2004 Summer Meeting - Amsterdam - The Pathological Society of ...

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61 Expression Of The Transcription Factor CTCF In Invasive Breast Cancer: A Candidate Gene Located At 16q22.1 E.A Rakha , C.E Paish , S.E Pinder , I.O Ellis Nottingham, City Hospital, Nottingham University, Nottingham, United Kingdom CTCF is a ubiquitous 11-zinc finger protein that plays a role in gene silencing or activation, chromatin insulation and genomic imprinting. The CTCF gene has been mapped to chromosome band 16q22.1 that shows frequent loss of heterozygosity in breast cancer. Because CTCF targets include TSGs and oncogenes and it has the ability to inhibit cell growth and proliferation, it has been suggested that it may be the target gene at the 16q22.1 especially in ductal tumours. In the present study, tissue microarray technology was used to study the expression pattern of CTCF immunohistochemically in 344 cases of invasive breast carcinoma and its expression was correlated with clinicopathological variables and patient outcome. Expression of CTCF was detected in the cytoplasm and nuclei of the normal parenchymal as well as malignant cells of the breast. In the malignant tissues, no significant loss or decrease of expression was noticed in association with any specific tumour type. There was a significant correlation between nuclear and cytoplasmic expression of CTCF and histological grades; lower expression was associated with grade 3 tumours. Cytoplasmic expression was associated with increased tumour size and with the presence of vascular invasion. However, no association was found between CTCF expression and tumour type, lymph node stage, oestrogen receptor expression or patient outcome. Conclusion: The current results show that CTCF, although it may play a role in breast carcinogenesis, is unlikely to be the TSG targeted by the 16q22.1 loss in breast cancer and thus another gene or genes at this region remain to be identified. 62 Expression and co-expression of the Epidermal Growth Factor Receptor [EGFR] family members in invasive breast cancer DM Abd El-Rehim , S Pinder , IO Ellis Department of Histopathology, University of Nottingham, Nottingham, United Kingdom We have evaluated more than 1500 cases of invasive breast carcinoma immunohistochemically using tissue microarray technology to examine the expression of EGFR family receptor proteins. Overall, 20.1% and 31.8% of cases were positive for EGFR and c-erbB-2 respectively and 45% and 45.1% of tumors over-expressed for c-erbB-3 and c-erbB-4 respectively. The expression of either EGFR or c-erbB-2 was associated with bad prognostic features and with poor outcome. c-erbB-2 had an independent prognostic effect on overall and disease free survival in all cases as well as in the sub-set of breast carcinoma patients with nodal metastases. Cases were stratified according to receptors co-expression into distinct groups with different receptor positive combinations. Patients whose tumors coexpressed c-erbB-2 and c-erbB-3, as well as those whose tumors co-expressed EGFR, c-erbB-2 and c-erbB-4 showed an unfavorable outcome compared with other groups, whilst combined c-erbB-3 and c-erbB-4 expression was associated with a better outcome. Additionally, we found a significant association between c-erbB-4 homodimer expressing tumors and better disease free survival. In contrast, patients with c-erbB-2 homodimer expressing tumors had a significant poorer disease free survival compared with other cases. These data imply that the combined profile expression patterns of the four receptor family members together provides more accurate information on the tumour behaviour than studying the expression of each receptor in isolation. 63 Expression of luminal and basal cytokeratins in human breast cancer DM Abd El-Rehim , S Pinder , IO Ellis Department of Histopathology, University of Nottingham, Nottingham, United Kingdom We have examined basal and luminal cell cytokeratin expression in 1944 cases of invasive breast carcinoma, using tissue microarray technology, to determine the frequency of expression of each cytokeratin subtype, their relationships and prognostic relevance, if any. Expression was determined by immunocytochemistry staining using antibodies to the luminal cytokeratins 7/8, 18 and 19 and the basal cytokeratins 5/6 and 14. Additionally, assessment of alpha smooth muscle actin and estrogen receptor status was performed. The vast majority of the cases showed positivity for ck 7/8, 18 and 19 indicating a differentiated glandular phenotype, a finding associated with good prognosis, ER positivity and older patient age. In contrast, basal marker expression was significantly related to poor prognosis, ER negativity and younger patient age. Multivariate analysis showed that ck 5/6 was an independent indicator for relapse free interval. We were able to subgroup the cases into four distinct phenotype categories [luminal, mixed luminal/basal, basal and null], which had significant differences in relation to the biological features and the clinical course of the disease. Tumors classified as expressing a basal phenotype [the combined luminal plus basal and the pure basal] were in a poor prognostic subgroup, typically ER negative in most cases. These findings provide further evidence that breast cancer has distinct cellular differentiation subclasses that have both biological and clinical relevance. 