Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0476089 (endometrial cancer)
 11,379 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Cowden's disease, or multiple hamartoma syndrome, is a rare condition classified recently as a hereditary preneoplastic syndrome. Multiple orocutaneous hamartomas are associated with involvement of other organ systems, including fibrocystic breast disease and breast carcinoma, goiter, thyroid cancer, gastrointestinal polyps, and endometrial carcinoma. We describe a patient with Cowden's disease who underwent extensive gastroenterological work-up and review other cases in the literature.
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PMID:Cowden's disease with extensive gastrointestinal polyposis. 811 85

We report a case of invasive breast cancer in a 62-year-old female patient with Cowden's disease. A left modified radical mastectomy was performed and histopathology of the tumor showed invasive ductal carcinoma, histological grade 3, without lymph node metastasis. The patient had a past history of endometrial cancer at 55 but did not have a family history of malignant disease. Goiter was palpable but aspiration cytology revealed no malignancy. There were several papillomas on the oral mucosa and multiple papillomatous lesions on the right femur. Barium X-ray and endoscopic examination revealed multiple, small, hyperplastic polypoid lesions on the esophagus, stomach and rectum. Histopathology of the biopsy specimens from the esophagus and stomach showed acanthotic squamous epithelium and foveolar hyperplastic polyps. The patient was followed up closely to monitor the thyroid lesions and polyposis of the digestive tract. A total of 12 breast cancer patients who also had Cowden's disease have been reported in Japan and these cases are reviewed in this report.
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PMID:Breast cancer in Cowden's disease: a case report with review of the literature. 949 Nov 41

About 13% of all colorectal cancer may be dominantly inherited. This amounts to about 300 new cases a year in Norway. Colorectal cancer can be cured by early diagnosis and treatment. Coloscopy with polypectomy may prevent infiltrating cancer. Affected families should be offered genetic evaluation, and family members subjected to regular colonoscopy. The genetic bases of five colorectal cancer syndromes, accounting for most cases of hereditary early onset colorectal cancer, have now been determined. These are familial adenomatous polyposis, colon-endometrial cancer (hereditary non-polyposis colon cancer), Cowden's syndrome, Peutz-Jegher's syndrome and juvenile polyposis. These account for at most 3% of all colorectal cancers. In this group, predictive genetic testing may be employed in families with known mutation. Demonstration of mutation carriers by predictive testing must be based on health service available to the persons at risk. With regard to prophylactic measures, experimental and epidemiological data suggest a preventive effect of aspirin and resistant starch. Empirical information on the effect of intervention is insufficient; multicentre studies are needed.
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PMID:[Hereditary colorectal cancer]. 1059 56

PTEN is one of the most commonly mutated tumor suppressor genes in human cancer. PTEN mutations have been implicated in the development of a variety of human neoplasia, including high-grade glioblastoma, prostate, breast, endometrial, and thyroid carcinoma. Germ-line mutations of PTEN cause Cowden's syndrome (CS), a multiple hamartoma condition resulting in increased susceptibility for the development of cancer. When more than 6 months old, pten+/- mice develop a range of tumors, partially resembling the spectrum of neoplasia observed in CS patients. One-half (32 of 65) of pten+/- females developed breast tumors, whereas all (65 of 65) of the females had endometrial hyperplasia, and there was a high incidence (14 of 65) of endometrial cancer. Hamartoamous tumors of the gastrointestinal tract, as well as prostate and adrenal neoplasia, were also frequently observed. Significantly, the spectrum of neoplasia observed in pten+/- mice partially overlaps with the types of tumors frequently detected in CS patients. The majority of tumors in pten+/- mice exhibit loss of heterozygosity at the pten locus, which indicates the importance for loss of PTEN function in tumor formation. Consistent with the role of PTEN in negative regulation of PKB/Akt phosphorylation and activity, pten loss of heterozygosity is accompanied by hyperphosphorylation of PKB/Akt in tumors. Taken together, our results establish pten+/- mice as an excellent animal model system for the investigation of PTEN-related hamartoma syndromes, as well as the role of PTEN in breast and endometrial carcinogenesis.
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PMID:High incidence of breast and endometrial neoplasia resembling human Cowden syndrome in pten+/- mice. 1091 75

