P25An Interesting Case <strong>of</strong> Indigestion{P} R Arora, P PichmanWest Herts Hospital NHS Trust, Northwood, <strong>London</strong>, United KingdomPancreatic heterotopia or aberrant pancreatic tissue in not an uncommoncondition in the antrun and pyloric canal. Most <strong>of</strong> these are howeverunsymptomatic. Some which become symptomatic require surgicalresection.<strong>The</strong>y can mimic other upper gastrointestinal pathologiesendoscopically and histopathologically.We present an interesting case <strong>of</strong> distal gastrectomy performed forsymptoms <strong>of</strong> indigestion and pyloric obstruction in a 70 year old male.Macroscopically there was a 12mm firm area at the antrum which on histologyshowed islands <strong>of</strong> varying sizes <strong>of</strong> glandular structures within the muscularispropira which were interspersed with smooth muscle and fibrous tissue.Occasional foci <strong>of</strong> heterotopic pancreatic tissue including acinar cells andneuroendoocrine islet-like cells were seen. <strong>The</strong>se apprearences are <strong>of</strong>adenomyoma or myoepithelial hamartoma which is thought to be a congenitalabnormality due to separation <strong>of</strong> fragments <strong>of</strong> pancreatic tissue from the mainmass <strong>of</strong> the pancreas during rotation <strong>of</strong> the forgut.P26Evaluation <strong>of</strong> Genomic Instability in Sporadic ColorectalCancers: Array-Comparative Genomic HybridisationOutperforms Flow Cytometric Analysis{P} G Poulogiannis 1 ,KIchimura 1 , NG Miller 1 , IM Frayling 2 ,RG Morris 3 , DJ Harrison 3 , VP Collins 1 , A Ibrahim 1 , AH Wyllie 1 ,MJ Arends 11 University <strong>of</strong> Cambridge, Pathology Department, Cambridge, UnitedKingdom, 2 University Hospital <strong>of</strong> Wales, Institute <strong>of</strong> Medical Genetics,Cardiff, United Kingdom, 3 University <strong>of</strong> Edinburgh, PathologyDepartment, Edinburgh, United KingdomColorectal cancers (CRCs) show at least two patterns <strong>of</strong> genomic instability:chromosomal instability resulting in aneuploidy, and microsatellite instability(usually occurring in near-diploid CRCs), with inactivation <strong>of</strong> the DNAmismatch repair (MMR) pathway, and sometimes both patterns or neither. Inthis study, we evaluated chromosomal instability in >100 sporadic CRCs using1Mb array-comparative genomic hybridisation (aCGH) to assess DNA copynumber alterations <strong>of</strong> the whole genome with arrays <strong>of</strong> 2904 cloned DNAinserts (mean clone size 152kb) spaced on average 0.97 Mb apart. <strong>The</strong>quantitative assessment <strong>of</strong> DNA copy number changes by aCGH identifiedmany genomic abnormalities ranging from copy number variations <strong>of</strong> entirechromosomes and chromosomal arms to small micro-deletions and micro-gains<strong>of</strong> chromosomal subregions. <strong>The</strong> overall DNA content <strong>of</strong> these CRCs was alsoevaluated by the quantitative assessment <strong>of</strong> propidium iodide labelled tumournuclei by flow cytometry (FCM). Comparison <strong>of</strong> FCM DNA histograms withaCGH analyses showed that a significant proportion <strong>of</strong> tumours with a neardiploidDNA content by FCM exhibited >1000 DNA copy number changes byaCGH indicating widespread chromosomal instability. This discrepancy islargely due to tumours displaying approximately equivalent numbers <strong>of</strong> DNAgains and losses resulting in an overall near-diploid DNA content. Most (>85%)MMR defective CRCs showed near-diploidy with few DNA breakpoints byaCGH. Furthermore, we developed a computational method to correlate aCGHdetectedDNA copy number changes in CRCs with published changes in theexpression levels <strong>of</strong> genes localised to the relevant chromosomal regions inorder to identify novel putative oncogenes, such as LIVIN that showed copynumber gains in ~70% <strong>of</strong> CRCs. We conclude that flow cytometric analysis <strong>of</strong>DNA ploidy underestimates chromosomal instability in CRCs, whereas aCGHprovides a more accurate evaluation <strong>of</strong> chromosomal instability and canidentify novel putative cancer-related genes.P27Poster withdrawnP28<strong>The</strong> Predictive Value for Adenocarcinoma <strong>of</strong> HGPIN andAtypical Small Acinar Proliferation (ASAP) in ProstateNeedle BiopsiesL Hatsell, {P} N MayerUniversity Hospitals <strong>of</strong> Leicester NHS Trust, Leicester, United KingdomBackground and Aims: High grade prostatic intraepithelial neoplasia(HGPIN) is characterised by architecturally benign prostatic glands lined bycytologically atypical cells. Atypical small acinar proliferation (ASAP), ratherthan being