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Query: UMLS:C0476089 (endometrial cancer)
 11,379 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

HNPCC is an autosomal dominantly inherited disorder with proclivity to early onset colorectal cancer in the absence of multiple polyps of the colon. There is a predilection for proximal colonic location (70 per cent) and an excess of synchronous and metachronous colorectal cancers. HNPCC is subdivided into Lynch syndrome I, which is restricted to site-specific colon cancer susceptibility, and Lynch syndrome II, which shows all of the features of Lynch syndrome I, but in addition, patients are at inordinately increased risk for carcinoma of the endometrium, ovary, and other anatomic sites. The frequency of HNPCC is conservatively estimated to be 4 to 6 per cent of the total colorectal cancer burden. Because of the fact that the family history is underreported almost uniformly in medical practice, we believe that the true frequency of this disease may be much greater. Heterogeneity may be extant with respect to tumor association, in that in certain Lynch syndrome II kindreds, carcinoma of the pancreas, kidney, breast, and other anatomic sites may predominate. Knowledge of the natural history of HNPCC predicates surveillance and management strategies. Thus, because of the early onset of and proximal predilection for colorectal cancer, we recommend initiation of colonscopy at age 25 and annually thereafter. We also recommend guaiac testing of the stool at least twice a year. In the case of Lynch syndrome II, in addition to colonscopy, we recommend intensive surveillance for the endometrium, including aspiration biopsies. Other targeted organs, depending on the tumor spectrum in the family, should be given priority attention. Because of an excess of synchronous and metachronous colorectal cancer in HNPCC, subtotal colectomy with ileorectal anastomosis is the treatment of choice for initial colorectal cancer. In women presenting with initial colorectal cancer who have completed their families, consideration should be given to prophylactic hysterectomy and bilateral salpingo-oophorectomy at the time of surgery for colorectal cancer. Needed are biomarkers of acceptable sensitivity and specificity for the genotype, because HNPCC lacks premonitory physical signs. We believe that increased knowledge about colorectal cancer etiology and carcinogenesis can be attained through the study of families prone to the Lynch syndromes.
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PMID:Hereditary nonpolyposis colorectal cancer--Lynch syndromes I and II. 306 37

Increasing recognition of the statistical burden posed by HNPCC (5 to 6 percent of all colorectal cancer) mandates that physicians have a better understanding of the genetics, natural history, and distinction between the hereditary site-specific variant (Lynch syndrome I) and the Cancer Family Syndrome (Lynch syndrome II). The authors report detailed cancer (all sites) family histories on two prototype families with Lynch syndrome I (Family R) and Lynch syndrome II (Family N), which have been under investigation for more than two decades. Emphasis is placed on shared clinicogenetic features; namely, early age of onset of colonic cancer (approximately age 44), multiple primary colonic cancer (24 percent of cases showed metachronous colonic cancer), predominance of proximal colonic cancer location (approximately 65 percent in the proximal colon), and vertical transmission consonant with an autosomal dominantly inherited factor. An increased predilection for extracolonic cancer, particularly endometrial carcinoma, occurs in Lynch syndrome II and is the primary basis for distinction from Lynch syndrome I. Surveillance and management programs must be wholly responsive to these natural history features.
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PMID:Differential diagnosis of hereditary nonpolyposis colorectal cancer (Lynch syndrome I and Lynch syndrome II). 336 37

Hereditary nonpolyposis colorectal cancer (HNPCC, synonyms: cancer family syndrome, Lynch syndrome) is characterized by the occurrence of colorectal cancer and other primary tumors in susceptible family members. Inheritance is autosomal dominant with high penetrance. Endometrial cancer is the most frequent extracolonic malignancy in gene carriers. The criteria for the diagnosis HNPCC include the occurrence of colorectal cancer in three close relatives. However, not only colorectal cancer but also endometrial cancer may indicate HNPCC. We present a family diagnosed as a probable HNPCC kindred after endometrial cancer was observed in four sisters. One of these patients and the father of the four sisters had had colorectal cancer. This kindred illustrates the importance of recording the family history in patients with endometrial cancer.
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PMID:Endometrial cancer in four sisters: report of a kindred with presumed cancer family syndrome. 806 41

Endometrial cancer (EC) shares some environmental or genetic risk factors with colorectal cancer (CRC). It represents a risk factor for CRC. Furthermore, EC is the most frequent extracolonic neoplasm in HNPCC (hereditary nonpolyposis colorectal cancer) and, in this syndrome, it has the same inheritance pattern as CRC. Neoplastic family history and clinical features were evaluated in women with EC in a health care district (Pordenone Province) in Northeastern Italy from 1990 to 1995, to examine the proportion of patients with hereditary cancer and the relation with clinical characteristics of EC. We interviewed 215 patients with EC (average age 61 years, range 35-88) in relation with some risk factors (age, weight, diabetes, menstrual and reproductive pattern, synchronous and metachronous neoplasms) and we obtained their family pedigree. Twenty-nine patients (13.5%) had a CRC family history, 66 (30.7%) showed an aspecific cancer aggregation in their families and more than half (120, 55.8%) had a negative cancer family history. Family pedigrees were consistent with a dominant inherited cancer pattern in 8 patients (3.7%) belonging to the CRC-related family history group. A different pattern of family history distribution emerged in relation with age (< 55 vs. > or = 55, p < 0.001) and body mass index (BMI) (< 26 vs. > or = 26, p = 0.002). Patients with a CRC pedigree were more numerous in the younger group, in the group with lower BMI and in pre-menopausal women.
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PMID:Risk factors for endometrial cancer according to familial susceptibility. 963 90