Cowden syndrome is an autosomal dominant genodermatosis, characterized by the presence of multiple hamartomas in the skin, breast, thyroid, gastrointestinal tract, central nervous system, and an increased risk in developing breast and thyroid carcinomas. Over 80 germline mutations of the tumor suppressor gene PTEN, on chromosome 10q23, have been reported in more than 100 unrelated patients and families; however, questions regarding distribution of the mutations in populations from different geographic areas, and phenotypic expression are still unclear. In this study the results are reported of mutation analysis of PTEN in 13 families from Spain and one family of Brazilian origin with Cowden syndrome. PTEN germline mutations were detected in nine of them (64%). Five mutations were located in exon 5, one in exon 6, two in exon 7, and one in exon 8. Four of the mutations were novel. In another case, an identical change had been previously reported as a somatic mutation in an endometrial carcinoma. In one family, the patient presented a de novo mutation, which was not detected in his parents. In five patients, the detection of the PTEN germline mutation confirmed their condition, even in the absence of sufficient criteria to make the clinical diagnosis of Cowden syndrome.
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PMID:PTEN mutations in eight Spanish families and one Brazilian family with Cowden syndrome. 1191 10

Not since the discovery of p53 has another molecule received as much attention as PTEN. In the 5 years since the discovery of PTEN, encoding a dual specificity phosphatase tumor suppressor on 10q23, it has been shown to be a susceptibility gene for an inherited cancer syndrome, Cowden syndrome, and for several developmental disorders; it has been shown to play a prominent role in normal murine and human development; and it has been shown to be instrumental in cell cycle arrest, apoptosis, and/or possibly cell migration and cytoskeletal affairs. Initial work on cancer cell lines had suggested that PTEN caused every type of cancer because it was reported that a relatively high frequency of a variety of cancer cell lines, whether derived from solid tumors or hematological malignancies, had homozygous or compound heterozygous genetic alterations involving PTEN. Such data, together with the germ-line human and murine model data, suggested that PTEN mutations occurred "early" in sporadic tumorigenesis. However, subsequent painstaking work in noncultured primary tumors and in careful in vitro overexpression studies over the last 4 years demonstrated that the mechanism of PTEN inactivation can be varied and might be cell type dependent. Furthermore, apart from sporadic endometrial carcinoma, PTEN alteration in noncultured sporadic neoplasias likely occurs "late," promoting progression and metastasis. The article by Davies et al. (Clin Cancer Res., 8: 1904-1914, 2002) sheds light on all of these issues when they report on data that derive from a "triple threat" strategy, i.e., in vitro, in vivo, and ex vivo, to demonstrate that adenoviral infection of PTEN into PTEN-null PC3 prostate cancer cell lines results in decreased metastatic potential without significantly altering tumor size via the predominant mechanism of G(1) cell cycle arrest but not apoptosis.
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PMID:The expanding role of PTEN in neoplasia: a molecule for all seasons? Commentary re: M. A. Davies, et al., Adenoviral-mediated expression of MMAC/PTEN inhibits proliferation and metastasis of human prostate cancer cells. Clin. Cancer Res., 8: 1904-1914, 2002. 1206 Jun 35

PTEN on 10q23.3 encodes a dual-specificity phosphatase that negatively regulates the phosphoinositol-3-kinase/Akt pathway and mediates cell-cycle arrest and apoptosis. Germline PTEN mutations cause Cowden syndrome and a range of several different hamartoma-tumor syndromes. Hereditary nonpolyposis colon cancer (HNPCC) syndrome is characterized by germline mutations in the mismatch repair (MMR) genes and by microsatellite instability (MSI) in component tumors. Although both colorectal carcinoma and endometrial carcinoma are the most frequent component cancers in HNPCC, only endometrial cancer has been shown to be a minor component of Cowden syndrome. We have demonstrated that somatic inactivation of PTEN is involved in both sporadic endometrial cancers and HNPCC-related endometrial cancers but with different mutational spectra and different relationships to MSI. In the current study, we sought to determine the relationship of PTEN mutation, 10q23 loss of heterozygosity, PTEN expression, and MSI status in colorectal cancers (CRCs). Among 11 HNPCC CRCs, 32 MSI+ sporadic cancers, and 39 MSI- tumors, loss of heterozygosity at 10q23.3 was found in 0%, 8%, and 19%, respectively. Somatic mutations were found in 18% (2 of 11) of the HNPCC CRCs and 13% (4 of 32) of the MSI+ sporadic tumors, but not in MSI- cancers (P = 0.015). All somatic mutations occurred in the two 6(A) coding mononucleotide tracts in PTEN, suggestive of the etiological role of the deficient MMR. Immunohistochemical analysis revealed 31% (14 of 45) of the HNPCC CRCs and 41% (9 of 22) of the MSI+ sporadic tumors with absent or depressed PTEN expression. Approximately 17% (4 of 23) of the MSI- CRCs had decreased PTEN expression, and no MSI- tumor had complete loss of PTEN expression. Among the five HNPCC or MSI+ sporadic CRCs carrying frameshift somatic mutations with immunohistochemistry data, three had lost all PTEN expression, one showed weak PTEN expression levels, and one had mixed tumor cell populations with weak and moderate expression levels. These results suggest that PTEN frameshift mutations in HNPCC and sporadic MSI+ tumors are a consequence of mismatch repair deficiency. Further, hemizygous deletions in MSI- CRCs lead to loss or reduction of PTEN protein levels and contribute to tumor progression. Finally, our data also suggest that epigenetic inactivation of PTEN, including differential subcellular compartmentalization, occurs in CRCs.
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PMID:PTEN mutational spectra, expression levels, and subcellular localization in microsatellite stable and unstable colorectal cancers. 1216 69

