2008 Summer Meeting - Leeds - The Pathological Society of Great ...
2008 Summer Meeting - Leeds - The Pathological Society of Great ...
2008 Summer Meeting - Leeds - The Pathological Society of Great ...
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O17Regulation <strong>of</strong> the Adenomatous Polyposis Coli gene by themiR-135 family in colorectal cancerB Diosdado 1 , R Nagel 2 , C Le Sage 2 , M Van Der Waal 2 ,JAF Oude Vrielink 2 , A Bolijn 1 , GA Meijer 1 ,RAgami 21 Department <strong>of</strong> Pathology, VUmc University Medical Centre, Amsterdam,the Netherlands, 2 Division <strong>of</strong> Tumour Biology, <strong>The</strong> Netherlands CancerInstitute, Amsterdam, the NetherlandsBackground: <strong>The</strong> canonical Wnt pathway maintains the proliferativecompartment at the crypts <strong>of</strong> the intestine and cell fate and position <strong>of</strong> theepithelial cells. Inactivation <strong>of</strong> the tumour suppressor gene AdenomatousPolyposis Coli (APC), a key component <strong>of</strong> the Wnt pathway, causes formation<strong>of</strong> adenomas. MicroRNAs (miRNAs) are non-coding RNAs which silence theexpression <strong>of</strong> their target genes. MiRNAs act as oncogenes and tumoursuppressors by regulating the expression <strong>of</strong> genes involved in centralmechanisms <strong>of</strong> tumorigenesis.Aim: To determine miRNAs involved in CRC initiation by elucidatingmiRNAs regulating the Wnt pathway.Methods: A miRNA expression library was used to identify miRNAs regulatingthe APC gene. Functional relevance <strong>of</strong> the APC-miRNA interactions wasassessed using TOPFLASH reporters and transcriptional induction <strong>of</strong> c-myc.Expression <strong>of</strong> the APC gene and the miRNAs was measured by qRT-PCR in 20adenocarcinomas, 23 adenomas and 18 controls.Results: We showed that miR-135a&b target the 3’UTR <strong>of</strong> APC, suppress itsexpression and induce Wnt pathway activity. We found significant upregulation<strong>of</strong> miR-135a&b from controls, through adenomas toadenocarcinomas, which is correlated with decreasing expression <strong>of</strong> APC.Conclusion: Our results uncovered a miRNA-mediated mechanism for thecontrol <strong>of</strong> the Wnt pathway activity and suggest its contribution to CRCpathogenesis.O19Changes in Autopsy Practice Following Cardiac Surgery Over17 YearsMF Alikhan 1 , PJ Gallagher 1 , DE Pontefract 11 Department <strong>of</strong> Pathology, Southampton University Hospitals,Southampton UKBACKGROUND: <strong>The</strong>re has been a decline in general autopsy frequency andthe use <strong>of</strong> histology in recent years. Previous studies at our centre havedemonstrated a constant autopsy rate (86-88%) but declining use <strong>of</strong> histologyafter cardiac surgery.AIMS: To assess changes in the autopsy rate, use <strong>of</strong> histology and cause <strong>of</strong>death following adult cardiac surgery in a UK teaching hospital.METHODS/RESULTS: A retrospective analysis <strong>of</strong> the local cardiac surgerydatabase identified 5089 patients over the age <strong>of</strong> 16 who underwent a total <strong>of</strong>5885 procedures between April 2002 and October 2007. Deaths in this groupwere identified by automated database integration with Office <strong>of</strong> NationalStatistics data. Autopsy reports from this institution and surrounding hospitalswere sought. 226/5089 (4.4%) patients died prior to post-operative dischargewith 141(62%) undergoing autopsy. 307/4863 (6.3%) patients died after postoperativedischarge. In contrast to those patients who died in hospital only 21(7%) had an autopsy (p