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

Endometrial cancer is increasingly common in affluent Western countries, largely owing to the growing obesity of those populations. There are two recognized types of endometrial cancer: Type I is more common and is associated with obese postmenopausal women and comprises approximately 80% of all endometrial cancers; Type II describes a woman who is often younger and thinner with a more aggressive histologic type that is nonestrogen dependent, of either serous or clear cell histology, and consists of a more aggressive clinical course and results in poorer prognosis. As the majority of patients with endometrial cancer present with symptoms and have early disease, screening is unlikely to be cost effective or reduce the mortality rate. However, surveillance of high-risk populations is a different proposition. Patients who may benefit from routine surveillance include those with a family history of endometrial cancer, a history of hormone replacement therapy with less than 12-14 days of progestogens, long-term use of tamoxifen, hereditary nonpolyposis colorectal cancer family syndrome, Cowden's syndrome, Peutz-Jeghers syndrome, a history of breast cancer and obesity. Most patients with endometrial cancer are offered surgery as first-line therapy. The standard surgical procedure should be an extrafascial total hysterectomy with bilateral salpingo-oophorectomy. Adnexal removal is also recommended, even if the adnexa appear normal, as they may contain micrometastases. The safety of a laparoscopic approach in the surgical management of uterine cancer has not yet been demonstrated in prospective randomized trials, therefore, the field awaits the Gynaecologic Oncology Group's prospective Lap-2 study. While post-treatment follow-up guidelines vary between institutions and countries, in general, patients at high risk of recurrence are followed closely every 3-4 months for the first year or two, then every 6 months to complete 5 years of follow-up.
 ...
PMID:An overview of uterine cancer and its management. 1637 42

Germline mutations of PTEN (phosphatase and tensin homolog deleted on chromosome 10) are associated with the multihamartomatous disorder Cowden syndrome (CS). Moreover, patients with CS with germline PTEN promoter mutations have aberrant PTEN protein expression and an increased frequency of breast cancer. Here, we examined the downstream effect of five PTEN promoter variants (-861G/T, -853C/G, -834C/T, -798G/C, and -764G/A) that are not within any known cis-acting regulatory elements. Clinically, all five of these patients have been given diagnoses of breast, thyroid, and/or endometrial cancer. We demonstrated that protein binding to the PTEN promoter (-893 to -755) was not altered in the five variants when compared with the wild-type (WT) promoter. However, reporter assays indicated that three of the variants (-861G/T, -853C/G, and -764G/A) demonstrated an ~50% decrease in luciferase activity compared with the WT construct. PTEN messenger RNA (mRNA) levels were not altered in these variants, whereas secondary structure predictions indicated that different PTEN 5' untranslated region transcript-folding patterns exist in three variants, suggesting an inhibition of protein translation. This was confirmed by PTEN protein analysis. These data indicate that variants causing large mRNA secondary structure alterations result in an inhibition of protein translation and a decrease in PTEN protein expression. These data emphasize the importance of PTEN promoter nucleotide variations and their ability to lead to CS progression by a novel regulatory mechanism. Importantly, these patients have a high prevalence of breast, thyroid, and endometrial malignancies; thus, understanding of the mechanism of PTEN dysfunction in these patients will lead to more-sensitive molecular diagnostic and predictive testing and, ultimately, to rational targeted therapies to treat or prevent malignancy.
 ...
PMID:Cowden syndrome-affected patients with PTEN promoter mutations demonstrate abnormal protein translation. 1784

