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

O13O14Abstract withdrawnCISH, a simple, robust and cost-efficient test for HER2 status{P} S Di Palma, N Collins, M Kissin, M CookRoyal Surrey County Hospital, Guildford, Surrey, United KingdomHuman epidermal growth factor receptor 2 (HER2) is important in signaltransduction in both normal and abnormal cells. HER2 protein overexpressionand/or gene amplification is detected in approximately 20% breast tumours, isassociated with an aggressive phenotype and is predictive of response totrastuzumab therapy. Here we evaluate the robustness, utility and costeffectivenessof a chromogenic in situ hybridisation (CISH)-based assay foranalysing HER2 status routinely. Formalin fixed paraffin embedded sampleswere examined using a CISH assay, analysed by light microscopy and scoredaccording to the manufacturers protocol. The results from 161 of the sampleswere compared to results obtained using the immunohistochemistry (IHC)DAKO HercepTest and FISH PathVysion analyses that had been performed inexternal reference laboratories. 20.8% samples were found to haveamplification of the HER2 gene. There was 100% concordance between CISHand FISH but only 95% concordance between CISH and IHC. 1 IHC1+ samplewas found by CISH to have a high level amplification and 7 IHC 3+ sampleswere found to be HER2 non-amplified. Using CISH in place of IHC and FISHwas approximately 25% more cost effective per sample. It is concluded thatCISH is as accurate as FISH. It is a simple but robust assay for HER2evaluation that can be easily and cost-effectively integrated into the routineworkload of a pathology laboratory, the level of amplification can be reportedand it involves the pathologist in the diagnosis.O15Low level or loss of detection of acetylated Lys16 andtrimethylated Lys20 of Histone H4 and its Effect on theMalignant Phenotype and Patient Outcome in BreastCarcinoma{P} SE El Sheikh 1 , AR Green 1 , DM Heery 2 , IO Ellis 11 Department of Pathology ,Nottingham University Hospital, Nottingham,United Kingdom, 2 School of Pharmacy, Nottingham University,Nottingham, United KingdomHistone modification is recognised to play a key role in control of geneexpression and chromatin structure in normal cells, but whether or how thesemodifications are altered in cancer are unclear. Monoacytelated lys16 andtrimethylated lys20 at H4 have been found to be lost in breast cancer cells.However the clinical significance of this aberration is unknown. In this studywe assessed post-transitional modification of H4 at these two residues in a wellcharacterisedseries of breast carcinomas (n=880) with long term follow-upusing immunohistochemistry and tissue microarray technology and the resultwas correlated with the clinicopathological variable and patient outcome.Low level or loss of detection of acetylated/trimethylated H4 was observed inmedullary type carcinoma and was associated with high grade, poorNottingham prognostic index, larger tumour size, development of distantmetastasis, negative (oestrogen receptor, luminal cytokeratines) and positivebasal cytokeratines. Survival analyses showed low/loss of detection of thesemodifications is associated with shorter overall survival and shorter disease freeinterval.This work demonstrates that, low level or loss of detection of Monoacytelatedlys16 and trimethylated lys20 at histone H4 may play a role in breast cancerdevelopment and is associated with an aggressive phenotype and poor patientoutcome.O16Expression of BRCA1 protein in breast and ovarian cancersand its prognostic significance{P} E Rakha 1 ,MKandil 2 , S El-Shaikh1 1 , I Ellis 11 Nottingham University, Nottingham, United Kingdom, 2 HistopathologyDepartment, Menoufia, EgyptThe purpose of the current study was to examine the expression and localizationof BRCA1 protein, and to assess its prognostic value, in a well-characterizedseries of unselected breast and ovarian carcinomas. Methods: We haveexamined BRCA1 in series of invasive breast carcinoma (1600 cases, usingtissue microarray), and ovarian tumours (whole tissue sections)immunohistochemically, to evaluate its expression pattern and to correlate thiswith clinicopathologic variables and patients outcome. Results: In the breast,altered nuclear expression (absent or reduced) was observed in 801 cases (54%)and cytoplasmic expression was detected in 541 breast cancers (36.6 %).Altered nuclear BRCA1 expression was more frequent in duct/no special typeand medullary-like carcinomas and less frequent in lobular and tubular mixedcarcinomas. It showed an associated with high tumour grade, advanced LNstage, larger size, vascular invasion, negative ER, PgR and androgen andpositive p53, P-cadherin and basal CKs expression. Reduced or absent nuclearBRCA1 was associated with shorter disease free survival. Cytoplasmicexpression was associated with high grade, larger size, development ofrecurrence, positive p53, P-cadherin, EGFR, HER2 and basal CKs expression.It also showed an inverse association with survival particularly in low grade,small size and ER positive subgroups. In ovarian tumours, altered BRCA1expression was associated with LN disease and high grade tumours.Cytoplasmic and absent nuclear BRCA1 was associated with shorter survival.Conclusion: BRCA1 may play a significant role in the development andprogression of breast and ovarian cancer. IHC assessment of BRCA1expression could provide additional prognostic value that may affect patientmanagement particularly in the well-differentiated breast cancer.Winter Meeting (191 st ) 3–5 January 2007 Scientific Programme53