ECP 2023 Abstracts

S113 Virchows Archiv (2023) 483 (Suppl 1):S1–S391 13 lymphocyte population between RCD, untreated CD and the normal patient cohorts. A trend was observed in the RCD cohort with more GrB positive IEL’s and fewer GrB positive cells in the LP. PS-17-037 A closer look at the implications of CD68 in gastrointestinal stromal tumour behaviour I.A. Spiridon*, A.D. Timofte, I.D. Căruntu *"Grigore T. Popa" University of Medicine and Pharmacy Iasi, Romania; Institute of Image Guided Surgery IHU-Strasbourg, France Background & objectives: Macrophages are integral part of the immune response, with primary phagocytosis function. Upregulation of these CD68+ cells is observed in various cancers, with impact on prognosis. Our study focuses on the involvement of intratumoral mac- rophages in gastrointestinal stromal tumour(GIST) behaviour. Methods: CD68 immunohistochemical (IHC) evaluation was carried out on 44 cases of small bowel GISTs from adult patients, diagnosed based on histology and the classical panel of markers (CD117, CD34, DOG1). We analysed the spatial distribution of positive cells on WSI of GIST and correlated tissue expression with the clinicopathological factors, while also assessing the impact on survival and disease-free interval. Results: Quantitative IHC expression of CD68 using automated cell counting software QuPath rendered a more precise evaluation of the number of positive cells/mm2 and revealed marked intratu- moral heterogeneity. The distribution in tumour core versus tumour periphery was varied, with immunoreactive cells mostly observed as present in isolated or small groups (<10 cells), some with vaso- centric aggregation. Intertumoural heterogeneity revealed marked differences, which correlated with mitotic activity and the presence of myxoid degeneration of the stroma (p<0.05). Significant corre- lations with other clinicopathological factors were not confirmed. However, CD68 expression was correlated with patient survival and disease-free interval (p<0.05), as estimated by the Kaplan-Meier method and log-rank test. Conclusion: Our results show that CD68 positive cells display complex intratumoral spatial distribution that correlates with changes in stroma, indicating intricate interactions with the tumour microenvironment. In this context, we have demonstrated that the CD68 expression profile is also impactful on patient survival. These results can be further capital- ized by including this marker into immunoscores aimed at characterizing tumour-associated response in GISTs and refining the currently existing systems used in estimating patient prognosis and survival. This work was supported by French state funds managed within the “Plan Investissements d’Avenir” and by the ANR (reference ANR-10-IAHU-02). PS-17-038 Analytical and clinical performance of the VENTANA CLDN18 (43-14A) RxDx Assay in gastric and gastroesophageal junction adenocarcinoma tissue samples for patient identification in two phase 3 trials of zolbetuximab S. Stratton*, L. Pang, J. Pugh, M. Kouzova, D. Baldwin, J. McDonald, J. Buckmeier, A. Guerrero, D. Moran *Roche Diagnostics Solutions, USA Background & objectives: Immunohistochemical detection of tight junction protein Claudin-18 (CLDN18) using the investigational VEN- TANA CLDN18 (43-14A) RxDx Assay was performed in pivotal tri- als to help identify patients with gastric or gastroesophageal junction (G/GEJ) adenocarcinoma who may benefit from zolbetuximab, a CLDN18.2-targeted therapy. Methods: The VENTANA CLDN18 (43-14A) RxDx Assay was designed for high sensitivity/specificity and underwent rigorous inter- laboratory, instrument, day, run, and reader precision testing using formalin-fixed, paraffin-embedded, tumour specimens. A clinical cut- off of ≥75% of tumour cells with moderate-to-strong membranous CLDN18 staining was defined as CLDN18.2-positive. Over 4000 sam- ples were analysed from the recent phase 3 SPOTLIGHT and GLOW trials of zolbetuximab. Results: Analytical performance studies indicated within- and between- reader precision of 98.7% Overall Percent Agreement (OPA) across three readers. Between-day and within-run studies showed 100% agreement. Inter-laboratory reproducibility (3 sites) exceeded 90% in all categories, with inter-site OPA of 91.1%, inter-reader OPA of 94.8%, and overall OPA of 95.0%. Initial (first-pass) and final acceptability rates for overall staining were 94.9% and 98.7%, respectively in SPOTLIGHT. Patients with HER2-negative, locally advanced unresectable or metastatic G/GEJ adenocarcinomas, enrolled in SPOTLIGHT (NCT03504397) or GLOW (NCT03653507), with CLDN18.2-positive tumours had statistically sig- nificant prolonged progression-free survival (PFS) and overall survival (OS) when treated with zolbetuximab + chemotherapy versus placebo + chemotherapy, demonstrating clinical performance. Conclusion: The VENTANA CLDN18 (43-14A) RxDx Assay met all analytical criteria for performance, demonstrating precision scoring of CLDN18 status in G/GEJ adenocarcinomas. The clinically significant improvements in PFS and OS in CLDN18.2-positive patients, identified by the VENTANA CLDN18 (43-14A) RxDx Assay, support the clinical utility of this assay as a companion diagnostic for reliably identifying patients who may benefit from first-line treatment with the CLDN18.2- targeted therapy zolbetuximab in combination with chemotherapy. This study was funded by Astellas Pharma, Inc., which is the legal entity responsible for governance, coordination, and running of the study. Medical writing support was provided by George Pellegrino, MD, PhD, of Oxford PharmaGenesis Inc., Newtown, PA, USA, and was funded by Astellas Pharma, Inc. PS-17-039 Insulinoma-associated protein 1 expression in primary neuroen- docrine neoplasms of the gastrointestinal and pancreaticobiliary tracts: a study from a tertiary care hospital of Coastal India P. Suresh*, E. Edwin, S. Rao, S. Sreeram, H. Kini, J. Kini, S. Basavaiah, V. B *Kasturba Medical College Mangalore, Manipal Academy of Higher education, Manipal, India Background & objectives: Neuroendocrine neoplasms (NENs) are uncommon tumours that can arise from the gastroenteropancreatic(GEP) system. Insulinoma-Associated Protein 1(INSM1) is a novel marker found in developing neuroendocrine tissues and tumours. We aimed to evaluate INSM1 expression in primary GEP-NENs. Methods: Retrospective review (2016-2021) was used to assess clini- cal features and histomorphology of 70 cases of GEP-NENs. Paraffin- embedded tissue was available in 49 GEP-NENs which along with 10 other non-neuroendocrine gastrointestinal neoplasm controls were subsequently stained with INSM1, Syn, CgA and Ki-67. Results: The patients ranged from 13-87 years of age with the majority of them over 50 years (68.5%) and most men (62.8%). The most com- mon site for GEP-NENs was the duodenum (34.3%), followed by the rectum (20%). INSM1, CgA, and Syn expression were noted in 71.4%, 57.1%, and 87.8% of GEP-NENs respectively. INSM1 was more sensi- tive than CgA but less sensitive than Syn and as specific as CgA and SYN (Sensitivity – 71.4%, 57.1%, and 87.8% and specificity – 90%, 90%, and 90% of INSM1, CgA, and Syn respectively) Conclusion: INSM1 is a promising novel marker for GEP-NENs. Compared to traditional neuroendocrine markers, INSM1 is more sensitive and as specific. In addition, we found that INSM1 showed positivity in G3 NETs as compared to CgA and Syn. Further studies on INSM1 in NENs of the entire body are recommended to validate INSM1 as a single neuroendocrine diagnostic marker.