The PTEN hamartoma tumor syndromes (PHTS) are a collection of rare clinical syndromes characterized by germline mutations of the tumor suppressor PTEN. These syndromes are driven by cellular overgrowth, leading to benign hamartomas in virtually any organ. Cowden syndrome (CS), the prototypic PHTS syndrome, is associated with increased susceptibility to breast, thyroid, and endometrial cancer. PTEN is located on chromosome 10q22-23 and negatively regulates the prosurvival PI3K/Akt/mTOR pathway through its lipid phosphatase activity. Loss of PTEN activates this pathway and leads to increased cellular growth, migration, proliferation, and survival. Clinical management of patients with PHTS, particularly those with CS, should include early and frequent screening, surveillance, and preventive care for associated malignancies. Concomitant with improved understanding of the biology of PTEN and the PI3K/Akt/mTOR pathway, inhibitors of this pathway are being developed as anticancer agents. These medications could have applications for patients with PHTS, for whom no medical options currently exist.
 ...
PMID:PTEN hamartoma tumor syndromes. 1878 Nov 91

Cowden syndrome (multiple hamartoma syndrome, MIM 158350) is an early onset syndrome characterized by multiple hamartomas in the skin, mucous membranes, breast, thyroid and endometrium. Patients with Cowden syndrome have increased risk of breast cancer, thyroid cancer and endometrial cancer. In 1997 germline mutations in PTEN were demonstrated to cause Cowden syndrome. We report the results of diagnostic and predictive testing in all families with Cowden syndrome or suspected Cowden syndrome registered at the Norwegian cancer family clinics. PTEN mutations were found in all six families meeting the clinical criteria for Cowden syndrome, in none of the two families assumed to have Cowden syndrome but not fulfilling the criteria, and in none of the eight families selected in our computerized medical files to have a combination of breast and thyroid cancers. Age-related penetrances for the various neoplasms are given. All families but one were small and de novo mutations were found.
 ...
PMID:Germline PTEN mutations are rare and highly penetrant. 2022 21

Cowden syndrome (CS) is the prototypic PTEN hamartoma tumor syndromes (PHTS), rare clinical syndromes characterized by germline mutations of the tumor suppressor PTEN. CS is characterized by association of macrocephaly, facial trichilemmomas, acral keratoses, papillomatous papules, with increased risk for breast, thyroid and endometrial cancer. PTEN, which is located on chromosome 10q23, regulates negatively the prosurvival PI3K/Akt/mTOR pathway through a lipid phosphatase activity. Loss of PTEN activates this pathway and leads to increased cellular growth, migration, proliferation, and survival. CS diagnosis is clinical, based on the association of pathognomonic, major and minor criteria. The association in a patient with thyroid cancer, rarely with multinodular goiter, of typical dermatological manifestations, easily identifiable by clinical examination (papillomatous papules, acral keratoses, trichilemmomas), with a history of breast, endometrial, or renal cancer, or hamartomatous tumors presence, should alert the clinician. Clinical management of patients with CS is multidisciplinary, to include early and frequent screening, surveillance, and preventive care for associated malignancies. The development of antineoplastic agents targeting PI3K/Akt/mTOR pathway, such as rapamycin, may be the opportunity of treatment in PHTS and CS patients, for whom no specific medical treatment exist.
 ...
PMID:[Cowden syndrome, or multiple hamartomatous tumor syndrome, in clinical endocrinology]. 2062 33

Cowden syndrome (CS) is a cancer predisposition syndrome caused by germline mutations in the PTEN tumor suppressor gene. It is associated with an increased risk of thyroid, breast and endometrial cancer but many manifestations can be found in the head and neck region, some of which are pathognomonic. Here we report a 35-year-old male referred by his dentist for evaluation of a lesion located near the retromolar trigone. Comprehensive clinical examination revealed papillomatous skin lesions, macrocephaly and gingival hypertrophy. Histopathological examination of the lesion showed an acinic cell carcinoma (ACC) of minor salivary gland origin. Analysis of the PTEN gene identified a germline R130Q mutation in exon 5, confirming the diagnosis of CS, but no loss of heterozygosity was seen in DNA extracted from tumor tissue. This is to our knowledge the first case describing an association of ACC of the minor salivary gland with a PTEN-gene related disorder. It emphasizes the importance of head and neck examination in these patients.
 ...
PMID:Acinic cell carcinoma of the retromolar trigone region: expanding the tumor phenotype in Cowden syndrome? 2182 20