Hereditary nonpolyposis colorectal cancer (Lynch syndrome) is an autosomal dominant disease caused by mutations in the mismatch repair genes in particular in MLH1, MSH2 and MSH6. The disease is characterized by the development of colorectal, endometrial cancer and several other cancers. There is evidence that the clinical expression of the disease varies from one country to another. This variation might affect not only the application of criteria proposed to identify families but also clinical risk factors reported to predict the outcome of genetic testing. Data on site of the cancer, age at diagnosis and pathology were collected from 155 families with suspected HNPCC known at the Korean and Dutch HNPCC registries. DGGE, SSCP and DNA-sequencing were performed to identify MSH2, MLH1 and MSH6 mutations. A total of 33 Korean and 42 Dutch families met the clinical criteria for HNPCC. Germline mutations in the MMR-genes were found in 23 Korean and 24 Dutch families. In families that met the Amsterdam criteria, and also in those associated with MLH1 mutations, more cancers of the stomach and pancreas were observed in the Korean families than in the Dutch HNPCC families; in relative terms, the incidence of cancers of the endometrium in the Korean families was lower. Multivariate analysis showed that an early age at diagnosis, and the occurrence of pancreatic cancer were independent predictive factors of germline mutations in MLH1, MSH2 and MSH6 in the Korean subset of families.
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PMID:Gene-environment interaction in hereditary nonpolyposis colorectal cancer with implications for diagnosis and genetic testing. 1040 64

A patient who had triple cancer (colon cancer, endometrial cancer, and ovarian cancer) in HNPCC kindred is reported. Her family history revealed the occurrence of colon cancer in her paternal aunt and in two cousins, fulfilling the minimum HNPCC criteria. Microsatellite instability analysis revealed replication error (RER)+ in all cancer lesions at 2 microsatellite loci (D1S191, BAT 40). SSCP analysis suggested germline mutation in exon 2 of the hMSH2 gene. This case showed the importance of complete family-history investigations to identify HNPCC patients. In the near future, definitive diagnosis of HNPCC will be possible on the basis of DNA studies.
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PMID:Microsatellite instability and hMSH2 gene mutation in a triple cancer (colon cancer, endometrial cancer, ovarian cancer) patient in hereditary non-polyposis colorectal cancer (HNPCC) kindred. 1068 Mar 34

Nonsteroidal anti-inflammatory drugs (NSAIDs) exhibit cancer preventive effects and have been shown to induce regression of adenomas in FAP patients. In order to elucidate the probable underlying mechanism, the effect of NSAIDs on mismatch repair related microsatellite instability was investigated. Six colorectal cancer cell lines all but one deficient for human mismatch repair (MMR) genes were examined for microsatellite instability (MSI) prior and after treatment with Aspirin or Sulindac. For rapid in vitro analysis of MSI a microcloning assay was developed by combining Laser microdissection and random (PEP-) PCR prior to specific MSI-PCR. Effects of NSAIDs on cell cycle and apoptosis were systematically investigated by using flow cytometry and cell-sorting. MSI frequency in cells deficient of MMR genes (hMSH2, hMLH1, hMSH6) was markedly reduced after long-term (> 10 weeks) NSAID treatment. This effect was reversible, time- and concentration dependent. However, in the hPMS2 deficient endometrial cancer cell line (HEC-1-A) the MSI phenotype kept unchanged. According to cell sorting, non-apoptotic cells were stable and apoptotic cells were unstable. These results suggest that aspirin/sulindac induces a genetic selection for microsatellite stability in a subset of MMR-deficient cells and may thus provide an effective prophylactic therapy for HNPCC related colorectal carcinomas.
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PMID:[Aspirin suppresses microsatellite instability]. 1071 17

