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)

Adenocarcinoma of the endometrium in patients 45 years old or younger accounts for 3-8% of all endometrial cancers diagnosed. Ten women of age = 45 years treated for endometrial cancer stage I in our Clinic of Obstetrics and Gynaecology from December 1979 to December 1988. Two cases were nulliparae, none of the 10 patients had Polycystic ovary syndrome and only was obese. In 80% of these cases the presenting symptom was abnormal vaginal bleeding and one patient had coexisting ovarian neoplasia (endometrioid carcinoma). Atypical endometrial hyperplasia was diagnosed in only one case. None of the patients had metastases or capillary like spaces invasion. Our policy was to treat these patients by hysterectomy (Piver 1 or 2), bilateral salpingo-oophorectomy and selective pelvic lymphadenectomy. One patient received adjuvant postoperative radiation therapy (49.5 Gy). One women was submitted two years later to radical mastectomy for ductal carcinoma of the breast. Endometrial adenocarcinoma in premenopausal women is generally of favourable histotype, at early stage and low grade, with excellent prognosis. The problem of quality of life is therefore of utmost importance. After surgical castration 4 of our patients experienced discomfort and excessive weight gain. The implications of long-term estrogen deprivation in younger patients must be seriously considered against as the change of ovarian conservation of hormonal replacement therapy.
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PMID:[Endometrial adenocarcinoma during the fertile age]. 846 59

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

Intratumoral metabolism and synthesis of estrogens are considered to play very important roles in the pathogenesis and development of various sex steroid-dependent neoplasms including breast and endometrial carcinoma. 17 beta-Hydroxysteroid dehydrogenase (17 beta-HSD) isozymes catalyze the interconversion of estradiol (E(2)) and estrone (E(1)), and thereby serve to modulate the tissue levels of bioactive E(2). 17 beta-HSD type 1 primarily catalyzes the reduction of E(1) to E(2), whereas 17 beta-HSD type 2 primarily catalyzes the oxidation of E(2) to E(1). In the human breast and its disorders, 17 beta-HSD type 1 is expressed in proliferative diseases without atypia, atypical ductal hyperplasia, ductal carcinoma in situ and invasive ductal carcinoma. 17 beta-HSD type 2 is not detected in any of the lesions. In addition, 17 beta-HSD type 1 coexpression is significantly correlated with estrogen receptor status in invasive ductal carcinoma cases. These results indicate that breast carcinoma can effectively convert E(1), produced as a result of in situ aromatization, to E(2), a biologically potent estrogen, and exerts estrogenic actions on tumor cells through the estrogen receptor. On the other hand, in the human endometrium, 17 beta-HSD type 2 is expressed, but not 17 beta-HSD type 1. 17 beta-HSD type 2 is expressed in the secretory phase but not in any proliferative phase in the endometrial mucosa. The enzyme is expressed in 75% of endometrial hyperplasias and 37% of carcinoma cases. In endometrial carcinoma cases, a significant inverse correlation has been detected between 17 beta-HSD type 2 immunoreactivity and age (p < 0.02). These results indicate that oxidation of E(2) to E(1) is dominant in endometrial carcinoma, 17 beta-HSD types 1 and 2 play an important role in the regulation of in situ estrogen production in breast and endometrial carcinoma.
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PMID:17-beta-hydroxysteroid dehydrogenase in human breast and endometrial carcinoma. A new development in intracrinology. 1109 50

The established relationship between tamoxifen and the development of endometrial cancer causes differential diagnostic problems between metastatic and primary uterine neoplasms. A 45-year-old woman underwent modified radical mastectomy because of left-breast cancer. She presented with abnormal vaginal bleeding 6 years later, while still on tamoxifen therapy. The endometrial curettage revealed undifferentiated adenocarcinoma. She underwent total abdominal hysterectomy, bilateral salphingoopherectomy as well as pelvic and periaortic lymphadenectomy. Microscopic examination revealed neoplastic cells which formed sheets and duct-like structures in the endometrium. The pattern was not that of a primary endometrial tumour and an immunohistochemical staining was performed using human breast gross cystic disease fluid protein-15 (GCDFP-15) which was found out to be positive in the tumour cells. A diagnosis of metastatic ductal carcinoma of the breast in the uterus was rendered. Uterine metastasis should be kept in mind in patients with a history of breast cancer who are on tamoxifen therapy.
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PMID:Uterine metastasis from infiltrating ductal carcinoma of breast in a patient receiving tamoxifen. 1496 95

