S2021

Clinical and Endoscopic Analysis of Primary T Cell Lymphoma of theGastrointestinal Tract According to Pathology and EBV StatusDo Hoon Kim, Seung-Jae Myung, Jeong-Sik Byeon, Seunghyun Kwon, Byunggyu Kim,Soon Man Yoon, Mi Young Do, Byong Duk Ye, Ho June Song, Hwoon-Yong Jung, Suk-Kyun Yang, Jin-Ho Kim

Background:Primary gastrointestinal(GI) T-cell lymphomas are rare tumors and mostlyreported from the East. The aims of this study were to determine the clinical and endoscopicfeatures of primary GI T cell lymphoma, with special emphasis on the pathologic classification,and to elucidate the correlation between Estein-Barr virus (EBV)/ T-cell receptor generearrangement (TCR) status and prognosis of this disease. Patients and Methods:35 casesof primary GI T cell lymphomas that satisfied Dawson's criteria were enrolled. The meanage at the time of diagnosis was 47.3 years (range 27 - 70), and the male:female ratio was24:11. The 38 lesions from 35 patients were analyzed and classified into enteropathy-type(ETCL), NK/T cell (NK/T), peripheral T cell (PTCL), and anaplastic large cell (ALCL). Clinicalcharacteristics, and endoscopic features were analyzed according to these types, and thesurvival analysis was done according to clinical factors and EBV/TCR status. EBV/TCR wasdetermined by in situ hybridization and PCR. Results:The initial presenting symptoms wereabdominal pain (n=18, 35.0%), fever (n=8, 21.0%), gastrointestinal bleeding (n=6, 15.8%),diarrhea (n=4, 10.5%), and soreness (n=2, 5.3%). As for the location, PTCL more commonlyinvolved stomach (7/12, 58.3%) and duodenum (4/12, 33.3%) while ETCL occurred mostfrequently in small intestine (8/13, 61.5%), NK/T involved small (4/11, 36.4%) and largeintestine (5/11, 45.6%) (p<0.05). The stage of disease at diagnosis was less advanced inNK/T than in ETCL and PTCL (p<0.05). Perforation developed more frequently in NK/T(46.2%) and ETCL (46.2%) than in PTCL (0%) (p<0.05). On endoscopy the lesions wereulcerative in 9 (33.4%), ulcerofungative in 7 (25.9%), ulceroinfiltrative in 5 (18.5%), infiltr-ative in 3 (11.1%), superficial/erosive in 2 (7.4%), and fungating in 1 (3.7%). The distributionwas not different according to the pathologic types. The EBV positivity was higher inNK/T than other types (p<0.05). Initial treatment was surgical resection (n=22, 57.9%),chemotherapy (n=15,39.5%), or supportive care (n=1,2.6%). The median survival was 12.1months. The poor prognosis is associated with more advanced stage, small bowel location,and perforation (p<0.05). Perforation was found to be the only independent predictor forthe prognosis by multivariate analysis (p<0.05). Conclusion:Primary GI T cell lymphomashowed characteristic clinical features according to the 4 major pathologic types. The poorprognosis in this disease is associated with more advanced stage, small bowel location, andperforation. EBV is the most prevalent in NK/T cell type and is not affecting the prognosis.

S2022

Co-Expression of Somatostatin and Dopamine Receptors in NeuroendocrineTumours, An Immunohistochemical StudyRajaventhan Srirajaskanthan, Jennifer Watkins, Martyn Caplin