1-5% of all patients presenting with colorectal cancer, have an underlying genetic predisposition with an autosomal dominant of pattern of inheritance. Recently the underlying molecular genetic pathway of this syndrome known as HNPCC (hereditary nonpolyposis colorectal cancer) has been characterized: the predisposition is due to a pathogenic mutation in one of the DNA mismatch-repair genes. Colorectal cancers are the leading characterisitic of the syndrom and are frequently encountered at a young age of onset. However, endometrial cancer, stomach cancer, small bowel cancer, urinary tract cancer and skin cancer among others are also inherent to the syndrome. Based on the identification of the underlying molecular genetic pathway, predictive testing has become an option. Once the family-specific underlying pathogenic mutation in one of the DNA mismatch-repair genes has been identified in a proband, at-risk family members may be offered DNA testing with an unequivocal answer to if or if not they have inherited the increased cancer susceptibility. Multiple facets of family DNA testing require a multidisciplinary approach integrating clinicians, geneticists, psychologists, molecular biologist and pathologists. Mutations are identified in a rate of 50-60% of families complying with the Amsterdam criteria for HNPCC. The incidence of recta cancer in HNPCC has as yet not clearly been defined, due to a lack of unequivocal data. In a retrospective analysis (submitted) rectal cancers were encountered in 30% of the HNPCC patients. Half of the patients affected developed metachronous colon cancers. It is essential to address the issue of prophylactic surgery in HNPCC patients presenting with colorectal cancer: Prospective data is required in order to decide which of the options is more beneficial for the HNPCC patient presenting with his first colorectal primary: subtotal colectomy and ileorectal anastomosis versus restorative proctocolectomy. It is evident that apart from the more clinical data quality of life data must be evaluated in this study.
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PMID:[Hereditary nonpolyposis colorectal carcinoma (HNPCC): surgical aspects]. 1132 7

Sporadic endometrial carcinoma can be divided into two biologically and clinically distinctive subtypes of which one is estrogen-related (type I), the other estrogen-unrelated (type II). Type I carcinomas occur at younger age, express estrogen (ER) and progesterone receptors (PR), are frequently associated with endometrial hyperplasia and show a good prognosis. Type II carcinomas occur at older age, are negative for ER and PR, arise in the background of atrophic endometrium and show poor prognosis. Histologically, endometrioid carcinomas correspond to type I carcinomas whereas serous carcinoma is the prototype of type II carcinomas. Endometrioid and serous carcinomas are significantly different with respect to their molecular changes. Endometrioid carcinomas frequently show microsatellite instability (MIN), PTEN and K-ras mutation but infrequently p53 mutations, loss of p16 expression and her2/neu amplification, respectively. In contrast, serous carcinomas show a high frequency of p53 mutations and often loss of p16 expression whereas MIN and PTEN and K-ras mutations are uncommon. Familial endometrial carcinoma associated with HNPCC occur about two decades earlier than sporadic carcinomas, show endometrioid histology and are frequently MIN positiv due to germline mutations of mismatch repair genes (mostly MLH1 and MSH2). During the progression of endometrioid carcinoma PTEN mutations and MIN are considered early changes since they are present in a high frequency in atypical endometrial hyperplasia whereas p53 mutations, loss of p16 expression and her2/neu amplification are considered late events since they are predominantly found in poorly differentiated tumors. In contrast, p53 mutations are considered an early event in the pathogenesis of serous carcinoma occurring already in its putative precursor endometrial intraepithelial carcinoma (EIC). The future research will focus, besides the discovery of new relevant genes, on the interaction of known genes as well as their clinical relevance.
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PMID:[Dualistic model of molecular pathogenesis in endometrial carcinoma]. 1187 8

COX-2, the isoform of cyclooxygenase inducible by cytokines, mitogens, and growth factors, appears to play an important role in inflammation and carcinogenesis. In the colon, COX-2 overexpression results in cell cycle alterations, and NSAIDs have proven effective in cancer chemoprevention. HNPCC (hereditary nonpolyposis colon cancer) is a clinically defined cancer susceptibility syndrome in which women are also at significantly increased risk for the development of endometrial carcinoma. The purpose of this study was to evaluate expression of COX-2 in benign and malignant endometrium in the context of other cell cycle and proliferation markers, including Ki-67, cyclin D1, and the cyclin-dependent kinase inhibitor, p21. Immunostains with COX-2, Ki-67, cyclin D1, and p21 antibodies were performed on formalin-fixed and paraffin-embedded tissue sections from 40 cases: 10 benign (5 atrophic and 5 proliferative) endometria, 6 hyperplasias (complex without atypia), and 24 endometrioid carcinomas (9 well, 4 moderately, and 11 poorly differentiated). Ki-67 was positive in all proliferative and neoplastic endometria. Cyclin D1 and p21 were both overexpressed in endometrial hyperplasia and endometrioid carcinomas. COX-2 was negative in the nonneoplastic endometrium, stained minimally in the well-differentiated endometrioid carcinomas, and stained most strongly in the moderately and poorly differentiated endometrioid carcinomas. Because cyclin D1 may function as an oncogene, its effects may dominate the usual inhibitory effect of a rising p21. Alternatively, it has been shown that p21 can promote cell cycle function by stabilizing cell cycle complexes. The overexpression of COX-2 in poorly differentiated endometrioid carcinoma and lack of expression in hyperplasia and well-differentiated carcinoma suggests that in this form of cancer, COX-2 may play a role in tumor progression rather than tumor initiation.
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PMID:Expression of COX-2, Ki-67, cyclin D1, and P21 in endometrial endometrioid carcinomas. 1191 24


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