSI) and expression of the wild-type hMLH1 allele was performed on extra-colonic tumour tissue blocks of mutation-positive individuals. Extracolonic cancer occurred in 14% (12/87) of mutation-positive females vs. 7% (8/121) of mutation-negative females (P = 0.10). Multiple primary cancers occurred at a significantly higher incidence in the first group. Breast cancer, which was the most frequent extra-colonic cancer in mutation positive females (53%), occurred at a young age, and occurred bilaterally in two out of seven cases. Involvement of the hMLH1 gene was confirmed in five out of seven cases of breast cancer, two cases of endometrial cancer, one case of ovarian cancer and one case of renal cell carcinoma, by detecting immunohistochemical compromise of the gene product. Although the study might not have been adequately statistically powered (to provide a significant P value), the noteworthy findings in this study include the confirmation of a range of Lynch II type cancers in a cohort we previously thought was wholly predisposed to Lynch I features, and a confirmation of breast cancer as part of the spectrum of Lynch syndrome cancers affecting women.
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PMID:The extracolonic cancer spectrum in females with the common 'South African' hMLH1 c.C1528T mutation. 1804 11

Hereditary non-polyposis colorectal carcinoma (Lynch syndrome) is among the most common hereditary cancers in man and a model of cancers arising through deficient DNA mismatch repair (MMR). Lynch syndrome patients are predisposed to different cancers in a non-random fashion, the basis of which is poorly understood. We addressed this issue by determining the molecular profiles for different tumors from a nationwide cohort of Lynch syndrome families (approximately 150 tumors in total). We focused on some less prevalent cancers, affecting the brain (n = 7) and urinary tract (five bladder and five ureter uroepithelial cancers and four kidney adenocarcinomas), and compared their molecular characteristics to those of the most common cancers, colorectal, gastric and endometrial adenocarcinomas, from the same families. Despite origin from verified MMR gene mutation carriers, the frequency of high-level microsatellite instability in tumors varied between high (100-96% for ureter, stomach and colon), intermediate (63-60% for endometrium and bladder) and low (25-0% for kidney and brain). In contrast to gastrointestinal and endometrial carcinomas, active (nuclear) beta-catenin was rare and KRAS mutations were absent in brain and urological tumors. Compared with other tumors, frequent stabilization of p53 protein characterized urinary tract cancers. Promoter methylation of tumor suppressor genes discriminated the tumors in an organ-specific manner. Our findings suggest that different Lynch syndrome tumors develop along different routes. Uroepithelial cancers of the ureter (and bladder to lesser extent) share many characteristics of MMR deficiency-driven tumorigenesis, whereas brain tumors and kidney adenocarcinomas follow separate pathways.
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PMID:Differential cancer predisposition in Lynch syndrome: insights from molecular analysis of brain and urinary tract tumors. 1855 May 72

Urothelial tumors of the renal pelvis and the ureter do not differ from those of the urinary bladder concerning histopathological phenotypes. However, with respect to tumor biology there are relevant differences between the two tumor locations. The originating tissue (urothelium) of the bladder and of the upper urinary tract varies significantly with respect to developmental origin, morphology and physiological function. Specific pathways of tumorigenesis (e.g. hereditary non-polyposis colorectal cancer, HNPCC) and tumor propagation (seeding) are described for tumors of the upper urinary tract. Clinical epidemiological data indicate specific correlations between the two tumor locations.
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PMID:[Renal pelvic carcinoma: a different urothelial tumor?]. 1979 26


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