Metaphase comparative genomic hybridization was used to analyze the spectrum of genetic alterations in 141 epithelial ovarian cancers from BRCA1 and BRCA2 mutation carriers, individuals with familial non-BRCA1/2 epithelial ovarian cancer, and women with nonfamilial epithelial ovarian cancer. Multiple genetic alterations were identified in almost all tumors. The high frequency with which some alterations were identified suggests the location of genes that are commonly altered during ovarian tumor development. In multiple chromosome regions, there were significant differences in alteration frequency between the four tumor types suggesting that BRCA1/2 mutation status and a family history of ovarian cancer influences the somatic genetic pathway of ovarian cancer progression. These findings were supported by hierarchical cluster analysis, which identified genetic events that tend to occur together during tumorigenesis and several alterations that were specific to tumors of a particular type. In addition, some genetic alterations were strongly associated with differences in tumor differentiation and disease stage. Taken together, these data provide molecular genetic evidence to support previous findings from histopathological studies, which suggest that clinical features of ovarian and breast tumors differ with respect to BRCA1/2 mutation status and/or cancer family history.
Summary— The distribution of epithelial membrane antigen in human transitional epithelium using immunocytochemical techniques was investigated. In inormal urothelium the antigen is restricted to the luminal surface and superficial cell cytoplasm. During neoplastic progression cytoplasmic staining of intermediate and basal cells is seen. In certain circumstances staining is seen at the interface between the stroma and tumour. The latter appearance correlates with the presence of invasion as assessed by conventional histology and may help to identify early invasion in difficult cases.
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The muscle layers of murine gastric fundus have no interstitial cells of Cajal at the level of the myenteric plexus and only possess intramuscular interstitial cells and this tissue does not generate electric slow waves. The absence of intramuscular interstitial cells in W/W V mutants provides a unique opportunity to study the molecular changes that are associated with the loss of these intercalating cells. The gene expression profile of the gastric fundus of wild type and W/W V mice was assayed by murine microarray analysis displaying a total of 8734 elements. Queried genes from the microarray analysis were confirmed by semi-quantitative reverse transcription-polymerase chain reaction. Twenty-one genes were differentially expressed in wild type and W/W V mice. Eleven transcripts had 2.0–2.5 fold higher mRNA expression in W/W V gastric fundus when compared to wild type tissues. Ten transcripts had 2.1–3.9 fold lower expression in W/W V mutants in comparison with wild type animals. None of these genes have ever been implicated in any bowel motility function. These data provides evidence that several important genes have significantly changed in the murine fundus of W/W V mutants that lack intramuscular interstitial cells of Cajal and have reduced enteric motor neurotransmission.
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