Progression of hormone-responsive cancers is characterized by deregulation of the cell cycle and cytoskeleton signaling. In addition, development of breast and endometrial cancer is influenced by the stimulatory action of estrogen. Up-regulation of dynein light chain 1 (DLC1), a component of cytoskeleton signaling, was recently found to promote tumorigenesis. The purpose of our study was to determine the role that DLC1 up-regulation plays in cell cycle progression. To achieve this goal, we used human breast ductal carcinoma ZR-75 cells overexpressing DLC1 as a model system. We found that ZR-75 cells with up-regulated DLC1 were hypersensitive to estrogen-dependent growth stimulation and that DLC1 had an accelerating effect on the G(1)-S transition and stimulated cyclin-dependent kinase 2 (Cdk2) activity. To better understand the promotion of the G(1)-S transition by DLC1, we sought to identify new DLC1-interacting proteins with roles in cell cycle regulation. Using a modified proteomic strategy, we identified two such DLC1-interacting proteins: Cdk2 and Cip-interacting zinc finger protein 1 (Ciz1). DLC1 was verified to interact with Cdk2 and Ciz1 in vivo. We also showed that down-regulation of DLC1 and Ciz1 reduced both Cdk2 activity and cell cycle progression of breast cancer ZR-75 and MCF-7 and endometrial Ishikawa cancer cells. Further, we showed that overexpression of DLC1 is accompanied by a reduction of nuclear p21(WAF1). These findings suggest that interactions among DLC1, Cdk2, and Ciz1 play a regulatory role in cell cycle progression of cancer cells presumably by influencing the levels of nuclear p21(WAF1).
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PMID:Dynein light chain 1 contributes to cell cycle progression by increasing cyclin-dependent kinase 2 activity in estrogen-stimulated cells. 1674 Jul 35

Diagnosis of synchronous primary cancers in one patient is a relatively rare event. The well-known synchronous primary cancers of women are combined ovarian and endometrial cancers, especially when both are the endometrioid cell type. Although breast cancer and endometrial cancer are two common female malignancies, they often occur during the postmenopausal period. Therefore, the possibility of concomitant breast cancer and endometrial cancer in a younger woman (premenopausal) is often neglected. The reported case is an example of this situation. A 37-year-old woman was diagnosed with synchronous breast invasive ductal carcinoma and endometrial endometrioid adenocarcinoma. Since this condition is rarely reported, the correlated risk factors are worthy of our attention and the strategy for prevention is highlighted.
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PMID:Synchronous breast invasive ductal carcinoma and endometrial endometrioid adenocarcinoma: case report. 2151 30

GATA binding protein 3 is a zinc finger transcription factor with high affinity for urothelial tissue and is a promising immunohistochemical marker in detection of urothelial carcinomas (UC). We studied its usefulness in metastatic high-grade UC. This study was performed on cell blocks (CB) of fine needle aspirates from 25 cases of metastatic high-grade UC in patients with previously resected high-grade UC. Immunohistochemical staining for GATA3, thrombomodulin, uroplakin, cytokeratin 7, and cytokeratin 20 was performed. Twenty-three of 25 cases of metastatic UC expressed GATA3 (92%); positive staining for cytokeratin 7 was present in 23 of 25 cases (92%), 20 of 25 (80%) stained for thrombomodulin, and 13 of 25 (52%) stained for cytokeratin 20. No case expressed uroplakin. Five hundred forty-seven non-urothelial carcinomas, including breast ductal carcinoma (77), hepatocellular carcinoma (100), colonic adenocarcinoma (81), pancreatic adenocarcinoma (28), gastric adenocarcinoma (31), endometrial carcinoma (27), ovarian serous carcinoma (27), lung adenocarcinoma (27), lung squamous cell carcinoma (26), malignant melanoma (27), renal cell carcinoma (48), and prostatic adenocarcinoma (48) in tissue microarrays were also analyzed and were GATA3 negative except for 35 of 77 (45.5%) of GATA3 positive breast ductal carcinoma. GATA3 has high sensitivity and specificity for detection of metastatic UC and thus may play an important role in diagnosing metastatic UC in CB samples.
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PMID:GATA3 expression in metastatic urothelial carcinoma in fine needle aspiration cell blocks: a review of 25 cases. 2457

