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

P17Specimen Handling of Screen-Detected Ductal Carcinoma-In-Situ (DCIS) by Surgeons and Pathologists: Could We DoBetter?J Macartney 1 , JSTJ Thomas 2 , SE Pinder 3 , A Hanby 4 , IO Ellis 5 ,K Clements 6 , G Lawrence 6 , H Bishop 71 Pathology Department, University Hospital, Coventry, 2 PathologyDepartment, Western General Hospital, Edinburgh, 3 Department ofAcademic Oncology, Guy's Hospital, London, 4 Pathology Department,St James's University Hospital, Leeds, 5 Pathology Department, CityHospital, Nottingham, 6 West Midlands Cancer Intelligence Unit,University of Birmingham, 7 Breast Unit, Royal Bolton Hospital, BoltonThe management of DCIS requires close cooperation between, surgeon,pathologist and radiologist in order to identify the size and surgical clearance ofDCIS accurately and optimise the effectiveness of subsequent therapy. We haveanalysed results from 2099 cases of screen-detected DCIS recorded in theSloane database of screen-detected DCIS to assess current practice.70.6% had 1 operation (wide local excision (WLE) or mastectomy), and 2.8%had 3 or more operations. In 12% of WLEs specimen orientation markers wereeither absent or uninterpretable. Whereas 96% cases had specimen radiology aspart of the surgical procedure, only 31.5% had subsequent specimen radiologyundertaken by the pathologist and practice in individual laboratories rangedfrom 0% specimens imaged to 100% specimens imaged. Cases that were notimaged by a pathologist had significantly fewer blocks of tissues sampled andthe size of the DCIS was probably underestimated in some of these cases.11.3% of local excisions specimens undergoing only 1 therapeutic excision hadradial surgical margins of less than 1mm, 27% cases had radial margins of 1.1-5mm and 50.8% cases had radial margins of >5mm.Conclusion: The results suggest that there is still considerable scope forimproved specimen handling by surgeons and pathologists and currenttherapeutic decisions may be based on less than optimal information in asignificant proportion of cases.P19Successful oxytocin supported harvesting of nipple fluidKP Suijkerbuijk* 1 , E Van Der Wall# 1 , PJ Van Diest* 11 University Medical Centre Utrecht, *Dept of Pathology and #Division ofInternal Medicine and Dermatology,The NetherlandsBackground: New non-invasive breast cancer screening modalities are required.Nipple fluid, that contains breast epithelial cells, is produced in small amountsin the breast ducts of non-lactating women and can be collected by non-invasivevacuum-aspiration. Previous studies failed to obtain nipple fluid in aconsiderable proportion of women.Aim: feasibility of performing (intranasal) oxytocin supported nipple aspiration(by vacuum) was assessed on 67 healthy female volunteers, age 18-60, 12%postmenopausal.Results: Nipple aspiration was successful in 63/67 women (94%); in 13 women(19%) unilaterally and in 50 (75%) bilaterally. The only predictor for fluidyielding during aspiration was history of nipple discharge (p100 ?l, containing 50-200 ng/?l DNA,which showed to be largely enough for performing a quantitative methylationspecific PCR for multiple genes. The procedure was very well endured. Meandiscomfort-rating during different stages of the procedure was 1.3 (on a 0-10scale), compared to 1.9 for breastfeeding and 4.3 for mammography.Conclusion: Oxytocin supported nipple aspiration provides a valuable tool foraccessing mammary epithelium, providing sufficient DNA for a broad spectrumof analysis in the large majority of women.P18Is Acinic Cell Carcinoma a Variant of Secretory Carcinoma?JS Reis-Filho 1 , R Natrajan 1 , R Vatcheva 1 , MB Lambros 1 ,C Marchio 1 , B Mahler-Araujo 1 ,CPaish 2 ,ZHodi 2 ,VEusebi 3 ,IO Ellis 21 Molecular Pathology Laboratory, The Breakthrough Breast CancerResearch Centre, Institute of Cancer Research, London, 2 MolecularMedical Sciences, University of Nottingham and Department ofHistopathology, Nottingham City Hospital NHS Trust, Hucknall Road,Nottingham, 3 Department of Anatomical Pathology, Ospedalle Belaria,University of Bologna, Bologna, ItalySecretory carcinomas (SCs) and acinic cell carcinomas (ACCs) of the breast arerare, low grade malignancies that preferentially affect young female patients.These lesions are reported to have overlapping morphological andimmunohistochemical features, which have led some to propose that theywould be two morphological variants of the same entity. It has beendemonstrated that SCs of the breast consistently harbour the t(12;15)ETV6-NTRK3 translocation. We hypothesised that if ACCs were variants of SCs, itwould be reasonable to expect that ACCs would also harbour ETV6 generearrangements. Using the ETV6 FISH DNA Probe Split Signal (Dako), weinvestigated the presence of ETV6 rearrangements in 3 SCs and 6 ACCs. Caseswere considered as harbouring an ETV6 gene rearrangement if >10% nucleidisplayed ‘split apart signals’ (i.e. red and green signals were separated by adistance greater than the size of two hybridisation signals). Whilst the three SCsdisplayed ETV6 split apart signals in >10% of the neoplastic cells, no ACCshowed any definite evidence of ETV6 gene rearrangement. Using in-houseprobes to investigate the presence of fusion between ETV6-NTRK3, weconfirmed the presence of the t(12;15) in SCs, but not in ACCs. Based on thelack of ETV6 rearrangements in ACCs, our results strongly support the conceptthat SCs and ACCs are distinct entities and should be recorded separately inbreast cancer taxonomy schemes.P20Expression of Estrogen Receptor Beta is Regulated byAlternative 5'-Untranslated Regions in Breast CarcinogenesisLSmith 1 , MB Peter 1 , ET Verghese 1 ,VSpeirs 1 , TA Hughes 11 University of LeedsEstrogen receptor (ER) expression is a key determinant of breast tumourbehaviour, although the role of ER, unlike the well-studied ER, remainsuncertain. This is partly because analyses have been confused by discrepanciesbetween ER mRNA and protein levels. We demonstrate that alternative 5’-untranslated regions (5’UTRs) allow differential post-transcriptional regulationof ER expression, which may be responsible for non-concordance of mRNAand protein and could provide an important level of modulation of ER activity.We studied three alternative ER 5’UTRs that are produced from alternativepromoters and/or transcriptional start sites. We show that these ER 5’UTRsare differentially expressed between normal and tumour tissues. Furthermore,each 5’UTR has profound and differential influences on mRNA translationalefficiency and stability. We investigated sequence determinants of these effectsand influences of single nucleotide polymorphisms. We also demonstrate thateach 5’UTR is preferentially associated with mRNA variants containingdifferent 3’ splicing patterns, which code for different functions. Finally, usinga 442-case breast cancer TMA, we identified a positive correlation betweenexpression of ER1 and eIF4E, a known regulator of 5’UTR function, therebysuggesting a role for cross-talk between 5’UTRs and cellular factors in definingER expression.In conclusion, post-transcriptional regulation plays an important role indetermining ER expression and function. This may have an overall influenceon ER activity and could have important implications on breast cancer biologyand treatment.36 Summer Meeting (194 th ) 1–4 July 2008 Scientific Programme