a specific diagnostic entity, is a term used to describe a focus <strong>of</strong>glands which are suspicious for adenocarcinoma but for a variety <strong>of</strong> reasons fallbelow the threshold for a definite cancer diagnosis. In this retrospective audit<strong>of</strong> prostate needle biopsies, we compared our own diagnostic rates <strong>of</strong> HGPINand ASAP and their predictive values for a subsequent diagnosis <strong>of</strong>adenocarcinoma against published standards. Methods: We identified 162biopsies with an initial diagnosis <strong>of</strong> HGPIN and/or ASAP and determined howmany <strong>of</strong> these had adenocarcinoma on re-biopsy. We compared this with acontrol group with a benign first biopsy. Results: In 2004 and 2005, HGPINaccounted for 6.9% and 5.8% <strong>of</strong> all prostate biopsies, respectively. Our‘suspicious rate’ (ASAP and ASAP/HGPIN) was 2.6% in 2004 and 2.3% in2005. <strong>The</strong> predictive value for adenocarcinoma in the HGPIN group was 15%which was similar to the control group <strong>of</strong> 13% (P=0.746). <strong>The</strong> predictive valuefor ASAP was 24% (P=0.286) and combined ASAP/HGPIN 33% (P=0.150).Conclusion: Our diagnostic rates for HGPIN and ASAP are withinrecommended guidelines. <strong>The</strong> predictive value for adenocarcinoma in theisolated HGPIN group is virtually the same as in the control group who had abenign first biopsy. <strong>The</strong> predictive value <strong>of</strong> ASAP and ASAP/HGPIN is higher(although failing to reach statistical significance).<strong>The</strong>se results are in keepingwith recent published series and suggest a diagnosis <strong>of</strong> isolated HGPIN doesnot justify immediate re-biopsy whereas ASAP or combined ASAP/HGPINprobably does.34 <strong>Winter</strong> <strong>Meeting</strong> (191 st ) 3–5 January <strong>2007</strong> Scientific Programme
P29Utility <strong>of</strong> Polyclonal anti-PSA and 34betaE12 ImmunostainingFor Differentiating Prostatic Carcinoma from UrothelialCarcinoma{P} M Varma, B Jasani, PN Mathews, SN Datta, MB Amin1 University Hospital <strong>of</strong> Wales, Cardiff, United Kingdom, 2 EmoryUniversity, Atlanta, United StatesPSA and 34βE12 immunohistochemistry has been shown to be useful fordifferentiating high-grade prostatic adenocarcinoma (Pca) from Urothelialcarcinoma (Uca). Polyclonal antibody to PSA (pPSA) has been reported to bemore sensitive than monoclonal anti-PSA in high-grade PCa.However, published studies examined only morphologically unequivocalcases. We retrospectively evaluated the utility <strong>of</strong> pPSA and 34βE12immunostaining in 16 cases that had been signed out as “poorly differentiatedcarcinoma: ?PCa,?Uca” after immunostaining with monoclonal antibodies toPSA, PSAP and/or CEA.Using pPSA and 34βE12, a definite diagnosis could be established in 15(93.8%) <strong>of</strong> the 16 originally equivocal cases [9 Pca (pPSA+, 34βE12 -), 6 Uca(pPSA-, 34βE12 +)]. In 2 <strong>of</strong> these cases the possibility <strong>of</strong> synchronous PCa andUCa had originally been considered in view <strong>of</strong> patchy immunoreactivity withmonoclonal anti-PSA, but pPSA showed diffuse positivity establishing adiagnosis <strong>of</strong> PCa. <strong>The</strong> remaining case was negative for pPSA and 34βE12, andan extended immunohistochemical panel was also non-diagnostic. Clinicalfindings in this case favored UCa but no follow-up was available.Our findings confirm the clinical utility <strong>of</strong> a simple immunohistochemicalpanel composed <strong>of</strong> pPSA and 34βE12 for differentiating high-grade Pca fromUca.P30Microwave Pre-treatment Improves the Sensitivity <strong>of</strong>34betaE12 as a Marker for High-grade Urothelial Carcinoma{P} M Varma, S Wozniak, B JasaniUniversity Hospital <strong>of</strong> Wales, Cardiff, United KingdomHistopathologic distinction between high-grade urothelial carcinoma (HG-UCa)and prostate adenocarcinoma is critical for appropriate therapy.High molecular weight cytokeratin monoclonal antibody, 34βE12 has beenshown to be a sensitive marker for HG-UCa. A recent study found thesensitivity <strong>of</strong> 34βE12 immunostaining in HG-UC to be significantly greaterwith the use <strong>of</strong> microwave heat retrieval, as compared to enzyme predigestion.We describe two cases (1 TURP, 1 prostate needle biopsy) in which the lowersensitivity <strong>of</strong> 34βE12 immunoreactivity after enzyme predigestion resulted indiagnostic difficulty. In both cases, the poorly differentiated carcinoma wasnegative for PSA and with 34βE12 used after enzyme predigestion at outsideinstitutions and the overall appearances were considered most in keeping withprostate cancer.On repeat immunostaining