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

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13 Expression Of MHC Class I And II In Gastric Carcinomas N.O.S. In Relation To T-Cell Infiltrate: Differences Between Epstein Barr Virus Positive And Negative Tumours E. Bloemena 1 , J. van Beek 1 , A. Snel 1 , W. Vos 1 , C.J.H. van de Velde 2 , E. Klein Kranenbarg 2 , C.J.L. Meijer 1 1 Dept of Pathology,VU University Medical Centre, Amsterdam, Netherlands, 2 Dept of Surgery, Leiden University Medical Centre, Leiden, Netherlands Epstein Barr Virus (EBV) is associated with several benign and malignant diseases, amongst which gastric adenocarcinomas (GCs). We have previously demonstrated, in a large Dutch cohort of GCs, collected between 1989 and 1993 in the course of a large randomised multicenter surgical study (D1D2), that the incidence of EBV-positive GCs was 7.2% (41 of 566 patients). Remarkably, EBV-associated tumours had a significantly lower frequency of lymph node metastases (63.4% N0) compared to EBV-negative tumours (38,7% N0) (P=0.034). In the present study we investigated whether the lower frequency of lymph node metastases could be attributed to differences in expression of MHC molecules and/or T cell infiltrate between EBV-positive and negative tumours, reflecting possible immune stimulation by the presence of foreign, virus related antigens. Formalin-fixed, paraffin embedded material of primary tumours (EBV+:n=20; EBV-: n=28) were stained with the antibodies HCA2, HC10 (MHC I), beta-2-microglobulin (MHCI), LN3 (MHCII), CD3 (pan T), CD4, CD8, and granzymB7. Results were scored semiquantatively. EBV-associated GCs were significantly more often positive for MHC cl II (EBVpos= 12/20 vs EBVneg=8/28 ) (P=0.029), had a more extensive T cell infiltrate (P= 0.0001), with a higher relative contribution of CD8+ cells (P=0.022) of which a higher percentage displayed an activated (granzymB positive) phenotype (P=0.028).These results demonstrate that in EBV bearing gastric carcinomas, in contrast to EBV negative tumours, a cytotoxic immune response is found, presumably directed against EBV related antigens on the neoplastic cells. 14 Bone Marrow Cells Contribute To Vascular Lineages In Colitis M Brittan 1 , V Chance 2 , T Hunt 1 , RE Jeffery 1 , G Elia 1 , R Poulsom 1 , MR Alison 3 , TT MacDonald 2 , NA Wright 4 1 Histopathology Unit, Cancer Research UK, London, United Kingdom, 2 Division of Infection, Inflammation and Repair, University of Southampton, Southampton, United Kingdom, 3 Dept. Histopathology, Imperial College, London, United Kingdom, 4 Dept. Histopathology, Bart's and The London Hospitals, London, United Kingdom Introduction: We report blood vessels containing bone marrow (BM)-derived smooth muscle (SM) cells and endothelial cells in the inflamed mouse colon, highlighting the role of BM in vasculogenesis in tissue regeneration. Methods: Lethally-irradiated female mice were rescued by a BM transplant from male donors. Colitis was induced by intrarectal injection of trinitrobenzene sulphonic acid (TNBS) 6 weeks post-transplant, and colons were analysed 1-14 days post- TNBS. In situ hybridisation for Y chromosome was combined with immunohistochemistry for specific antigens e.g., alpha smooth muscle actin [SMA], ICAM-1, PECAM-1, and F4/80, to identify transplanted cells and determine their phenotype. Results: Many venules and arterioles, delineated by morphological criteria, were identified in inflamed colons, and contained vascular SM and endothelial cells that displayed a Y chromosome and were thus derived from the transplanted BM. Vessels were observed, albeit rarely, that were composed entirely of cells of BM origin, indicative of neovasculogenesis by BM. Vascular SM lining cells were immunoreactive for SMA, and endothelial cells expressed ICAM-1 and PECAM-1 antigens. Importantly, cells were present in vessels that were BM-derived, but did not express the mouse macrophage marker, F4/80. In ethanol-treated control colons, BM contributed to 4.2% of vascular SM cells, which increased significantly to 26.8% in colitis. Conclusions: We believe this is the first report of BM regulation of vasculogenesis in colitis. It is possible that BM cells engraft within existing venules and promote regeneration by angiogenesis, or alternatively, that BM cells form entire new venules by neovasculogenesis. This demonstrates the importance of BM in tissue repair in diseases such as colitis. 