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

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

Lynch syndrome is a peculiar disease, accounting for 5% of the total burden of colon cancer. Characteristics of this disease are autosomal dominant transmission, early onset, and frequent right colon localization. Diagnostic criteria, aimed to collaborative studies, are based on these features (so called Amsterdam criteria). Lynch syndrome has specific biomolecular features (microsatellite instability); mismatch repair genes have been identified as responsible of this syndrome. Lynch syndrome causes high risk for extracolonic malignancies, particularly for endometrial cancer, supposed to be related to mutation of hMSH2 gene. Another feature of Lynch syndrome tumours is better survival with respect to sporadic counterpart. Genetic test allows identifying the state of mutation carriers and selects the patients to submit to screening. Endoscopic screening has been demonstrated to reduce incidence of colorectal malignancies in this syndrome.
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PMID:[The Lynch syndrome]. 1068 68

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

The first description of hereditary non polyposis colorectal cancer goes back to Warthin's study in 1895. In 1966 two families with autosomal dominant predisposition to colon and endometrial cancer were found. This condition was defined initially as familial neoplasm syndrome, then Lynch syndrome, and at last hereditary non polyposis colorectal cancer (HNPCC). HNPCC is classically subdivided into Lynch syndrome I (characterized by predisposition to colorectal cancer with early age of onset, to cancer of the proximal colon, and excess of synchronous and metachronous cancer), and Lynch syndrome II (characterized by similar colic phenotype with augmented risk of extracolonic neoplasm). If all clinical characteristics are present, it is possible to suspect HNPCC: however, diagnosis is difficult. Histological and genetic features of colon cancer confirm the diagnosis of HNPCC. Surgical therapy of colic neoplasm is total colectomy. A careful screening of HNPCC family members is one of the cardinal point in prevention. Follow-up of these surgical patients is the same as for sporadic neoplasms.
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PMID:[Hereditary non polyposis colorectal cancer (HNPCC). A clinical and genetic entity]. 1183 61

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

HNPCC is an autosomal dominantly inherited cancer-susceptibility syndrome that confers an increased risk for colorectal cancer and endometrial cancer at a young age. It also entails an increased risk of a variety of other tumors, such as ovarian, gastric, uroepithelial and biliary tract cancers. The underlying pathogenic mutation lies in 1 of the 5 known DNA MMR genes (MSH2, MLH1, PMS1, PMS2 and MSH6). We screened a total of 140 individuals from 56 Spanish families with suspected HNPCC for mutations in the DNA mismatch repair genes MLH1 and MSH2, using DGGE and direct DNA sequencing. Families were selected on the basis of a history of HNPCC-related tumors or the occurrence of other associated tumors in members besides the index case affected with colorectal cancer. We detected 14 definite pathogenic germline mutations, 9 in MLH1 and 5 in MSH2 in 13 unrelated families selected by the Amsterdam criteria and Bethesda guidelines (1 family carries 2 mutations) and 3 missense mutations in 3 unrelated families selected by the Amsterdam criteria. Among the 17 germline mutations noted in the Spanish cohort, 10 are novel, 7 in MLH1 and 3 in MSH2, perhaps demonstrating different mutational spectra in the Spanish population, where no founder mutation has been identified. Based on our results, we suggest that in the Spanish population not only HNPCC families fulfilling the Amsterdam criteria but also those following Bethesda guidelines should undergo genetic testing for MSH2 and MLH1 mutations.
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PMID:Prevalence of germline mutations of MLH1 and MSH2 in hereditary nonpolyposis colorectal cancer families from Spain. 1192 Jun 50

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

Due to major developments in genetics over the past decade, molecular biology tests are serving promising tools in early diagnosis and follow-up of cancer patients. Recent epidemiological studies revealed that the risk for each individual to develop cancer is closely linked to his/her own genetic potentialities. Some populations that are defective in DNA repair processes, for example in Xeroderma pigmentosum or in the Lynch syndrome, are particularly prone to cancer due to the accumulation of mutations within the genome. Such populations would benefit from the development of tests aimed at identifying people who are particularly at risk. Here, we review some data suggesting that the inactivation of mismatch repair is often found in endometrial cancer and we discuss molecular-based strategies that would help to identify the affected individuals in families with cases of glandular malignancies.
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PMID:Mismatch repair genes and microsatellite instability as molecular markers for gynecological cancer detection. 1219 99


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