64 Effect of Assay Sensitivity on ER Negativity Rate AG Douglas-Jones , JM Morgan , S Wozniac , S Hughes , S Thomas , S Rivett , M McKenny , B Jasani Department of Pathology, University of Wales College of Medicine, Cardiff, United Kingdom An audit of 2,595 consecutive routine ER results determined ER negative rates at 3-month intervals. Sensitivity of the assay was monitored by semiquantitative assessment (H score) of control sections. The H scores of selected sub-groups allowed modeling of the whole set of results to show the relationship between assay sensitivity and ER negativity rate. The ER negativity rate varied between 7.5 and 21% and assay sensitivity varied by 58 H score points about a mean of 116 (16%). Modeling showed that this range of assay sensitivity would translate into a change in ER negativity rate of 14%. The model also shows how alteration of the threshold for ER positivity changes ER negative rates. Changes in ER assay sensitivity can account for the differences in ER negativity rate observed in routine clinical practice. 42
65 Multiple Papillomatosis of the Breast: Charactarisation of 20 Cases A G Douglas-Jones , M Khan Department of Pathology, University of Wales College of Medicine, Cardiff, United Kingdom In order to characterise the entity, twenty cases of multiple papillomatosis (greater than 5 papillomas) of the breast was studied. The mean age of the patients was 55. Four patients (20%) had a diagnostic procedure only and 16 were treated, 7 (35%) had a wide local excision and 9 (45%) underwent mastectomy. Two cases (10%) were bilateral. The mean number of papillomas per case was 47 (range 5-140) and the papillomas over all cases had a mean diameter of 2mm (range 0.1-11.5mm). In individual cases the mean size of papillomas ranged between 0.6 and 5mm. In all but one case there were other associated proliferative breast lesions and in half the cases papillomas only accounted for 50% of the lesions present. All the cases contained epithelial hyperplasia (epithelium more than 2 cells thick) and in the different cases between 4.7% and 68.9% of lesions showed epithelial hyperplasia of usual type. 15 (75%) of cases showed atypical ductal hyperplasia (ADH) in the different cases 4.5-38% of lesions showed ADH. Ten (50%) of cases contained DCIS and in the different cases between 5-45% of the lesions were DCIS. Multiple papillomatosis shows great variation in the numbers of papillomas present but the individual papillomas are small (less than 5mm). Most cases are associated with other proliferative lesions of the breast. All cases show epithelial proliferation and 50% contain foci of DCIS. 66 Signal transduction and cell cycle regulation by the breast myoepithelial cells JCA Luckett , JA Shaw , JL Jones , RA Walker University of leicester, leicester, United Kingdom Cellular cross talk is an important mechanism for the homeostatic control within tissues. The breast lobular compartment is made up of two main cell types, with a myoepithelial cells layer surrounding the luminal cells. This layer of cells is lost on the progression from DCIS to invasive breast cancer. To examine the role of myoepithelial cells in the control of tumour progression a non-contact tissue culture model has been developed. T47D breast cancer cells grown in either 2D and 3D Matrigel in the presence of myoepithelial cells have demonstrated a reduction in proliferation rate and an increase in apoptosis rate. This suggests a paracrine influence of the myoepithelial cells on the T47D cells. Aim: To dissect this paracrine mechanism by looking at key signalling cascades Pi3K/Akt and ERK pathways. T47D cells were grown in myoepithelial conditioned media (myocm) for 6hr, 2 and 7 days in both 2D and 3D models. The effect of myocm on proliferation and apoptosis was confirmed for both time points and this corresponds to changes in phosphorylation status of ERK1/2 and pAKT. However no differences were found at 6 hrs suggesting an indirect effect on cell cycle regulation in the T47D cells. 