ECP 2023 Abstracts

S4 Virchows Archiv (2023) 483 (Suppl 1):S1–S391 13 OFP-01-010 Specific morphological characteristics predict microsatellite insta- bility status in gastric cancer J. Almeida*, J.R. Silva, L. Mascarenhas-Lemos, C. Neto do Nasci- mento, D. Sousa Marques, X. Wen, L. Pinho, R. Maio, P. Pontes, L. Cirnes, M. Cravo, F. Carneiro, I. Gullo *Department of Pathology, Centro Hospitalar Universitário de São João (CHUSJ), Porto, Portugal Background & objectives: The evaluation of microsatellite instabil- ity (MSI) status in gastric cancer (GC) is pivotal for the definition of prognosis and optimal treatment approach. In this study, we aimed at identifying morphological features that might be associated to MSI- high status in GC. Methods: The series encompassed 140 GCs. Tumour morphology was evaluated in endoscopic biopsies (EB) and surgical specimens (SS) according to Laurén and WHO classification. Specific morphologi- cal features were evaluated, including tumour grade, presence of solid component, extracellular mucin pools, areas with prominent lymphop- lasmacytic and/or neutrophilic inflammatory infiltrate (distant from ulceration/perforation). MSI status was evaluated by multiplex-PCR and immunohistochemistry for mismatch-repair proteins. Results: The series encompassed 38 MSI-high GC (27,1%). MSI-high GCs occurred more frequently in older (median age=73 years, p<0.01) females (57.9%, p=0.012) and in the distal third of the stomach (89.5%, p=0.037), when compared with microsatellite stable (MSS) tumours. No statistically significant association was found between MSI-high status and Laurén or WHO classifications. The evaluation of specific morphologic characteristics in SS revealed that MSI-high GC showed more frequently solid and/or mucinous components (p=0.034 and p<0.001, respectively), as well as the presence of “neutrophil-rich stroma” (p<0.001). Both solid areas and extracellular mucin lakes were discriminating features for the identification of MSI-high cases also in EB (p=0.002 and p=0.045, respectively). Conclusion: GC is a highly heterogenous tumour and few studies have assessed possible morpho-molecular correlations. Despite the morpho- logical heterogeneity of GC harbouring MSI-high status, we identified specific histopathological features that should prompt the search for this molecular subtype both in EB and SS, namely solid component and extracellular mucin lakes. To our knowledge, this is the first study describing a neutrophilic-rich inflammatory infiltrate in MSI-high GC, a feature which predicted MSI-high status in up to 85% of GC cases. This research was partially co-financed by Hospital da Luz under the initiative “Luz Investigação” in the context of the Group GENIUS (Reference LH.INV.F2019015). Part of IdyllaTM reagents have been provided free of charge by Biocartis. The funding source did not have any influence on the design, conduction, analysis and interpretation of data and report of the results for this study. OFP-01-011 The complexity of shapes; how the circularity of tumour nodules impacts prognosis in colorectal cancer N. Brouwer*, A. Khan, J. Bokhorst, F. Ayatollahi, J. Hay, F. Doubrava- Simmer, N. Hugen, H. de Wilt, I. Zlobec, J. Edwards, I.D. Nagtegaal *Radboud University Medical Center, The Netherlands Background & objectives: The current definition of tumour deposits (TDs) in colorectal cancer (CRC) staging is subjective and leads to high interobserver variability. In this study, objective assessment of the shape of lymph node metastases (LNMs) and TDs was correlated with outcome. Methods: 190 cases of stage III CRC from IGMP (Bern) were included in the test cohort. Slides with LNMs and TDs were roughly annotated and processed using a segmentation algorithm to determine their shape. The complexity ratio was calculated for every shape and correlated with outcome. A cohort of 169 stage III CRC cases from QEUH (Glas- gow) was used as validation. Results: A significantly higher disease-free survival (DFS) for N1 than N2 cases was observed in both cohorts, as to be expected. TDs showed a significantly more complex shape than LNMs with extranodal extension (ENE), which were again more complex than LNMs with- out ENE (p<0.001). In the test cohort, patients with the highest sum of complexity ratios had a significantly lower DFS (p<0.01), which remained when only the nodule with the highest complexity was taken into account (p<0.001). This maximum complexity ratio per patient was identified as an independent prognostic factor in the multivariate analysis (HR 3.12, p<0.05). The validation cohort confirmed these results. Conclusion: More complex nodules in stage III CRC were corre- lated with a significantly worse DFS, even if only the most complex nodule was taken into account. These results suggest that more complex nodules are a reflection of a more aggressive tumour biol- ogy. Since most of the more complex nodules were diagnosed as TDs, we suggest to provide a more prominent role for TDs in the nodal stage and possibly include an objective complexity measure in their definition. OFP-01-012 Tumour deposits - a heterogeneous group of lesions with different metastatic potential A.S. Oguz Erdogan*, N. Brouwer, V. Angerilli, T. Haddad, S. Lent- vanVliet, N. Rutgers, F. Doubrava-Simmer, I.D. Nagtegaal *Radboud University Medical Center, The Netherlands Background & objectives: Tumour deposits (TDs) are tumour aggre- gates in the mesocolon. Several possible pathways including lympho- vascular invasion, lymph nodes and perineural invasion have been sug- gested. This study aims to identify the TDs by evaluating them in terms of well-known metastatic pathways. Methods: We examined histopathological specimens from 646 colo- rectal cancer patients and identified 136 patients with 329 tumour deposits (TDs). We conducted serial sectioning and staining of TDs using HE, EVG, CD34, D2-40 and S100. Results: Based on the presence or absence of haematovascular inva- sion, lymphovascular invasion, lymph node involvement, and perineu- ral invasion we classified TDs into three groups: those with a single metastatic origin (171, 52%), those with multiple metastatic origins (115, 35%), and an unknown group (43, 13%) where no metastatic pathway was evident. Haematovascular pathway is the most common route for TDs. Conclusion: Our findings illustrate that, TDs are a highly heterogene- ous group of lesions and the haematovascular pathway plays a signifi- cant role in TDs formation. Funding: KWF OFP-01-013 Stroma AReactive Invasion Front Area (SARIFA) as novel prog- nostic biomarker in colorectal cancer is characterized by a distinct transcriptional signature associated with stromal cell infiltration and lipid metabolism N.G. Reitsam*, V. Grozdanov, B. Grosser, C.M.L. Löffler, H.S. Muti, J.N. Kather, B. Märkl *Pathology, Medical Faculty, University of Augsburg, Germany Background & objectives: Recently, we established Stroma AReac- tive Invasion Front Areas (SARIFA), defined as direct contact between tumour cells and adipocytes, as novel hematoxylin-and-eosin (H&E) based prognostic biomarker in gastrointestinal cancers. We now com- prehensively evaluated gene expression signatures with regards to SARIFA-status.