2008 Summer Meeting - Leeds - The Pathological Society of Great ...

S5The MRCPath Autopsy ExaminationSLucas 11 Guy's, King's & St Thomas' School of MedicineThe MRCPath examination changed radically in 2005, with the Autopsy andHistopathology/Cytopathology modules separated and becoming noncontingent.The revised full-day autopsy exam enabled a fuller evaluation ofcandidates, but suffers from lack of standardisation in all the three sections(autopsy dissection & presentation, laboratory diagnosis, viva).Along with problems from 1) increasing difficulties in providing training inautopsy procedures and the associated 2) introduction of Autopsy OptionalTraining (AOT) in the near future, and 3) organising autopsy centres within theexam time frame, a new format has been consulted upon and (in general)agreed. The new exam is for those trainees not opting out of autopsy practice.In outline this will be:A. a workplace based assessment (WPBA) of actual autopsy dissectioncompetence• undertaken after stages A+B of training, at the mutual convenience of traineeand assessors• at the trainee’s home mortuary, or the regional examiner’s if appropriate• assessed by the local educational supervisor plus a visiting regional examiner• to be completed within 3 hours, including write up and documentation ofcause of deathB. Once a trainee has satisfied this WPBA, a centralised part 2 examinationwith all candidates in one place, undertaken twice a year. This includes:• critical evaluation of autopsy reports• viva on communication skills & medico-legal aspects• microscopy and gross diagnosis of autopsy material• biochemical, toxicological and microbiological evaluation• questions on autopsy practice• case interpretation and cause of deathS7The Molecular Pathology of Cervical NeoplasiaCS Herrington 11 University of St AndrewsIt is now accepted that almost all cervical neoplasia is causally associated withhigh-risk human papillomavirus (HPV) infection. However, HPV infection isnot sufficient for the development of neoplasia and other factors are involved.HPV integration has emerged as an important factor in the progression of HPVassociatedneoplasia and the effects of integration, notably loss of HPV E2expression and up-regulation of HPV E6 and E7 expression, can lead to manyof the molecular features associated with the development of high-gradeintraepithelial and invasive squamous and glandular lesions, for exampletelomerase activation and chromosome abnormalities. Sites of frequentchromosome abnormality include 3q, 5p and 20q, all of which have beenassociated with gain and/or elevated expression of specific genes, for examplethe telomerase gene TERC, the microRNA processor Drosha, and DNAmethyltransferase 3B (DNMT3B) respectively. This is consistent with thesequential methylation of several tumour suppressor gene promoters, notablyMGMT, during the progression of HPV-transfected keratinocytes to anchorageindependence. Thus, both genetic and epigenetic changes appear to beimportant in the progression of HPV-associated neoplasia, driven by the effectsof HPV infection and integration.S6Chromosomal Instability in Colorectal Adenoma toCarcinoma Progression & Early Detection of ColorectalCancerGA Meijer 11 VU University Medical Centre, Amsterdam, The NetherlandsColorectal adenomas are commonly found in individuals over 60 years of age,and only a minority of colorectal adenomas progress to adenocarcinomas. Thisis progression is mostly associated with overt chromosomal instability (CIN). Incontrast to the less frequently occurring microsatellite instability, which iscaused by failing DNA mismatch repair, the mechanisms underlying CIN incolorectal adenoma to carcinoma progression are still largely obscure.We have investigated the patterns of CIN in colorectal adenoma tocarcinoma progression by measuring DNA copy number changes witharrayCGH. Amongst others, frequent DNA copy number alterations onchromosomes 13q and 20q turned out to affect mRNA and miRNA expressionof multiple genes like AURKA and the miRNA cluster mir-17-92.Apart from mutations and DNA copy number alterations, also promoterhypermethylation is an important factor in colorectal carcinogenesis. Whencomparing promoter hypermethylation and DNA copy number changes indifferent stages of colorectal carcinogenesis, promoter hypermethylationoccurred earlier. In addition, also specific associations between DNA copynumber alterations and promoter hypermethylation occurred like promotermethylation of GATA-4 and p16INKA4 that were inversely related tochromosomal loss at 15q11-21 and gain at 20q13 respectively (P values: 3.8 x10-2 and 4.5 x 10-2 respectively).Current challenge is to translate this knowledge into approaches formolecular early diagnosis of colorectal cancer, like stool DNA based tests.Methylation markers already have yielded promising results, but we also havegenerated pilot data for detecting DNA copy number alterations in stool derivedDNAS8Occult Lymphoproliferative DisordersAS Jack 11 HMDS, St James's Institute of Oncology, LeedsThe use of sensitive flow cytometric and molecular diagnostic tests has led tothe detection of low level lymphoproliferative disorders in increasing numbersof healthy individuals. In the case of CLL it is estimated that around 3% of theadult population may be affected and a similar proportion can be shown to havea paraprotein. There is less Information on the prevalence of other forms ofoccult lymphoproliferative disorder, but it is clear that low levels of B-celllymphoproliferative disorders with non-CLL phenotypes are also relativelycommon. This is consistent with the frequent detection of t(14;18) by sensitivePCR in healthy individuals. Clonal T-cell lymphoproliferative disorders,usually with a cytotoxic T-cell large granular lymphocyte (LGL) phenotype, arealso frequently encountered in the investigation of lymphocytosis detected onroutine blood counts.The detection of these conditions in the course of other forms of medicalinvestigation and treatment raises a number of important issues. If the patienthas Diffuse Large B-cell Lymphoma the possibility that disease has arisen bytransformation of an underlying indolent lymphoma will need to be addressedand this may have prognostic implications. In other patients the detection of anoccult lymphoproliferative disorder may cause significant anxiety and requirefollow up commensurate with the risks of disease progression. Finally, theclinical consequences and disease associations of clonal T-LGL disorders arewell recognised. In contrast, the possible health effects of the more numerousB-cell disorders remains poorly understood.Summer Meeting (194 th ) 1–4 July 2008 Scientific Programme89