67 Study of the Potential Predictive Factors of Response of Breast Cancer to Chemotherapy AR HINNIS , JCA Luckett , RA Walker University of Leicester, Breast Cancer Research Unit, Leicester, United Kingdom Chemotherapy is used in the management of breast cancer, either neo-adjuvant or adjuvant, selection being based on pathological features such as size, node status and grade. The aim of this study was to determine whether biological features of breast cancer could provide additional information about the response to chemotherapy. 115 breast cancer patients who had received adjuvant (100) or neo-adjuvant (15) treatment and had died from the disease were studied. Immunohistochemistry was used to assess p53 and phosphorylated p53, apoptotic index (M30), proliferation index (MIB-1), apoptotic proteins bcl-2 and bax, inhibitors of apoptosis proteins Survivin and XIAP, checkpoint kinase 2 (ChK2), and p21 waf-1 . The expression was correlated with tumour size, type, grade, and lymph node status and with the duration of survival. P53 was detected in 38.5%, with phosphorylated p53 in 26.0%. P21 waf-1 was in 25.0%, ChK2 in 69.2% and bcl-2 in 67.3% and all showed a significantly inverse relationship with p53. Survivin (67.6% cases positive) significantly correlated with the presence of p53 and high proliferation. There was a relationship between the absence of phosphorylated p53, low proliferation and lack of Survivin with duration of survival greater than three years. These markers may aid in the selection of patients who would benefit from chemotherapy. 68 Oestrogen Receptor Assays in Breast Cancer : Correlation Between Core Biopsies and Resection Specimens AD Graham , J Loane Western General Hospital, Edinburgh, United Kingdom Immunohistochemical oestrogen receptor (ER) assays were performed on the initial diagnostic core biopsy and the subsequent resection specimen in 86 consecutive cases of invasive breast cancer, 27 treated by mastectomy and 59 by wide local excision (WLE). ER expression was assessed, independently, by a consultant pathologist, using the Quick Score. This places each specimen into one of 4 prognostic categories – negative, weakly positive, moderately positive or strongly positive. These categories correlate well with response to antioestrogen chemotherapy. Categorisation was then compared, both in terms of ‘exact’ agreement (same category score for both core and resection specimen) and ‘clinically relevant’ agreement (ER positive or ER negative). The latter dictates whether anti-oestrogen chemotherapy is indicated. Overall there was exact agreement between the core biopsy and the resection specimen in 68/86 cases (79%) and clinically relevant agreement in 79/86 cases (92%). The mastectomies showed slightly lower agreement than WLE specimens [exact agreement 20/27 vs 48/59 (74% vs 81%); clinically relevant agreement 24/27 vs 55/59 (89% vs 93%)]. This large study indicates that ER status in breast cancer can, in most cases, be accurately assessed on the initial diagnostic core biopsy. The small possibility of a ‘false negative’ result, however, suggests that, following a negative core, it may be prudent to repeat ER assessment on the resection specimen. 43
Page 1 and 2: JOINT MEETING of the Pathological S
Page 3 and 4: Scientific Programme FEATURED TOPIC
Page 5 and 6: Scientific Programme GUEST LECTURES
Page 7 and 8: Scientific Programme TRAVEL (contin
Page 9 and 10: Scientific Programme AMSTERDAM PUBL
Page 11 and 12: Scientific Programme Summary Progra
Page 13 and 14: Scientific Programme Summary Progra
Page 15 and 16: Scientific Programme Detailed Progr
Page 25: Scientific Programme Abstracts 25
Page 28 and 29: 5 Melanoma suppressor responses ind
Page 30 and 31: 13 Expression Of MHC Class I And II
Page 32 and 33: 21 Immunohistochemical Subtyping Of
Page 34 and 35: 29 Regional Quality Control by path
Page 36 and 37: 37 Nuclear Morphometry, Immortaliza
Page 38 and 39: 45 Dietary Fibre Accelerates Polyp
Page 40 and 41: 53 Intestinal Tumourigenesis : Navi
Page 44 and 45: 69 Id2 expression is inversely corr
Page 46 and 47: 77 A Study of Insitu Hybridisation
Page 48 and 49: 85 Is There Agreement Between IMF-D
Page 50 and 51: 93 Recruiting Donors for Autopsy-ba
Page 52 and 53: 101 Workload Implications of Case R
Page 54 and 55: 109 Proposal for a Peer Standardise
Page 56 and 57: 117 Expression of hTERT in gastroin
Page 58 and 59: 125 Assessing Inter-observer Variat
Page 60 and 61: 133 Beta-catenin Expression In Gast
Page 62 and 63: 141 Infertile Males - Who Should Be
Page 64 and 65: 149 Papillary Mucinous Adenocarcino
Page 66 and 67: 157 Oxaliplatin Toxicity In The Liv
Page 68 and 69: 165 The Association Between Early G
Page 70 and 71: 173 Cardiac abnormalities in a paed
Page 72 and 73: 181 Intraocular Ectopic Ependymoma
Page 74 and 75: 189 The Expression of S100A6 Protei
Page 76 and 77: 197 TSLC1 Is A Tumor Suppressor And
Page 78 and 79: 205 Wnt Expression In Colonic Subep
Page 80 and 81: 213 Microarray Based Comparative Ge
Page 82: 221 IMMUNOHISTOCHEMISTRY (IHC) ON B

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