Cowden syndrome is a rare autosomal dominant disorder that is characterized by multiple hamartomas in a variety of tissues and this is associated with germline mutations in the phosphatase and tensin homologue (PTEN) gene, which is the tumor suppressor gene located on chromosome 10q23.3. It is characterized by multiple hamartomatous neoplasms of the skin, oral mucosa, gastrointestinal (GI) tract, bones, central nervous system, eyes, and genitourinary tract. Cowden syndrome does not have increased risk of GI malignancy; however, it has an increased risk of breast, thyroid and endometrial cancer development. Here the authors report a rare case of Cowden syndrome incidentally diagnosed from multiple gastric polyposis. A 29-year-old woman presented with multiple gastric polyps. The laboratory results were normal except for mild anemia, with a hemoglobin level of 11.9 g/dL. Esophagogastroduodenoscopy revealed multiple gastric, duodenal polyps and esophageal acanthosis. Colonoscopy revealed possible hamartomatous polyps in the rectum. Under the suspicion of Cowden syndrome, sonography of the thyroid and breasts was carried out, which revealed multiple thyroid masses. Subsequent fine-needle aspiration biopsy revealed the presence of clusters of follicular epithelial cells, and due to the possibility of malignancy, the patient underwent total thyroidectomy. The pathology was reported as invasive follicular carcinoma. A gene study by direct sequencing showed the presence of a PTEN mutation (c.633C > A /p.Cys211*).
 ...
PMID:A case of Cowden syndrome diagnosed from multiple gastric polyposis. 2237 48

A 27-year-old female patient presented with multiple lipomas and cavernous hemangiomas of the skin, hemangioma of the parotid gland, polyps of the gastrointestinal tract and endometrial carcinoma. After 1 year the patient presented with papillary thyroid carcinoma and a diagnosis of Cowden syndrome (CS) was made. Genetic testing revealed a pathogenic PTEN gene mutation. Hereditary tumor syndromes, such as CS are underdiagnosed. Clinical management can be adjusted to the needs of CS patients only if an early diagnosis is made. In CS the risk for thyroid, breast and endometrial cancer is severely increased.
 ...
PMID:[Multiple hemangiomas, polyposis coli, endometrial and papillary thyroid cancer]. 2238 23

This review article discusses hereditary cancer predisposition syndromes with uterine manifestations. Lynch syndrome accounts for 2% to 3% of endometrial cancers. The identification of endometrial cancer patients at risk for Lynch syndrome is discussed, as are the characteristics of Lynch syndrome-associated endometrial cancer and the screening and prevention options for women at risk for Lynch syndrome-associated endometrial cancer. Endometrial cancer associated with PTEN hamartoma tumor syndrome (also known as Cowden syndrome) is also discussed. HLRCC (hereditary leiomyomatosis and renal cell carcinoma), which has an associated high risk of symptomatic uterine leiomyomas, is reviewed.
 ...
PMID:Genetic testing by cancer site: uterus. 2284 35

In the last two decades there have been significant advances in our understanding of female genital tract tumours. The discovery of BRCA1 and BRCA2 genes in ovarian cancer and the mismatch repair genes in endometrial carcinoma has revolutionized our approach to the diagnosis and screening of women for ovarian and uterine cancers. This review discusses the pathogenesis of these two hereditary syndromes in depth and explains how the molecular genetics is tailoring the manner in which these diseases are diagnosed and potentially treated. Other, less common hereditary conditions associated with gynaecological tract manifestations, such as Cowden syndrome, Peutz-Jeghers syndrome, Gorlin syndrome and hereditary leiomyomatosis and renal cell carcinoma, are also summarized briefly.
 ...
PMID:Hereditary gynaecological malignancies: advances in screening and treatment. 2324 Jun 67


<< Previous 1 2 3 4 Next >>