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

P41MCPH1, a potential predictor for response to cancerchemotherapySM Bell 1 , A Shaaban 2 , C Walker 1 , A Hanby 1,2 ,VSpeirs 1 ,EE Morrison 1 .1 Leeds Institute of Molecular Medicine, Wellcome Trust, St James'sUniversity Hospital, Leeds, 2 Department of Histopathology, LeedsTeaching Hospitals NHS Trust, LeedsWe have shown MCPH1, a DNA damage response protein involved in theregulation of BRCA1, is defective in one form of microcephaly. The MCPH1locus (8p23) is frequently deleted in many tumour types including breast cancerand this depletion is associated with a poor prognosis.Reduced expression of MCPH1 causes premature chromosome condensation(PCC). Using time-lapse imaging we have identified further mitotic defectsincluding slower mitotic progression, aberrant chromosomal congression andmicronuclei formation in MCPH1 deficient cells. This mitotic phenotypesuggests that loss of MCPH1 function could cause mitotic errors with resultantaneuploidy.Chemotherapeutic agents such as Taxol require a functional spindlecheckpoint for the induction of apoptosis in cancer cells. Our data indicates thatMCPH1 plays a role in the spindle checkpoint. We hypothesise that, while germline defects in MCPH1 cause microcephaly, somatic defects may causeaneuploidy development and resistance to some chemotherapeutic agents inbreast cancers.We have demonstrated reduced MCPH1 expression in 17 out of 54 (32%)breast cancers, particularly in higher grade tumours. Interestingly we alsoidentified high levels of MCPH1 expression in 8 out of 36 (22%) low gradebreast cancers, which was associated with a good prognosis. We are nowstudying a larger series of breast cancer samples using tissue micro arrays toinvestigate MCPH1 in a larger cohort in order to validate our initial results andrelate them to patient outcome.P43New Highlights on the Clinical, Biological and PrognosticImplications of p53 Transcriptional Status in Breast CancersTMA Abdel-Fatah 1 , DG Powe 1 , A Jhonson 1 ,M Adamowicz-Brice 2 , AR Green 1 , IO Ellis 1 .1 Division of Pathology, School of Molecular Medical Sciences, Universityof Nottingham, Nottingham, UK, 2 The Children's Brain Tumour ResearchCentre, University of Nottingham, Nottingham, UKAimTo investigate p53 transcriptional activity in determining pathoclinical,prognostic and treatment response in breast carcinoma (BC)MethodsImmunohistochemistry and quantitative scoring was employed to determinep53 transcriptional activity using three of its downstream targets (MDM2, p21and Bcl-2) on 615 successive surgical BC cases with clinical follow up (> 20years). Statistical analysis was performed on the whole patient series , in nodenegativeand node-positive subgroups, and those that had/had not receivedadjuvant treatment.ResultsSix p53 phenotypes were identified that exhibited 2 main clinical outcomes:(a) Good prognosis group including an MDM2–overexpression phenotype(p53-/MDM2++), and active wild-type p53 phenotype (p53-/MDM2+/Bcl2+).These showed favorable clinical parameters (ER-alpha+), occurred in lownuclear grade breast neoplasia (LNGBN), and had significantly reduced tumourrecurrence/distant metastasis after hormonal-therapy (p=0.035).(b) Poor prognosis group including the mutational phenotypes: point mutation(p53++/MDM2+), null mutation (p53-/MDM2-/p21-), and inactive wildphenotype (p53-/MDM2+/Bcl2-). These tumours were characterised byaggressive features and did not benefit from adjuvant therapy. Thep53++/MDM2+/p21+ phenotype had the worst prognosis especially in ER-positive patients given adjuvant chemotherapy (p=0.02). Compared to the pointmutation phenotype, p53 null mutation phenotype showed increased ER andPgR-expression, and occurred more frequently in LNGBN with low tumourstage.Conclusionp53 status determined by transcriptional activity has prognostic and treatmentpredictive significance in breast carcinoma and could assist routine clinicaldecision-making regarding optimum treatment selection.P42Case Report – Tubular Adenoma Colonised by LCISSS Roberts 1 , AG Douglas-Jones 1 .1 University Hospital of Wales, Cardiff, UKWe present the case of a 52 year old woman with a screen detected 10mm welldefinedrounded mass in her right breast. Ultrasound examination wascompatible with a fibroadenoma (U2). Core biopsy showed crowded acinarstructures surrounded by P63 positive myoepithelial cells but expanded bylobular carcinoma in-situ (LCIS).Excision biopsy was performed to establish the nature of the mass lesion.Excision biopsy showed an ovoid 10 x 7mm breast tumour composed of closelypacked acini with minimal intervening stroma with the architecture of tubularadenoma. 99% of the acini were distended by monotonous cells with roundednuclei and clear cytoplasm containing acidic and neutral mucins. Themorphological appearance of LCIS was confirmed by lack of E-Cadherinmembrane positivity. The acini were surrounded by SMA positive epithelialcells and no stromal invasion could be identified (confirmed with cytokeratinimmunohistochemistry).Fibroadenomas in which there is focal LCIS replacing the epithelial elementare described. This case is a well-defined mass composed of closely packedtubules with minimal intervening stroma with the architecture of a tubularadenoma. The epithelial component appears to have been replaced by LCISwithout invasion. Tubular adenoma is a rare lesion (comprising 0.01%) ofbenign well-defined fibroepithelial lesions and diffuse replacement of theepithelial element by LCIS has not been previously described.P44An Audit of Pathology Reporting of Breast Biopsies in KentWRickaby 1 , G Russell 2 ,DFish 3 , R Liebmann 2 .1 Thames Histopathology Training School, 2 Kent Cancer Network3 Cellular Pathology Maidstone & Tunbridge Wells NHS TrustIntroduction: Pathology plays an essential role in the assessment of risk,diagnosis, and management of breast cancer. This audit reviews the laboratoryhandling and pathological reporting of 500 breast biopsy specimens acrossKent. High quality and cost effective pathology reports are vital for the deliveryof a fast and accurate diagnostic component to the patient pathway and deliveryof 31/62 day National Cancer wait targets.Method: Consecutive batches of 100 needle core biopsy reports from each ofthe 5 Kent histopathology departments are being retrospectively reviewed. Weexamine adherence to agreed national and local guidelines. Conformity with theminimum dataset of diagnostic information as defined by the Royal College ofPathologists is being investigated. In addition, we perform an analysis ofturnaround times in view of a 4 day target as defined by the Kent CancerNetwork Breast Pathway.Results: The audit results are to be presented. This audit will identify variationsin the handling and pathological reporting of breast biopsy specimens acrossKent. The aim is to identify the most efficient and effective means of providinga high quality diagnostic service and achieving a standardised approach to thehandling and reporting of these specimens. The audit has relevance, not only forBreast Pathology Services, but also Breast Surgical and Radiological Practice.42 Summer Meeting (194 th ) 1–4 July 2008 Scientific Programme