Introduction: Somatostatin receptor expression in neuroendocrine tumours (NET) has beenwell characterised. Somatostatin receptor-2 (SST-2) and somatostatin receptor (SST-5) aremost commonly expressed, with SST-2 being important in identifying response to somatosta-tin analogues. Human dopamine receptor-2 (DA 2) and SST-5 receptor have been shownto hetero-oligomerize to enhance activity in transfected CHO-K1 cells. Quantification ofdopamine receptor-2 and somatostatin receptors mRNA using real time PCR in NET hasrecently been published. Aims: To demonstrate co-expression of dopamine and somatostatinreceptors in NET. Methods: Consecutive samples of formalin-fixed paraffin-embeddedtumour tissue were available from 58 patients (26 male: 32 female) with a histologicallyconfirmed diagnosis of NET. The study population was divided into low grade (well differenti-ated tumour, Ki67 proliferation index <10%) n=32, and intermediate/ high grade tumours(moderately or poorly differentiated, Ki67 proliferation index >10%) n=26. Samples fromall major NET subtypes including: foregut, mid-gut, hindgut, bronchial, paraganglionomaand NETs of unknown primary were studied. Samples were scored as being either positiveor negative. Results: SST-2 expression in low and high grade tumours was 97% and 77%respectively. SST-5 expression in low and high grade tumours was 97% and 85% respectively.DA-2 expression was 88% in low grade tumours and 58% in high grade tumours. All threereceptors were expressed in 66% of cases (81% in low grade and 46% of high grade).Discussion: This study has demonstrated expression of SST-2, SST-5 and DA2 in low gradeand high grade tumours. Pituitary adenomas are known to co-express somatostatin anddopamine receptors. Suppression of growth hormone using a chimeric somatostatin-dopam-ine molecule has been demonstrated in pituitary adenomas In Vitro. NET co-express SSTand DA2 receptors in two thirds of cases, this offers a potential new treatment approachusing combined somatostatin-dopamine agonists.

S2023

Alpha Fetoprotein and Human Chorionic Gonadotrophin-β Are PrognosticTumour Markers in Patients with Neuroendocrine TumoursTahir Shah, Rajaventhan Srirajaskanthan, Maninder Bhogal, Christos Toumpanakis, TimMeyer, Aneesha Noonan, Caroline Witney-Smith, Tejal Amin, Pervinder Bhogal, NiroshanSivathasan, Ben D. Warner, Martyn Caplin

Background: Tumour markers can provide information regarding tumour functionality andtumour burden. Currently serum chromogranin A is the best general tumour marker availablefor neuroendocrine tumour (NET) patients and is known to correlate with tumour burdenand have prognostic value. The role for other tumour markers is less clear. Aim: To determinethe role of serum alpha-fetoprotein (AFP) and human chorionic gonadotrophin beta (hCG-β) as diagnostic and prognostic markers in NETs. Patients and methods: A database containingpatient demographic data plus biochemical, histological including Ki67 proliferation index,and survival data on 360 NET patients was constructed using an excel spreadsheet. Thisdata was statistically assessed, using SPSS statistics package, to determine the utility ofcommonly measured tumour markers with particular emphasis on AFP and hCG-β. Results:AFP and hCG-β were raised in 9.5% and12.3% of patients respectively. AFP levels associated

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strongly and positively with tumour grade, serum CgA, hCG-β levels and worse survival(mean 37.6 v 69 months for AFP-high and control groups respectively; p=0.001). hCG-βlevels also associated strongly and positively with serum CgA, AFP levels and worseningsurvival (mean 48 v 57.3 months for hCG-β high and control groups respectively; p=0.037).Conclusion: Both AFP and hCG-β are elevated in high-grade neuroendocrine tumours witha rapidly progressive course and poorer survival. They both correlate with chromogranin-A levels. Thus AFP and hCG-β are clinically important and should be routinely measured,especially in those with high grade NETs.

S2024

Comparison of 68GA-Octreotate-PET and (111in)-Pentetreotide Scintigraphy(Octreoscantm)-SPECT in Patients with Neuroendocrine TumoursRajaventhan Srirajaskanthan, Jade Soh, Ann-Marie Quigley, Christos Toumpanakis, JohnBuscombe, Martyn Caplin