Germline mutations in the tumor-suppressor gene PTEN (MMAC1, TEP1) are found in Cowden syndrome, which predisposes to hamartomas, breast cancer, trichilemmomas, and thyroid tumors of follicular epithelium. PTEN has also been found to be somatically deleted, mutated, and/or silenced in various sporadically occurring cancers such as glioblastoma, breast cancer, kidney cancer, malignant melanoma, and endometrial cancer. Loss or reduction of PTEN protein expression as well as inappropriate subcellular compartmentalization is seen in non-medullary thyroid cancers. However, although allelic loss of the PTEN locus in 10q23.3 is frequently seen, this is not coupled with mutations in the PTEN gene. To approach further the frequency and mechanism behind PTEN silencing, we screened a panel of 87 sporadic thyroid tumors for PTEN mRNA expression, including 14 anaplastic carcinomas, 37 follicular carcinomas, 21 atypical adenomas, and 15 ordinary adenomas. Complete loss of PTEN mRNA expression was evident in six of the tumors, including four anaplastic carcinomas, one widely invasive carcinoma, and one ordinary adenoma. The transcriptional silencing of PTEN was significantly associated with the anaplastic subtype, suggesting that PTEN is involved in the carcinogenesis of highly malignant or late-stage thyroid cancers, whereas this particular mechanism appears to be of minor importance in differentiated follicular thyroid tumors. No association was observed between the expression, loss of heterozygosity, and mutation status in the 33 cases in which these parameters were compared. This indicates that PTEN silencing is a result of a wide variety of epigenetic and/or structural silencing mechanisms rather than a consequence of structural biallelic inactivation of the classical type. Furthermore, the high rate of alterations in the 10q23 region might indicate the presence of an as-yet unknown tumor-suppressor gene with an important role in the development of thyroid tumors.
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PMID:Silencing of the PTEN tumor-suppressor gene in anaplastic thyroid cancer. 1220 92

The inherited hamartoma polyposis syndromes encompass several distinct clinical syndromes with different genetic bases, Cowden syndrome (CS), Bannayan-Riley-Ruvalcaba syndrome (BRRS), juvenile polyposis syndrome (JPS), and Peutz-Jeghers syndrome (PJS). Germline mutations in PTEN, encoding a tumor suppressor phosphatase on 10q23.3, is associated with 80% of CS and 60% of BRRS. JPS is caused by mutations in MADH4 and BMPR1A, encoding two members of the TGFB superfamily. Germline mutations in LKB1 (STK11) are associated with a subset of PJS. The number, distribution, and histologic type of polyps differ amongst these syndromes as do component cancer risks. While rare, usually asymptomatic, hamartomatous polyps are felt to be component to CS. Hamartomatous polyposis is usually prominent and symptomatic in BRRS. Polyposis, which can be quite symptomatic, is a cardinal component feature of PJS and JPS. Interestingly, glycogenic acanthosis of the esophagus is highly predictive of CS and the presence of PTEN mutation. PTEN mutation positive CS have been shown to be at increased risk of breast, thyroid, and endometrial cancer. PTEN mutation positive BRRS are at increased risk of at least breast cancer, possibly that of the thyroid as well. In contrast, JPS and PJS have increased risk of gastrointestinal cancers in particular. Thus, molecular-based diagnoses to differentiate each of these syndromes are important for medical management.
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PMID:Constipation, polyps, or cancer? Let PTEN predict your future. 1451 69

New insights into the genetic basis of carcinogenesis have been obtained by modern molecular biological techniques. Several susceptibility genes are known. The hereditary breast and ovarian cancer syndrome (germline mutations in BRCA1 and BRCA2) and endometrial cancer in the context of the hereditary non-polyposis colorectal cancer syndrome (HNPCC), germline mutations in mismatch-repair genes, are the most frequent hereditary cancer syndromes in gynaecology. Mutations in TP53 (Li-Fraumeni syndrome) and PTEN (Cowden's disease), associated with increased risk of breast cancer, are responsible for a smaller portion of familial breast cancer. The risk of inheritance and disease can be identified and defined by investigating family history, risk calculation programs, and genetic testing. Afterwards, options of primary, secondary, and tertiary prevention can be formulated. Presently, prophylactic surgery is the only option proven by clinical trials that can reduce the mortality of hereditary breast and ovarian cancer.
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PMID:[Prophylactic surgery of mammary and ovarian carcinoma]. 1623 64


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