2007 Winter Meeting - London - The Pathological Society of Great ...

O9IDIOPATHIC INFANTILE CORONARY ARTERYCALCIFICATION{P} MN Sheppard 1 , NSabire 2 , YHo 31 Dept. of Histopathology, Royal Brompton and Harefield NHS Trust,Imperial College, London, United Kingdom, 2 Dept. of Histopathology,Hospital for Sick Children,Great Ormond Street, London, UnitedKingdom, 3 Dept of Cardiac Morphology, National Heart and LungInstitute, Imperial College, London, United KingdomIdiopathic calcification of coronary arteries is a rare hereditary condition ofinfancy. Complications include cardiac ischaemia, cardiac failure and systemichypertension. We present three cases who masqueraded as other cardiacdiseases with no indication of the real diagnosis prior to autopsy.5 month old girl presented with respiratory failure and hypertension who diedwithin 24 hours of admission. All the coronary arteries were thick walled withnarrow lumen. The aorta, great vessels and renal arteries also showedthickening of the wall. Histology confirmed calcium in the internal elasticlamina of all vessels.Female aged 2 months who was diagnosed with a large VSD. She diedsuddenly prior to surgery and at autopsy the right coronary artery orifice wasreduced to a pin hole. The coronary arteries had white patches which werecalcified with associated ventricular infarction.11 year old female presented with cardiac failure and was diagnosed as dilatedcardiomyopathy. Two weeks late she died suddenly. Coronary arteries werepatent but were firm with calcification and there was ventricular infarction.This rare condition should always be considered in infants and childrenresenting with hypertension, cardiac failure or sudden death.O10Case report: An unusual case of a primary neuroendocrinetumour of the lung with divergent differentiation presentingwith recurrent pneumonia{P} M Haris 1 ,SOsborne 2 ,SEdward 2 , L Davidson 2 , W Merchant 2 ,IH Chaudhry 21 Department of Respiratory Medicine, North Cheshire Hospitals NHSTrust, Warrington, United Kingdom, 2 Department of Pathology, LeedsGeneral Infirmary, Leeds, United KingdomWe report a case of a 36-year-old man, who presented with 6-month history ofrecurrent chest infections. Flexible Fibreoptic Bronchoscopy and PositronEmission Tomography (PET) / Computed Tomography (CT) confirmed a softtissue mass at the inferior aspect of the right hilum, with marked 18 FFluorodeoxyglucose (FDG) uptake in keeping with malignant etiology. Thepatient underwent resection of the right middle and lower lobe.Histopathology revealed a lobulated multi-nodular endobronchial tumourcomposed of aggregates and single ganglion-like cells set in a neural stromawith a fascicular growth pattern. No immature elements were seen.Immunohistochemistry revealed the stromal component to be positive for S100protein, Neurofilament, and CD56, whilst the ganglion-like cells were positivefor Synatophysin, N52 and chromogranin. GFAP, SMA, TTF-1 and desminwere all negative.The features raise the possibility of a gangliocytic paraganglioma, aganglioneuroma or composite paraganglioma of the lung. The terminology inthe literature is confusing and opens up the debate on how best to classify suchlesions.O11Co-Ordinate Expression and Prognostic Significance ofNuclear Receptor Co-Regulators and Interleukins in HumanBreast Cancer{P} AR Green, S El-Sheikh, EC Paish, IO Ellis, E StylianouUniversity of Nottingham, Nottingham, United KingdomWe investigated associations between cytokines and steroid receptor coregulatorsin breast cancer to identify possible prognostic indicators. Interleukin(IL)-1α, IL-1β, IL-8 and SRC-1/NCOA1, AIB1/NCOA3, SMRT/NCOR2,CBP/p300 expression was assessed using immunohistochemistry in breastcarcinomas (n=130) prepared as tissue microarrays. The targets were correlatedwith each other, clinicopathological variables and patients’ outcome.Associations between the co-ordinate expression of IL-1α, IL-1β, IL-8 and coregulatorsin breast cancer were found, particularly with AIB1/NCOA3.Expression of IL-8 was inversely correlated with oestrogen receptor andprogesterone receptor. Co-regulators CBP/p300 and SMRT/NCOR2 werepositively associated with oestrogen receptor α, β and androgen receptor whilstexpression of AIB1/NCOA3 and SRC-1/NCOA1 were associated with estrogenreceptorβ alone. Both IL-8 and SRC-1/NCOA1 showed a significant positivecorrelation with a good prognosis whilst SRC-1/NCOA1, SMRT/NCOR2 andCBP/p300 were associated with lower histological grade. There was noassociation between expression of interleukins 1 or 8 nor co-regulators withpatients’ outcome or response to endocrine therapy. This study hasdemonstrated associations between cytokine and nuclear receptor co-regulatorexpression suggesting a possible molecular cross-talk between these pathways.Interleukins 1 and 8 may compete for the same co-regulators essential to theregulation of transcription of target genes which may be an important molecularmechanism by which breast cancer tumorigenesis is regulated.O12ALTERED DNA REPAIR AND RESPONSEPROTEIN EXPRESSION IN NON-INVOLVEDCANCER-CONTAINING BREASTS.{P} AJ Batchelder, RA WalkerUniversity of Leicester, Leicester, United KingdomWe have previously identified differences in growth regulation andmyoepithelial cell function of normal breast from cancer-containing breasts.This study investigated expression of proteins implicated in DNA damageresponse and repair in histologically normal tissue from cancerous breasts(NTCCB) and age-matched controls, to determine whether there are anydifferences that could promote breast carcinogenesis.Expression of ATM, BARD1, BRCA1, HSP27 and HSP70 was determined byimmunohistochemistry in 58 NTCCB (cases) and 62 normal tissues fromwomen without cancer (controls). HSP27 expression was significantly greaterin the case group (p=0.001). Extent of immunostaining for ATM and HSP70was similar for both groups. BRCA1 staining was greater in NTCCB fromwomen ≤39 years but was not statistically significantly different. BARD1staining in the case group was lower, but also was not statistically significant.Quantitative RT-PCR was used to compare BRCA1 gene and proteinexpression. Higher gene expression was found in NTCCB, correlating withimmunohistochemical studies.The greater expression of HSP27 may confer a survival advantage to alteredcells due to its anti-apoptotic functions, and is further evidence, along with ourprevious studies, of altered apoptotic regulation in cancer-containing breasts.This may result in an underlying susceptibility to breast tumourigenesis.52 Winter Meeting (191 st ) 3–5 January 2007 Scientific Programme