15 Array-CGH Demonstrates Chromosome Aberrations In Both Near-Diploid And Microsatellite Unstable Colorectal Cancers G Poulogiannis 1 , K Ichimura 1 , NG Miller 1 , IM Frayling 2 , RG Morris 3 , DJ Harrison 3 , VP Collins 1 , A Ibrahim 1 , AH Wyllie 1 , MJ Arends 1 1 Department of Pathology, University of Cambridge, Cambridge, United Kingdom, 2 Institute of Medical Genetics, University Hospital of Wales, Cardiff, United Kingdom, 3 Pathology, School of Molecular and Clinical Medicine, University of Edinburgh, Edinburgh, United Kingdom Previous analyses of colorectal cancer have shown at least two patterns of genomic abnormality with differing prognoses. Those with chromosomal instability, identifiable as aneuploidy, and those with microsatellite instability (usually near-diploid), which show inactivation of the DNA mismatch repair (MMR) system. Recently, a third category of colorectal cancers has emerged that are microsatellite stable and near-diploid. To further define these categories we applied array-based comparative genomic hybridisation (array-CGH) to examples of each, preselected from a series of 80 left-sided colorectal adenocarcinomas. Aneuploid tumours were distinguished from near-diploid by flow cytometric assessment of DNA index. MMR status was determined by hMLH1 & hMSH2 immunohistochemistry and microsatellite stability (MSS) or instability (MSI) at 10 microsatellite loci. We found that 26 of these tumours (32.5%) were near-diploid (single modal DNA index between 0.8 and 1.2) and MSS, whilst 38 (47.5%) were aneuploid and MSS, 10 (12.5%) were aneuploid and MSI+ and 6 (7.5%) were near-diploid and MSI+. Array-CGH revealed the presence of DNA copy number changes in all tumour categories, but there were two striking findings. First, several tumours in the near-diploid & MSS group showed the same pattern of common changes as has already been described in the aneuploid & MSS group (7+, 8p-, 8q+, 13+, 17p-, 18q-, 20+), but without the many other “background” chromosome imbalances. Second, near-diploid tumours, whether MSS or MSI+, often showed small regions of amplification or deletion. We conclude that genome-wide high resolution array-based analyses of colorectal cancers reveal a much more complex, but informative picture of genomic alterations in colorectal cancer. 16 Abdominoperineal Resection For Rectal Carcinoma; The Pathologists’ View I.D. Nagtegaal 1 , C.J.H. van de Velde 2 , C.A.M. Marijnen 2 , J.H.J. van Krieken 1 , P. Quirke 3 1 UMC St Radboud, Nijmegen, Netherlands, 2 LUMC, Leiden, Netherlands, 3 Academic Unit of Pathology, Leeds, United Kingdom Abdominoperineal resection (APR) is in general indicated for low rectal cancer (i.e. located less than 5 cm from the anal verge). Although in recent years the prognosis of rectal carcinoma patients in general has been greatly improved, results for lower rectal cancer are still disappointing. Moreover, the application of pre-operative short-term radiotherapy in this group of tumours, has no significant effect on prognosis. We studied a trial population of rectal cancer patients (n = 1530), in which 455 patients (29.7%) were operated upon using a Total Mesorectal Excision in combination with an APR. Half of the patients were irradiated (preoperative 5 x 5 Gy). Outcome measures were both prognosis and quality of surgery. Quality of surgery was measured indirectly, by using circumferential margin involvement, and directly using photographs of the specimen. The mesorectum was graded as previously described, and for the grading of the anal canal a new system has been developed; which has been applied by two pathologists. In the APR group more CRM were positive compared to low anterior patients (28.8% versus 13.5%, p < 0.001). When prognosis was corrected for margin status, no differences were observed in the CRM negative group, but in the CRM positive group prognosis of APR patients was still worse (30.7% vs. 17.7%). The high number of positive margins in the APR group are at least partly caused by the incomplete resection (i.e. perforation or missing areas of the muscularis propria): 40-48%. The scoring of the quality of surgery in the anal canal did not show any independent prognostic value, but this evaluation identifies a major cause of local recurrence that may be avoided by wider excision or chemoradiotherapy. 30
