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

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 of Pathology, School of Molecular Medical Sciences, QMS,Nottingham University Hospital, UK, 2 Institute of Infection, Immunity andInflammation, School of Molecular Medical Sciences, QMS,NottinghamUniversity Hospital, UK, 3 Howard Hughes Medical Institute, University ofChicago, Chicago, IL.INTRODUCTIONC-Terminal Tensin like (CTEN) is a recently cloned gene which has homologywith the tensin family of genes. These genes localized at focal adhesionmolecules and appear to be involved in the regulation of 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 ofCTEN in human colorectal carcinoma.METHODSExpression of CTEN gene in 26 human colorectal carcinoma cell lines wasdetected by QR-PCR. This was used to identify cell lines with low expressionof CTEN for further functional studies. One of these (HCT116) was selected fortransfection with a GFP tagged CTEN expression vector. Establishment of 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 of proliferation andapoptosis showed no difference between the cell lines transfected with GFP-CTEN and GFP alone. The migration results showed that cells expressing GFP-CTEN showed a significantly greater level of 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 ofColo-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 of Glasgow, 3 CRUK Clinical TrialsUnit, Beatson West of 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 of human cancers, including breast, prostate and colo-rectalcarcinoma (CRC). In a previous study of 200 cases of Dukes B CRC weshowed that decreased RKIP expression correlates with a poor prognosis,independent of peritoneal involvement, lympho-vascular invasion and tumoursize. Here we set out to validate this result in a larger cohort of CRC patients.In this study we used immunohistochemistry to stain a tissue microarray,consisting of 1034 patients with CRC (kindly provided by Dr. Nik Zeps,Western Australia Research Tissue Network). The 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 of RKIP expression was 72% longer than in those withlow levels of RKIP expression (107.6 v 62.5 months).This large study confirms the results of our previous work showing RKIP to bea useful prognostic marker which may aid in risk-stratifying patients with CRC.P50An Unusual Stomach Ulcer: Inflammatory MyofibroblasticTumourAP 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. The tumour was white, extremely firm andextended through the full thickness of the stomach into the mesocolon. Thesurrounding lymph nodes were strikingly enlarged.Microscopically the tumour extended into the mesocolon and was composedmainly of acellular connective tissue. Numerous lymphoid aggregates withprominent germinal centres were scattered throughout, as were collections ofeosinophils and plasma cells. The lymph nodes all showed marked follicularhyperplasia without malignancy.The diagnosis of an inflammatory myofibroblastic tumour was made. Thistumour falls within the spectrum of lesions formerly known as inflammatorypseudotumours. It is composed of myofibroblastic spindle cells accompanied bya mixed inflammatory infiltrate of plasma cells, eosinophils and lymphocytes. Itfrequently recurs (25% of 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% of all the malignanciesoriginating in this anatomic region and is often mistaken clinically for benignconditions as either haemorrhoids or rectal polyp. We report a case of an analpolyp from an elderly female which showed a pleomorphic spindle cellmorphology. Immunohistochemistry was performed for this malignant tumourwith a panel of markers to differentiate a poorly differentiated anorectalcarcinoma from GIST and a spindle cell melanoma. The tumour cells werestrongly positive for S100, melan – A and CD117 whilst being negative forpancytokeratins. This is a case of anal melanoma expressing CD117/c-kitprotein and it highlights an unexpected finding by immunohistochemistry witha potential of being misdiagnosed as a GIST/ GANT. Previously some studieshave reported CD117 positivity in a small number of anorectal melanomas ofwhich 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 of 10-15%. Given the resistance ofthis tumour to conventional chemotherapy and radiation, the incidence of 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 of detection of CD 117 expression byimmunohistochemistry in anorectal melanomas, c-kit mutational analysis iswarranted to determine the eligibility of this tumour for imatinib targetedtherapy.44 Summer Meeting (194 th ) 1–4 July 2008 Scientific Programme