P49CTEN positively regulates cell migration in colorectal cancerAMA Albasri 1 ,RSeth 1 , S Crook 1 , D Jackson 1 , TMAM Elsaba 1 ,SLo 3 , L Martinez-Pomares 2 ,MIlyas 1 .1 Divison <strong>of</strong> Pathology, School <strong>of</strong> Molecular Medical Sciences, QMS,Nottingham University Hospital, UK, 2 Institute <strong>of</strong> Infection, Immunity andInflammation, School <strong>of</strong> Molecular Medical Sciences, QMS,NottinghamUniversity Hospital, UK, 3 Howard Hughes Medical Institute, University <strong>of</strong>Chicago, Chicago, IL.INTRODUCTIONC-Terminal Tensin like (CTEN) is a recently cloned gene which has homologywith the tensin family <strong>of</strong> genes. <strong>The</strong>se genes localized at focal adhesionmolecules and appear to be involved in the regulation <strong>of</strong> cell motility. We havepreviously found that CTEN is over expressed in adenoma in Min (MultipleIntestinal Adenoma) mice. We aimed to evaluate the expression and function <strong>of</strong>CTEN in human colorectal carcinoma.METHODSExpression <strong>of</strong> CTEN gene in 26 human colorectal carcinoma cell lines wasdetected by QR-PCR. This was used to identify cell lines with low expression<strong>of</strong> CTEN for further functional studies. One <strong>of</strong> these (HCT116) was selected fortransfection with a GFP tagged CTEN expression vector. Establishment <strong>of</strong> astably transfected cell line was verified by Western blotting for both GFP andCTEN. This cell line was then tested for changes in proliferation, apoptosis andmigration compared with stable tranfected empty GFP vector.RESULTSCTEN mRNA was expressed with varying levels in 26 human colorectal celllines but levels were very low in HCT116. Evaluation <strong>of</strong> proliferation andapoptosis showed no difference between the cell lines transfected with GFP-CTEN and GFP alone. <strong>The</strong> migration results showed that cells expressing GFP-CTEN showed a significantly greater level <strong>of</strong> transwell migration than GFPcontrol (p < 001).DISCUSSIONIn this study, we have demonstrated, for the first time that CTEN is able topromote cell migration in HCT116 colorectal carcinoma cell line when it isexpressed.P51RKIP Expression Levels Predict Survival in a Large Cohort <strong>of</strong>Colo-Rectal Cancer PatientsBDoyle 1 ,LScott 2 , S Harden 3 , S Hagan 1 ,WKolch 1 .1 Beatson Institute for Cancer Research, Glasgow, 2 Centre for Oncologyand Applied Pharmacology, University <strong>of</strong> Glasgow, 3 CRUK Clinical TrialsUnit, Beatson West <strong>of</strong> Cancer Scotland Cancer Centre, GlasgowRaf Kinase Inhibitor Protein (RKIP) plays a role in numerous cell signallingpathways which are important in cancer. Decreased expression has been shownin a number <strong>of</strong> human cancers, including breast, prostate and colo-rectalcarcinoma (CRC). In a previous study <strong>of</strong> 200 cases <strong>of</strong> Dukes B CRC weshowed that decreased RKIP expression correlates with a poor prognosis,independent <strong>of</strong> peritoneal involvement, lympho-vascular invasion and tumoursize. Here we set out to validate this result in a larger cohort <strong>of</strong> CRC patients.In this study we used immunohistochemistry to stain a tissue microarray,consisting <strong>of</strong> 1034 patients with CRC (kindly provided by Dr. Nik Zeps,Western Australia Research Tissue Network). <strong>The</strong> slides were stained for RKIPprotein and scored using a semi-quantitative system combining stainingintensity and area stained. Using this system RKIP expression was divided into3 groups; negative, weakly positive and strongly positive.As no difference was seen between the negative and weakly positive group,these were combined and compared with the strongly positive group. Log-Ranktest showed a significant difference between the 2 groups in both overall(p=0.0007) and disease-specific survival (p=0.0024). Median overall survival inpatients with high levels <strong>of</strong> RKIP expression was 72% longer than in those withlow levels <strong>of</strong> RKIP expression (107.6 v 62.5 months).This large study confirms the results <strong>of</strong> our previous work showing RKIP to bea useful prognostic marker which may aid in risk-stratifying patients with CRC.P50An Unusual Stomach Ulcer: Inflammatory My<strong>of</strong>ibroblasticTumourAP Levene 1 ,GHanna 1 , R Goldin 1 .1 St Mary's Hospital, London, United KingdomA 52 year old lady presented with anaemia, she had numerous endoscopieswhere an ulcer was visualised, repeat biopsies showed fibrous tissue andinflammatory cells only with no definitive diagnosis. As the ulcer persisted agastrectomy was performed and on the greater curve a 6cm ulcerated tumourwith rolled edges was identified. <strong>The</strong> tumour was white, extremely firm andextended through the full thickness <strong>of</strong> the stomach into the mesocolon. <strong>The</strong>surrounding lymph nodes were strikingly enlarged.Microscopically the tumour extended into the mesocolon and was composedmainly <strong>of</strong> acellular connective tissue. Numerous lymphoid aggregates withprominent germinal centres were scattered throughout, as were collections <strong>of</strong>eosinophils and plasma cells. <strong>The</strong> lymph nodes all showed marked follicularhyperplasia without malignancy.