Ductal carcinoma in situ develops in the milk ducts without invading the surrounding connective tissue. Progression to invasive carcinoma is slow and infrequent and is thus difficult to predict. Screening mammography has increased the number of women diagnosed with early-stage ductal carcinoma in situ. What is the best management strategy for patients whose breast biopsy suggests ductal carcinoma in situ? Is watchful waiting a reasonable option? To answer these questions, we conducted a review of the literature using the standard Prescrire methodology. Surgical resection is usually proposed to women with ductal carcinoma in situ but has not been compared with watchful waiting. Resection does not appear to have a major impact on mortality: trials of screening mammography showed no major reduction in breast cancer mortality, but screening does increase the number of diagnoses of ductal carcinoma in situ and, thus, the number of women who undergo surgery. When ductal carcinoma in situ is diagnosed by biopsy, histological examination of the surgically resected tumour reveals invasive breast cancer in about 13% to 24% of cases. Surgical removal of the tumour is usually proposed to women with ductal carcinoma in situ. Excision may be either localised (lumpectomy) or extensive (mastectomy). We found no randomised trials comparing the two approaches. Lumpectomy is usually proposed when the tumour is small (less than 20 mm) and appears to be amenable to complete excision with acceptable cosmetic results. A follow-up study of nearly 2000 women showed a recurrence rate of about 27% between 8 and 10 years after lumpectomy without further treatment. Mastectomy is usually proposed when the tumour appears to be extensive on mammography, or when complete resection with acceptable cosmetic results does not appear feasible, or when the patient chooses this option. Following mastectomy, the risk of carcinoma is similar to that of the general female population. Mastectomy and lumpectomy can both result in persistent pain, which is severe in about 13% of women. Systematic reviews of data for more than 10 000 women have shown that the following factors are statistically associated with an increased risk of recurrence after lumpectomy: age less than 50 years at diagnosis, tumours larger than 25 mm, high-grade tumours, and comedo-type necrosis. Healthy surgical margins of at least 2 mm are associated with a lower risk of recurrence. The impact of radiation therapy after lumpectomy for ductal carcinoma in situ has been evaluated in four randomised trials including a total of 3925 women. Radiation therapy reduced the risk of recurrence but did not prevent death from breast cancer. Irradiation carries a risk of skin burns and long-term cardiovascular and pulmonary toxicity. It also increases the risk of persistent post-surgical pain. In two randomised placebo-controlled trials of lumpectomy with or without radiation therapy for ductal carcinoma in situ, tamoxifen (an antiestrogen) did not affect either overall or breast cancer mortality, but it reduced the risk of recurrence by about one-quarter. Adverse effects of tamoxifen include venous thrombosis and pulmonary embolism, and endometrial cancer. In practice, women diagnosed with ductal carcinoma in situ have a number of options, none of which seems to have a clearly superior harm-benefit balance. Surgical excision reduces the risk of progression but can lead to persistent pain. Following radical mastectomy, the risk of breast cancer is similar to that of the general population. Lumpectomy is associated with a higher risk of recurrence and thus requires closer monitoring. Radiation therapy reduces the risk of recurrence in high-risk situations but has noteworthy adverse effects. Simple clinical monitoring is a valid option for asymptomatic patients: it carries a risk of progression to invasive cancer but avoids exposing many women to the adverse effects of surgery and radiation therapy.
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PMID:Treatment of ductal carcinoma in situ: an uncertain harm-benefit balance. 2460 Jul 34

Some pancreatic neuroendocrine tumors (P-NETs) are associated with hereditary syndromes. An association between Lynch syndrome (LS) and P-NETs has been suggested, however it has not been confirmed to date. We describe the first case associating LS and P-NETs. Here we report a 65-year-old woman who in the past 20 years presented two colorectal carcinomas (CRC) endometrial carcinoma (EC), infiltrating ductal breast carcinoma, small intestine adenocarcinoma, two non-functioning P-NETs and sebomatricoma. With the exception of one P-NET, all these conditions were associated with LS, as confirmed by immunohistochemistry (IHC) and polymerase chain reaction (PCR). LS is caused by a mutation of a mismatch repair (MMR) gene which leads to a loss of expression of its protein. CRC is the most common tumor, followed by EC. Pancreatic tumors have also been associated with LS. Diagnosis of LS is based on clinical criteria (Amsterdam II and Bethesda) and genetic study (MMR gene mutation). The association between LS and our patient's tumors was confirmed by IHC (loss of expression of proteins MLH1 and its dimer PMS2) and the detection of microsatellite instability (MSI) using PCR.
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PMID:Pancreatic non-functioning neuroendocrine tumor: a new entity genetically related to Lynch syndrome. 2918 99

Conventional cancer drug development has long been limited to organ- or tissue-specific cancer types. However, it has become increasingly known that specific genetic abnormalities are responsible for the carcinogenesis of multiple cancers. The recent US Food and Drug Administration (FDA) approval of the first multi-cancer drug, Keytruda, has demonstrated the feasibility of developing new drugs that target multiple cancers. Despite a promising future, methodological development for identifying multi-cancer molecular targets remains encumbered. This study developed a novel machine learning approach to identify such genes responsible for multiple cancers by synthesizing salient genomic information from cancer-specific classification models. This approach centered on the cross-cancer prediction method for identifying groups of cancers with high cross-cancer predictability. Furthermore, a robust hybrid classifier, comprising Prediction Analysis for Microarrays and Random Forest, was developed to integrate predictive models for gene inference. This approach has successfully identified key genes shared by endometrial cancer, mammary gland ductal carcinoma, and small cell lung cancer. The results are supported by published experimental evidence. This framework holds potential to transform the current methods of discovering multi-cancer molecular targets for clinical oncology.
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PMID:Cross-cancer Prediction: A Novel Machine Learning Approach to Discover Molecular Targets for Development of Treatments for Multiple Cancers. 3036 84


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