17 Expression Of Epidermal Growth Factor Receptor And c-erb- B2 In Colonic Neoplasms of Familial Adenomatous Polyposis Patients - Are They Therapeutic Targets? M. El-Bahrawy 1 , D. Horncastle 1 , N. El-Masry 2 , I. Talbot 3 , I. Tomlinson 4 , R. Poulsom 4 , M. Alison 1 1 Hammersmith Hospital, London, United Kingdom, 2 Charing Cross Hospital, London, United Kingdom, 3 St. Mark's Hospital, London, United Kingdom, 4 Cancer Research UK, London, United Kingdom The expression of epidermal growth factor receptor (EGFR) and c-erb-B2 are reported to be poor prognostic factors in sporadic colorectal carcinoma, and there are currently clinical trials targeting EGFR. The aim of this study was to investigate the expression of EGFR and c-erb-B2 in normal mucosa, adenomas and carcinomas from familial adenomatous polyposis coli (FAP) patients, to explore the role of EGFR in the adenomacarcinoma sequence. The expression of EGFR and c-erb-B2 was studied by immunohistochemistry in normal mucosa, adenomas and carcinomas from 15 FAP patients. 165 adenomas and 15 carcinomas with the adjacent non-neoplastic mucosa were studied. The non-neoplastic mucosa showed cytoplasmic expression and weak membranous expression of EGFR in the basolateral aspects of the cell. Of the adenomas, 64% showed weak cytoplasmic staining, 18% showed cytoplasmic and membranous staining and 18% were negative. In adenocarcinomas 47% showed cytoplasmic staining, 7% showed cytoplasmic and membranous staining, while 47% were negative. In terms of c-erb-B2, weak cytoplasmic expression was seen focally in the surface epithelium of the non-neoplastic mucosa and of 17% of adenomas while all carcinomas were negative. This is the first study investigating the expression of these two receptors in both adenomas and carcinomas from FAP patients. The study shows that c-erb-B2 is not upregulated in tumours of FAP patients, while EGFR appears to be upregulated in a considerable percentage of both adenomas and carcinomas. We conclude that EGFR, but not c-erb-B2, may be a target for therapeutic intervention in FAP patients. 18 Tumour Suppressor Gene Methylation Status in Colorectal Adenomas: Relation to Point Gene Mutation and Chromosomal Abnormality H Judson , A Stewart , A Leslie , NR Pratt , DU Baty , RJC Steele , FA Carey University of Dundee, Dundee, United Kingdom Epigenetic mechanisms in carcinogenesis may have a significant role in development of colorectal cancer. To investigate this phenomenon in earlystage disease promoter methylation status in the tumour suppressor genes APC, MGMT, h-MLH1, p14 and p16 was investigated in 78 colorectal adenomas which had previously been characterised for mutations of APC, K-ras and p53 genes and for chromosomal abnormality by comparative genomic hybridisation (CGH). APC hypermethylation was seen in 51 tumours (65.4%). APC showed either methylation or mutation in 65 lesions (83.3%). MGMT methylation was detected in 38 cases (48.7%). Adenomas with this abnormality showed a significantly lower number of chromosomal changes by CGH (p
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 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 42 and 43: 61 Expression Of The Transcription
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
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213 Microarray Based Comparative Ge
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221 IMMUNOHISTOCHEMISTRY (IHC) ON B
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