in our department, in both cases the tumour cellswere negative for PSA and PSAP but diffusely and intensely positive on34βE12 immunostaining performed after microwave pretreatment. Based on themorphology and immunopr<strong>of</strong>ile, a diagnosis <strong>of</strong> HG-UCa was made on bothcases. This diagnosis was confirmed following cystoprostatectomy in one case,no relevant follow-up is available to date on the other case.We conclude that heat retrieval is the pre-treatment <strong>of</strong> choice when 34βE12immunostaining is performed to confirm a diagnosis <strong>of</strong> urothelial carcinoma.P31An Evaluation <strong>of</strong> the Clinical Utility <strong>of</strong> Pelvic Lymph NodeFrozen Section Examination Prior to Radical Prostatectomy{P} LJ Aitken, H Kynaston, DFR Griffiths, M VarmaUniversity Hospital <strong>of</strong> Wales, Cardiff, United KingdomIn the current era <strong>of</strong> PSA screening, prostate cancer deposits within pelviclymph nodes <strong>of</strong> patients considered for radical prostatectomy are generallysmall and the utility <strong>of</strong> frozen section (F/S) examination <strong>of</strong> these lymph nodesprior to radical prostatectomy is uncertain.In our institution, 101 pelvic lymph node F/S examinations prior to plannedradical prostatectomy were performed between 1996 and 2005. <strong>The</strong> lymphnodes were partially submitted for F/S examination and entirely submitted afterfixation for definitive histology.Metastatic tumour was found in only 2 (2%) <strong>of</strong> the cases while there were 3false negative cases. <strong>The</strong> remaining 96 cases were negative on F/S anddefinitive histology.Review <strong>of</strong> the 3 false negative cases confirmed the absence <strong>of</strong> metastatictumour in the cryostat sections. Tumour deposits were found only in paraffinsections from deeper levels <strong>of</strong> cryostat blocks in two cases and only inadditional blocks submitted after fixation in the third case. Thus, two <strong>of</strong> thethree false negative cases would have been missed even if the nodes had beensubmitted in total for F/S examination.We conclude that pelvic lymph node frozen section examination prior toradical prostatectomy is not cost effective.P32Bone Marrow-Derived Renal Parenchymal Cells RespondPoorly to the Renotropic Actions <strong>of</strong> Epidermal Growth FactorT-H Yen 3 , MR Alison 2 , RA Goodlad 1 , WR Otto 1 ,HT Cook 5 ,NA Wright 1 , {P} R Poulsom 11 Cancer Research UK - <strong>London</strong> Research Institute, <strong>London</strong>, UnitedKingdom, 2 Queen Mary’s School <strong>of</strong> Medicine and Dentistry, <strong>London</strong>,United Kingdom, 3 Chang Gung Memorial Hospital, Taipei, Taiwan,4 Chang Gung University, Taoyuan, Taiwan, 5 Imperial College, <strong>London</strong>,United KingdomA small percentage <strong>of</strong> regenerating epithelial cells are derived from bonemarrow (BM) cells following different types <strong>of</strong> renal injury. We reportedpreviously that these enter S-phase <strong>of</strong> the cell cycle to assist regeneration, butwe are concerned that they may not respond normally to growth controls, andbe undesirable rather than useful for organ regeneration.We tested whether BM-derived epithelial cells respond to epidermal growthfactor (EGF) in lethally irradiated female mice transplanted with male wholeBM cells. Six-weeks later they received pegylated colony stimulating factor (p-GCSF), EGF, and HgCl 2 singly or in combination, and were killed after 4 days,with tritiated thymidine given one hour earlier to label cells in S-phase.Tubular injury scores and serum urea nitrogen levels were high after HgCl 2injection and reached uremia, but EGF protected from such extreme damage.To explore the cell origin underlying this rescue, kidney sections weresubjected to a “four-in-one” analytical technique for identification <strong>of</strong> cell origin,tubular phenotype, tubular basement membrane and S-phase status.Transplanted BM contributed ~ 1% <strong>of</strong> proximal tubular epithelium inundamaged kidneys, ~ 3% in HgCl 2-damaged kidneys, but without furtherincrease after either EGF or p-GCSF injection. Only ~ 0.5% proximal tubularcells were in S-phase without damage, increasing to ~ 7-8% after HgCl 2,and to~ 15% for EGF+HgCl 2 mice. BM contributed ~ 1 in 15 <strong>of</strong> the S-phaseproximal tubular cells after HgCl 2, but only ~ 1 in 30 after EGF+ HgCl 2treatment.Thus, BM-derived tubular cells are compromised in their ability to respond toa normal renal growth factor, and thus have a selective disadvantage that mightcause them to be lost.<strong>Winter</strong> <strong>Meeting</strong> (191 st ) 3–5 January <strong>2007</strong> Scientific Programme35