ECP 2023 Abstracts

S110 Virchows Archiv (2023) 483 (Suppl 1):S1–S391 13 Funding: Innovate UK and Bowel Research UK PS-17-026 Alterations in p53, microsatellite stability and lack of MUC5AC expression as molecular features of colorectal carcinoma associated with inflammatory bowel disease E. Musulen*, M. Gené Hijós, M. Cuatrecasas, I. Amat, J.A. Veiga, M.J. Fernández Aceñero, V. Fusté Chimisana, J. Tarragona, I. Jurado, R. Fernández-Victoria, C. Martinez Ciarpaglini, C. Alenda González, C. Zac, P. Ortega de la Obra, M.T. Fernández-Figueras *Pathology Department, Hospital Universitari General de Catalunya- Grupo Quirónsalud, Sant Cugat del Vallès, Barcelona; Institut de Recerca contra la Leucèmia Josep Carreras, Badalona, Barcelona, Spain Background & objectives: Colitis-associated colorectal carcinoma(CAC) occurs in inflammatory bowel disease(IBD) as a result of the "chronic inflammation-dysplasia-cancer" carcinogenesis. Gastric metaplasia (GM) has been described as the initial event of serrated colorectal cancer(CRC) process. The objective is to characterize CAC to explore GM. Methods: A total of 57 CACwere studied from38 (72%) men and 15 (28%) women, aged between 34 and 90 years (mean 62.6), 34 (64%) with UC and 19 (36%) with CD from a series of 53 IBD colectomies with CAC from 14 hospitals. Immunohistochemistry was performed to assess p53 alterations, MSI, and MUC5AC expression as a surrogate for GM. Results: The p53 mut-pattern was found in more than half of the CAC, most frequently stable (MSS) andMUC5AC negative. Only 6 tumours were unstable (MSI-H), with p53 wt-pattern (p=0.010) and MUC5AC positive (p=0.005). MUC5AC staining was more frequently observed in intestinal mucosa, inflamed or with chronic changes, than in CAC, especially in those with p53 wt-pattern and MSS. Conclusion: Based on our results we hypothesize that, as in the ser- rated pathway of CRC, in IBD GM occurs in inflamed mucosa, persists in those with chronic changes and disappears with the acquisition of p53 mutations. We cannot rule out that the group of MSI-H CRC that appear in IBD, with characteristics similar to MSI-H sporadic tumours with MLH1 hypermethylation, are nothing more than serrated pathway CRC that appear in a context of continuous colon injury. This research was funded by Roche through a collaboration agreement for research in the area of Oncology (activity code: SP210830002). PS-17-027 Developing a revised, prognostically significant morphological clas- sification system for gastro-oesophageal adenocarcinoma (EAC) S. N Kalimuthu*, J. Cotton, R. Zyla, F. Allison, Y. Bach, J. Allen, G. Darling, E. Elimova, G. Wilson, J. Yeung *University Health Network, Toronto, Canada Background & objectives: Oesophageal adenocarcinoma (EAC) has a poor prognosis. Methods for stratifying patients into prognostic/treatment- responsive groups are lacking. Presently, the significance of morphologi- cal heterogeneity in these tumours is not understood. We aim to develop a prognostically significant morphological classification for EAC. Methods: All tumour slides were reviewed from 106 patients who under- went resection from 2008 to present. Tumour morphology was quantified by calculating percentage of each pattern per slide and summed across all case slides to determine overall percentage of each morphology. We cat- egorized cases as neoadjuvant-treated or untreated resection specimens and collected survival data for each surgical resection case. Results: In this study, 70 patients (58 male, 12 female; mean age = 59.26 +/- 11.12 years) received neoadjuvant therapy before resection, while 36 patients (29 male, 7 female; age = 66.36 years +/- 11.85 years) did not receive any treatment. Treated cases had a higher aver- age number of slides reviewed (10.13 +/- 7.43 slides) than untreated cases (9.14 +/- 8.57 slides). In untreated cases, 33% (12/36) showed three [WG1]or more morphologies comprising over 10% of the tumour area compared to 24.2% (16/70) of treated cases. Subgroup analysis revealed cords, single files, and neuroendocrine-like morphologies are present in higher frequency in neoadjuvant treatment-resistant cases and associated with poorer prognosis. Conclusion: In this study, we have identified new morphological pat- terns of EAC associated with poor prognosis. This is a first of a kind study focused on identifying new prognostically significant morpholog- ical patterns of EAC. We are currently exploring clinical correlations and molecular underpinnings of these different morphological patterns. In addition, we are developing a deep learning pipeline to aid in mor- phological identification. Our overall goal is to develop a clinically relevant classification system that identifies therapeutic vulnerabilities. PS-17-028 Analysis of tertiary lymphoid structures (TLSs) in microsatellite stable colorectal cancer (MSS-CRC) B. Palomar De Lucas*, M. García, N. Tarazona, J. González, M. Huerta, D. Moro, A. Cervantes, C. Martinez-Ciarpaglini *Incliva, Biomedical Research Institute, Hospital Clínico Universitario de Valencia, Spain Background & objectives: TLSs have been demonstrated as a promo- tor of efficacious immune response in solid tumours. We aim to explore the content of TLSs in a series of MSS-CRC and its relationship with the consensus molecular subtype (CMS) and the microenvironment composition. Methods: We retrospectively evaluated a series of 102 surgically resected colorectal cancer cases. The TLSs content and type were evaluated on HE whole tissue sections. A 96 custom gene panel for nCounter assay was used to classify colon cancer into CMS subtypes. Whole tissue sections were immunostained and scanned for CD3, CD4, CD8, CD163, FOXP3 and PD-L1 evaluation. Results: We found the CMS4 to have a lower content of TLSs com- pared to the CMS2/3 subtypes (p=0.042). Tumours showing secondary follicles were associated with low tumour budding grade (p=0.015) and were more frequent in the right colon (p=0.050). The presence of TLSs was associated with a higher concentration of CD3, CD4 and CD8 cells in the tumour front (p=0.031, 0.013, 0.049 respectively) and decreased levels of CD163 positive macrophages (p=0.045). FOXP3 and PD-L1 expressions were not significantly correlated to TLSs content. Conclusion: Our study suggests that TLSs may potentially help to recognize a subset of MSS-CRC associated with active antitumoral immune response and less aggressive features Funding: Project PI21/00695 financed by ISCIII and co-financed by FEDER funds PS-17-029 Features of PDX-1 expression in gastric neuroendocrine tumours, neuroendocrine carcinomas and carcinomas V. Pechnikova*, L. Mikhaleva, L. Gurevich, O. Vasyukova, A. Birukov, K. Midiber, R. Vandysheva, N. Shakhpazyan, Z. Gioeva, A. Konyu- kova, L. Kakturskiy *Avtsyn Research Institute of Human Morphology of Federal State Budgetary Scientific Institution "Petrovsky National Research Centre of Surgery", Russia Background & objectives: The research aimed at studying the PDX-1 expression features in gastric neuroendocrine tumours (NETs), neu- roendocrine carcinomas (NECs) and gastric carcinomas (GC). Methods: The study included 78 patients with 89 solitary and multiple NETs G1-G3, NECs. Comparison group included 31 GCs including 13 signet-ring cell carcinomas. We used PDX-1 (1:100, EP139) and Ki-67 antibodies. Positive PDX-1 reaction showed nuclear staining in most