2007 Winter Meeting - London - The Pathological Society of Great ...

S13Immunohistochemical Markers of Lymphoma{P} DY MasonUniversity of Oxford, Oxford, United KingdomBy the early 1990s the advent of “paraffin-reactive” anti-white cell monoclonalantibodies had transformed routine haematopathology and opened the way tothe REAL classification (and to its direct successor, the WHO-sponsoredscheme). As a result most lymphomas can be diagnosed today without greatdifficulty by morphology and immunohistology. However, a few entitiesremain “diagnoses of exclusion” (e.g. lymphoplasmacytoid lymphoma andmarginal zone lymphomas), partly defined by the absence of specificimmunohistological features. New markers are likely to prove valuable in suchsettings, and they may also allow subdivision of existing lymphoma categories.For example, the immunohistological recognition of subtypes of diffuselymphoma and of T cell lymphomas is an obvious area for future progress.There is also much interest in predicting prognosis in lymphomas on the basisof immunohistology, but the scope of this approach can be overestimated: themost robust markers are likely to be among the minority that directly reflect anunderlying genetic lesion. Finally, the number of immunohistological markersdetectable in paraffin sections continues to grow steadily, both throughcommercial production and from initiatives such as the Human Protein Atlas. Inconsequence there is still substantial scope for new immunohistological insightsinto lymphoma.S14Molecular biology and molecular markers of lymphoma{P} M-Q DuUniversity of Cambridge, Department of Pathology, Cambridge, UnitedKingdomMolecular genetic features are one of the essential elements used in WHOclassification of tumours of lymphoid tissues. Detection and characterisation ofgenetic abnormalities or molecular signatures valuable in lymphoma diagnosis,classification and prognosis have been continuously gaining attention inresearch since the introduction of WHO classification. Such research isparticularly accomplished by the completion of the human genome project andthe advent of high-throughput research tools such as genomic and expressionmicroarray analysis. There are a number of important advances in ourunderstanding of molecular genetics and pathobiology of several lymphomasubtypes. Notable examples include 1) the finding of the oncogenic products oft(11;18)/API2-MALT1, t(1;14)/IGH-BCL10 and t(14;18)/IGH-MALT1 inMALT lymphoma commonly targeting the pathway leading to NFκBactivation, and demonstration of gastric MALT lymphoma with t(11;18)resistant to H pylori eradication; 2) identification of ZAP70 expression as asurrogate marker for CLLs that carry unmutated rearranged immunoglobulingene and show poor clinical outcome; 3) sub-classification of diffuse large Bcell lymphoma into germinal centre B cell-like (GCB) and activated B cell-like(ABC) subtypes with distinct molecular and clinical features by geneexpression profiling, with the ABC subtype characterised by the enhancedNFκB activities and poor prognosis. These findings have direct implications inclinical management of patients with these diseases.S15Our changing view of the genome: implications for pathology{P} PA HallCentre for Cancer Research & Cell Biology, Division of Pathology,Queen's University, Belfast, United KingdomThe concept of the gene has evolved over the past century and the model of‘one gene one protein’ proposed by Beadle & Tatum has been radically alteredin the molecular era. Furthermore the various genome sequencing projectsdemonstrated that the number of ‘genes’ is far less than had been anticipated:perhaps less than 30000 in man, whereas Sacchoromyces cerevisiae has ~6300and Drosophila melanogaster ~12500. The massive increase in cellularcomplexity (tissues, organs, physiology etc) in metazoa, and in particular invertebrates, thus seems out of proportion to the numeric increase in genenumber and the informational content inherent in the encoded open readingframes. How can this paradox be resolved? Alternate splicing of RNA to givediverse mRNA species encoding numerous protein isoforms has a significantcontribution to the resolution of this paradox. In man it may be that as much as90% of the expressed genes are spliced so that the ~30000 genes may encodeconsiderably more protein species. In addition, a range of potential posttranslational modifications also contributes to the increased complexity anddiversity of protein species. In addition, the non-coding RNA has considerableinformational content both in terms of cis and trans acting elements. By suchroutes the proteome is massively increased giving a much larger array ofpotential structural and regulatory protein species, thus creating the necessarybuilding blocks for metazoan organisms. Central to the optimal functioning ofthese mechanisms is the correct levels of the correct elements of regulatory andother protein arrays. Controlling the stoichiometry of critical polypeptides thenbeing central to normal cell function. Disease can then be a consequence ofalterations not only in the coding sequence of open reading frames, but also innon coding regions. Moreover, no longer should we think of disease in terms ofa gene-specific mutation but more widely accept that disease can be isoformspecific. Furthermore genetic variation within the population provides asubstrate for small differences in coding and non coding regions and hence inthe subtle expression patterns of diverse proteins and hence subtly alteringstoichiometry. Using examples from my previous studies in p53 and septinbiology these ideas will be explored and their implications for pathologydeveloped. It is essential that the discipline grasp the intellectual and technicalchallenges inherent in our changing view of the genome if pathology is totranslate such developments into clinical practice.S16LBC in Non-Gynaecological Cytology{P} JE McCarthySt Marys NHS Trust, Paddington,London, United KingdomLiquid based preparation of non-gynaecological samples has many benefits andsome limitations. The method discussed here is ThinPrep processing using theT2000. In our institution, we routinely process all bronchial samples includingsputa by this method exclusively. ThinPrep processing has improved our pickup of primary lung carcinomas compared to direct spread technique and isquicker and easier to screen.Thyroid FNAs are prepared using a combination of direct spread MGG stainedslides together with a ThinPrep slide. This combination provides traditionalsmears coupled with a Pap stained method with the added benefit blood lysis.We avoid using ThinPrep for other samples such as fluids and especially lymphnodes, notably for reasons of cost and as lymph node morphology is poorlypresented in ThinPrep preparations.This methodology is ideal for use in clinical situations such as thebronchoscopy suite where spreading of material may be suboptimal and toretain well preserved material for special stains and for immunocytochemistry.Its use should be tailored to the individual clinical situation and moreimportantly to the specimen type for maximum benefit and cost effectiveness.Winter Meeting (191 st ) 3–5 January 2007 Scientific Programme61