A tissue microarray was constructed from paraffin wax-embedded blocks from 95 endometrial carcinomas (EC), previously studied for microsatellite instability, as well as for alterations in PTEN, k-RAS and beta-catenin.
Mutations in MSH6 were less prevalent, and MSH6 mutation carriers presented with colorectal and endometrial cancer at later ages than carriers of mutations in MSH2 or MLH1.
Two series of endometrial cancer and precancer (endometrial intraepithelial neoplasia, as diagnosed by computerized morphometric analysis) tissue samples were studied, one for PTEN mutations by the use of denaturing gradient gel electrophoresis and another for PTEN protein expression by immunohistochemistry.
We hypothesized that in PTEN-mutated endometrial cancers, hyperactive Akt signaling downregulates progesterone receptor B (PRB) transcriptional activity, leading to overall impaired progestin responses.
Furthermore, the mean age at diagnosis of endometrial cancer in Japanese MSH6 mutation carriers (49.2 years) was earlier than previous reports from Western countries (56.5 years).
PTEN, a tumor suppressor commonly mutated (50%) in endometrial carcinoma, is found mutated in endometrioid carcinoma of the ovary, but not in other forms of ovarian cancer.
Archival paraffin embedded tumour from women with endometrial cancer enrolled in NCIC CTG studies: EN5 (stage I/II) and IND 126, 148 and 160 (advanced/recurrent disease) were examined for MSI using BAT25/26 and for PTEN expression using immunohistochemistry.
Prophylactic hysterectomy in HNPCC should be restricted to women in whom abdominal surgery for other reasons is performed and to those with particularly increased risk such as MSH6 mutation carriers and/or women with multiple relatives with endometrial carcinoma.
Sprouty 2 immunohistochemical expression was assessed using 3 different tissue microarrays: one constructed from paraffin blocks of 80 samples of normal endometrium and 2 tissue microarrays containing samples of 157 endometrial carcinoma (1 tissue microarray constructed with 95 endometrial carcinomas previously studied for microsatellite instability and alterations in phosphatase and tensin homolog (PTEN), k-ras, and b-catenin, and 1 tissue microarray containing 62 endometrial carcinoma, which were also subjected to sprouty 2 promoter methylation analysis).
Three different human endometrial cancer cell lines known to have wild-type PTEN (HEC 1-A) or a mutated inactive PTEN protein (RL 95-2 and Ishikawa) were used for these studies.
These data also suggest that location of intragenic PTEN mutations and their coexistence with the CMYC amplification may play a crucial part in the development of various subtypes of endometrial carcinoma, but this preliminary suggestion requires further research.
Several molecular alterations, most commonly PTEN mutations but also K-ras mutations, microsatellite instability, and beta-catenin mutations have been detected in endometrioid endometrial carcinoma (EEC).
Formalin-fixed and paraffin-embedded tissue samples with simple hyperplasia (3), complex hyperplasia (5), atypical complex hyperplasia (7), endometrioid carcinomas G1 (20) and G3 (5), and serous carcinoma (5) were evaluated for the presence of mutations in coding regions of PTEN gene, the most frequently mutated tumor suppressor gene in endometrial carcinoma.
Women who were MSH6 mutation carriers had a 26-fold increased incidence of endometrial cancer (HR = 25.5, 95% CI = 16.8 to 38.7) and a sixfold increased incidence of other cancers associated with Lynch syndrome (HR = 6.0, 95% CI = 3.4 to 10.7).
Recently, a link has been established between hMSH6 mutations and 'atypical' hereditary non-polyposis colon cancer (HNPCC) with an increased incidence of endometrial cancers.
We report the first case of compound heterozygosity for two MSH6 mutations resulting in a nonconservative amino-acid change of a conserved residue and in a premature stop codon in a patient who developed rectal and endometrial cancer at ages 19 and 24 years, respectively, and presented few CALS in a single body segment.