Introduction: Neuroendocrine tumours (NETs) are a heterogeneous group of tumours thatoften over express somatostatin receptors. NETs can be imaged with scintigraphy usingradiolabelled somatostatin analogues. The current gold standard is Indium-111 pentetreotidescintigraphy (Octreoscan). Positron Emission Tomography (PET) using Gallium-68 Octreot-ate is now available for the imaging of neuroendocrine tumours. Aim: To evaluate thediagnostic value of Gallium-68 Octreotate PET in patients with known or suspected neuroen-docrine tumours. 68Ga-Octreotate PET was compared to conventional scintigraphy withOctreoscan. Methods: 68Ga-Octreotate PET were performed in 80 patients with either knownor suspected neuroendocrine tumours, these patients had all undergone previous imagingwith Octreoscan, plus CT ± MRI. Cross sectional imaging was used to confirm presence oflesions identified from PET or Octreoscan. The cohort of 72 patients with histologicallyproven neuroendocrine tumours comprised: 29 foregut, 30 midgut, 2 hindgut, 3 paragang-lionomas and 8 with unknown primary. The remaining 8 patients were suspected of havinga NET. The scoring was divided into regional groups, encompassing organs (liver, lung,pancreas, gastrointestinal tract, adrenals/kidney/prostate, spleen, ovaries, brain); nodal groups(thoracic, abdominal/ pelvic, mesenteric) and bones (vertebrae, thoracic, pelvis, limb bones,skull. If multiple lesions were seen in one organ/region, for example the liver, it was scoredas 1. Results: Total number of lesions identified in the 80 cases was 154 for 68Ga-OctreotatePET , 70 for Octreoscan, see Table 1. Confirmation of lesions was made by correlation withCT and/ or MRI. In no instance did Octreoscan outperform 68Ga-Octreotate PET in lesiondetection. Whilst there was increased lesion recognition with PET against Octreoscan in allorgans and nodes, this was most marked with identification of bone metastases. Conclusion:Ga-68 Octreotate PET identifies more lesions than Octreoscan. This modality is importantfor identifying patients who would be suitable for treatment with somatostatin analoguesand radionuclide therapy.Table: Areas of uptake identified by Octreoscan, Ga-68 PET and cross-sectional imaging(CT/ MRI)

S2025

Expression of the EGFR Family of Receptors (EGFR, HER-2, HER-3 and HER-4) in Neuroendocrine TumoursRajaventhan Srirajaskanthan, Tahir Shah, Jennifer Watkins, Laura Marelli, Korsa Khan,Martyn Caplin

Introduction: The EGFR family is comprised of four distinct receptors: EFGR, HER-2, HER-3 and HER-4. The EGFR receptors are not only important for the essential roles they playin normal developmental processes, but also for their association with human tumourogen-esis. Aims: In this study we sought to determine the pattern of expression and the prognosticsignificance of EGFR, HER-2, HER-3 and HER-4 in Neuroendocrine Tumours (NET).Methods: Consecutive samples of formalin-fixed paraffin-embedded tumour tissue wereavailable from 81 patients (32 male: 49 female) with a histologically confirmed diagnosisof NET. The study population included all major NET subtypes including: foregut (34cases), mid-gut (33 cases), hindgut (4 cases), paraganglionoma (6 cases) and 4 cases withNETs of unknown primary. Tumours were classified according to their site of origin, levelof differentiation and their initial mitotic index. Immunohistochemical scoring for eachantibody was based on intensity of tumour staining whereby 0= negative, 1= weakly positive,2= moderate, 3= strongly positive. Tumour staining was also scored, whereby, positivestaining was marked as: 1= <25%, 2= 25-75% and 3=>75%. The product of the density ofstaining and the percentage of tumour cells staining positive was used as the histologicalscore, giving final values of 0,1,2,3,4,6,9. Score of ≤2 were classed as negative. Results:EGFR expression was identified in 69 of 81 (85.1%) samples, HER-2 was not expressed inany tissue, HER-3 was expressed in 7 samples (3 pancreatic, 3 paraganglionoma and 1 mid-gut), HER-4 was expressed 74 (91%). EGFR negative tumours were associated with asignificantly worse prognosis than EGFR positive tumours (p= 0.014). There was no signific-ant association between expression of HER-4 or HER-3 and survival. No significant correlationbetween EGFR and HER-4 expression. EGFR and HER-4 were co-expressed in 80% of cases.Discussion: EGFR and HER-4 are significantly expressed in NETs. EGFR and HER-4 sharemany the same ligands, this in part may explain the expression of these two receptors inNETs. The expression of EGFR does not appear to be a negative prognostic indicator.

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