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

P61Proportion of Tumour Cells and Stroma – An Inexpensive butReliable Predictor of Patient Survival in Colorectal CancerM Dattani 1 , P McShane 2 , D Treanor 1 , G Hutchins 1 , J Grabsch 1 ,JM Brown 2 , H Thorpe 2 , DG Jayne 3 , PJ Guillou 3 ,WMueller 4 ,PQuirke 1 , H Grabsch 11 Pathology and Tumour Biology, Leeds Institute of Molecular Medicine,University of Leeds, UK, 2 Clinical Trials Research Unit, University ofLeeds, UK, 3 Academic Unit of Surgery, St James's University Hospital,Leeds Teaching Hospitals NHS Trust, UK, 4 GemeinschaftspraxisPathologie, Starnberg, GermanyRecent studies indicate that tumour growth is determined by cancer cellsthemselves as well as by tumour stroma. Although expression studies haveshown that stroma-like gene expression patterns are related to cancerprogression, tumour components have not been quantified in a large series ofcolorectal cancer (CRC).Performing point counting on virtual HE stained slides, we analysed therelative proportion of tumour and stroma in two independent CRC series: CRC-G (n=147, consecutive cases from one German hospital) and CLASICC(n=150, cases from a UK randomised clinical trial). Results were comparedwith clinicopathological parameters and patient survival. Cut offs for Kaplan-Meier analyses were established using ROC curve analyses.High tumour cellularity was associated with prolonged survival in CRC-G(p=0.011) and in CLASICC (p=0.033) and high proportion of stroma wasrelated to poor patient survival in CRC-G (p=0.002) and in CLASICC(p=0.015). No significant associations were found with any otherclinicopathological parameters.This is the first study that objectively quantified the morphological tumourcomponents in a large series of CRC. It demonstrates that this inexpensivemorphometric method can reproducibly predict patient prognosis in CRCconfirming data from a previous much smaller study in CRC. Although, wecurrently do not fully understand the molecular mechanisms that regulate theproportion of stroma in a tumour, the morphological quantification of tumourcomponents may be a useful marker for patient stratification to therapiestargeting tumour stroma .P63Routine Staining of Gastrointestinal Biopsies in the UnitedKingdomMKoenig 1 , JB Schofield 21 Brighton & Sussex University Hospitals NHS Trust, 2 Maidstone &Tunbridge Wells NHS TrustA survey was conducted into the routine staining of gastrointestinal biopsies inhistopathology departments within the NHS. We aimed to compare the sole useof HE staining with the use of HE combined with special stains according to thebiopsy site. This project has been endorsed by the Pathology Section of theBritish Society of Gastroenterologists.167 histopathology departments in the United Kingdom were contacted usingan email questionnaire. The following question was asked: Which stains areroutinely used in your department when staining biopsies from the oesophagus,stomach, duodenum, small bowel and large bowel?Valid return rate was 92 of 167 departments (55%). Approximately two thirdsof departments only employ HE for assessment of oesophageal biopsies. Thedistribution with regard to staining of gastric biopsies was approximately equalwith 50% HE-only to 50% HE combined with special stains (mostly AB-PASand Giemsa). Duodenal, small and large bowel biopsies are mostly stained withHE-only. No significant difference could be identified between the use ofspecial stains in district general hospitals as opposed to university, teaching orexpert centres.The results of the survey show routine use of special stains to be variable,especially for oesophageal and gastric biopsies. A review of the literature hasshown special stains to enhance sensitivity and specificity for the detection ofpathological abnormalities, especially metaplasia and infections. The diversityof routine staining practice within the NHS highlights the need to discussguidelines. A consensus on best practice is desirable.P62A Novel SNP in the 5'UTR of ATP5A1 is Associated withReduced Gene Expression in Colorectal Cancer Cell LinesJ Keeley 1 ,RSeth 1 ,SCrook 1 , D Jackson 1 , MIlyas 11 Department of Pathology, QMC, NUH. NottinghamIntroductionAllelic imbalance (AI) at 18q is a common event in colorectal cancer (CRC).Recently, a loss of function mutation in the gene Atp5a1 has been found to beassociated with increased risk of tumour progression in Min (Multiple IntestinalNeoplasia) mice. The human ortholog maps to chromosome 18q and thus weinvestigated whether ATP5A1 could be a target of 18q allelic loss.MethodsEighteen CRC cell lines were studied for ATP5A1 mutation using PCR andHigh resolution Melting analysis. Samples showing aberrant melting curves onthe HRM were sequenced. The expression of ATP5A1 mRNA was investigatedusing real-time quantitative PCR.ResultsHRM analysis identified several previously described SNPs but loss offunction somatic mutations were not found within ATP5A1. A novel A to Gtransition was discovered in exon 1. This change is located in the 5’UTR ofATP5A1 and is present in LOVO/HCT116 (heterozygous) andRKO/SW480/SW620 (homozygous). All cell lines expressed ATP5A1 mRNAand further analysis demonstrated that cell lines carrying this change expressedlower levels of ATP5A1 mRNA than those with the wild type sequence(p = 0.05).ConclusionSomatic mutations of ATP5A1 were not found in this study. The identicalnature of the sequence change in the 5’UTR in 5 different cell lines suggest thatthis is more likely a novel SNP than a somatic change. The lower level of geneexpression associated with this change is of uncertain significance but may givean increased risk of tumour progression.P64Perforated Amoebic Colitis Complicating Cortico-steroid andChemotherapy for Metastatic Adenocarcinoma of UnknownOriginN Momtahan 1 ,DScott 2 , JP Narain 21 Bradford Royal Infirmary, 2 Harrogate District HospitalFulminant amoebic colitis is a rare form of amoebiasis in which thetrophozoites of Entamoeba histolytica invade the colonic wall resulting inmassive necrosis of wide segments of large bowel. It begins as a mucosal ulcer,which expands within the submucosa.Fulminant amoebic colitis is associated with a high mortality despiteaggressive treatment with anti- microbial agents. It has been reported in patientswith asymptomatic amoebiasis who are given corticosteroid for anotherindication and should be considered in the differential diagnosis of patients whodevelop fever and diarrhoea after starting such therapy. In fact, corticosteroiduse is the one factor that predicted the likelihood of multi-organ failure inpatients with fulminant amoebic colitis. Despite a high incidence of colonicperforation (some series reporting incidences as high as 87%, the majority ofthese having multiple perforations), the finding of a soft compressible abdomenis present in as many as 65% of cases of fulminant amoebic colitis. Earlylaparatomy may decrease mortality from nearly 100% to 40%. Demonstrationof erythrophagocytic amoebae in the stool by microscopic examination is 100%specific for invasive amoebiasisWe hereby present a case that developed fulminant amoebic colitis andcolonic perforation after receiving corticosteroid and chemotherapy formetastatic adenocarcinoma of unknown origin.Summer Meeting (194 th ) 1–4 July 2008 Scientific Programme47