<strong>The</strong> diagnosis <strong>of</strong> an inflammatory my<strong>of</strong>ibroblastic tumour was made. Thistumour falls within the spectrum <strong>of</strong> lesions formerly known as inflammatorypseudotumours. It is composed <strong>of</strong> my<strong>of</strong>ibroblastic spindle cells accompanied bya mixed inflammatory infiltrate <strong>of</strong> plasma cells, eosinophils and lymphocytes. Itfrequently recurs (25% <strong>of</strong> abdominopelvic tumours) but rarely metastasises. Itusually occurs in children and young adults (mean age 10 years) but can occurthroughout adulthood, as in this case.P52Anal Melanoma: an Intriguing Case ReportCKaur 1 , C Finlayson 1 .1 St.George`s Hospital, LondonAnorectal melanoma comprises 0.25% to 1.25% <strong>of</strong> all the malignanciesoriginating in this anatomic region and is <strong>of</strong>ten mistaken clinically for benignconditions as either haemorrhoids or rectal polyp. We report a case <strong>of</strong> an analpolyp from an elderly female which showed a pleomorphic spindle cellmorphology. Immunohistochemistry was performed for this malignant tumourwith a panel <strong>of</strong> markers to differentiate a poorly differentiated anorectalcarcinoma from GIST and a spindle cell melanoma. <strong>The</strong> tumour cells werestrongly positive for S100, melan – A and CD117 whilst being negative forpancytokeratins. This is a case <strong>of</strong> anal melanoma expressing CD117/c-kitprotein and it highlights an unexpected finding by immunohistochemistry witha potential <strong>of</strong> being misdiagnosed as a GIST/ GANT. Previously some studieshave reported CD117 positivity in a small number <strong>of</strong> anorectal melanomas <strong>of</strong>which a minority have shown c-kit mutation .Anorectal melanomas are highly aggressive and unresponsive to both radicaland local control with a poor 5 yr survival <strong>of</strong> 10-15%. Given the resistance <strong>of</strong>this tumour to conventional chemotherapy and radiation, the incidence <strong>of</strong> the c-kit alteration may represent a novel approach to a gene-directed treatment usinga c-kit inhibitor (Glivec/ Imatinib) similar to that which has been proposed inGISTs. Thus on the basis <strong>of</strong> detection <strong>of</strong> CD 117 expression byimmunohistochemistry in anorectal melanomas, c-kit mutational analysis iswarranted to determine the eligibility <strong>of</strong> this tumour for imatinib targetedtherapy.44 <strong>Summer</strong> <strong>Meeting</strong> (194 th ) 1–4 July <strong>2008</strong> Scientific Programme
P53Assessment <strong>of</strong> peritumoural inflammatory infiltrate providesindependent prognostic information when compared withcurrent pathological criteria in colorectal cancerCSD Roxburgh 1 , JM Salmond 2 ,PG Horgan 1 , DC McMillan 1 ,KA Oien 3 .1 University Department <strong>of</strong> Surgery, Glasgow Royal Infirmary, Glasgow,UK, 2 Department <strong>of</strong> Pathology, Glasgow Royal Infirmary, UK, 3 Division<strong>of</strong> Cancer Sciences and Molecular Pathology, Glasgow UKProvision <strong>of</strong> adjuvant chemotherapy in colorectal cancer is guided bypathological criteria. <strong>The</strong> prognostic value <strong>of</strong> the Petersen Index (PI) has beenvalidated (Morris, Gut 2007;56:1419-1425). Inflammatory cell response at theinvasive edge also confers prognostic value (Jass, Lancet 1987;1:1303-1306).<strong>The</strong> Finnish inflammatory infiltrate score (FS) has recently been validated(Roxburgh<strong>2008</strong> unpublished), however whether this is independent <strong>of</strong> Dukesstage, PI or Jass classification remains unclear.Aim: To investigate the prognostic value <strong>of</strong> the FS in colorectal cancer,compared with existing validated pathological criteria.Methods: 207 patients from 1997-2004. 2 observers scored 3 H+E slidesper specimen. FS was assessed as low or high grade at the invasive front.Specimens were grouped by Jass’ classification. Dukes stage and PI wereconstructed from pathology reports.Results: Median follow-up for survivors was 72 months, during which 81died, 50 <strong>of</strong> cancer. Most were >65 years (60%), colonic tumours (61%) andDukes A/B disease (59%). Univariate analysis <strong>of</strong> A/B disease: age (p
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