ECP 2023 Abstracts

S112 Virchows Archiv (2023) 483 (Suppl 1):S1–S391 13 Methods: The prognostic and agnostic biomarkers were evaluated in 3546 CRC cases (324 non-metastatic(M0) and 3222 metastatic(M1), included in the MSK-MetTropism dataset in the "cBioportal"). 1684 cases were evalu- ated in two groups as right and left colon, and in three groups as right, left, and rectum as well as the anatomical sub-region distribution of biomarkers. Results: In microsatellite stable (MSS) CRC cases, ARID1A genomic alterations (p<0.001) in non-metastatic cases, KRAS genomic altera- tions (p=0.043), and TP53 mutations (p=0.038) in metastatic cases were more common. In cases of MSS metastatic CRC, tumour muta- tional burden(TMB) <10/Mb (p=0.023), copy number alterations (CNAs) (p<0.001) ), CDKN2A genomic alterations (p<0.001) and MET amplifications (p=0.047) had a shorter overall survival. Targ- etable fusions were more common in the right colon and MSI, TMB- high, KRAS, and BRAF-wild-type cases. PIK3CA genomic alterations, MSI, and TMB≥10 decreased in the rectosigmoid region, while KRAS genomic alterations increased. The rectum differs from the left colon by higher frequency of KRAS genomic alterations and total amplification and less BRAF genomic alterations. Conclusion: Our analysis is informative regarding the distribution and prognosis of fusions, CNAs, and other genomic changes in agnostic bio- markers. CNAs, CDKN2A genomic alterations, and MET amplifications have a poor prognosis, while MSS-TMB≥10/Mb cases have a better prog- nosis, like MSI-TMB≥10/Mb cases. Our findings are remarkable because of the possible importance of ARID1A and CDKN2A in the right colon and some differences in the left colon regarding other agnostic biomark- ers, especially amplifications of the rectosigmoid region and rectum. PS-17-034 Revisiting early gastric cancer in search of a rare entity: “gastric adenocarcinoma of fundic-gland type” S.N. Sayir*, H.K. Kahraman, A.R. Akur, H. Berber, S. Yüksel, B. Savaş, A. Ensari *Ankara University, Faculty of Medicine, Turkey Background & objectives: Gastric adenocarcinoma of fundic-gland type(GA-FG) is a recently defined subtype mostly presenting with early stage and good prognosis. Its biological behaviour as early gas- tric cancer(EGC) encouraged us to re-examine our EGC cohort with a fresh look in search of GA-FG. Methods: A total of 100 EGC cases were re-evaluated for gastric cancer subtypes, grade, depth of invasion, lymphovascular invasion(LVI), type of specimen, background mucosa. Presence of GA-FG pattern which is characterized by anastomosing glands lined by cells of oxyntic mucosa in the deeper parts covered with normal foveolar surface was noted. Statisti- cal analysis was performed using Chi-Square and Mann-Whitney tests. Results: Patient age ranged between 37-93 years and 66% were male. GA-FG pattern was detected in 35 cases 8 of which were purely GA-FG type. Majority(38) showed tubular type, followed by 12 poorly cohe- sive, 5 mixed, 4 papillary, 2 signet ring, 1 mucinous and 1 MiNEN. Submucosal(42%), lamina propria/muscularis mucosa invasion(36%) and insitu(22%) presentation were observed in the cohort. GA-FG cases were significantly(p=0.012) older(77.63) than other subtypes (68.27) and most(71.4%) presented with earlier stages (Tis/T1a) compared to others (p=0.039). Lymph node metastasis was significantly(p=0.035) more frequent in GA-FG(20%) compared to other group(6.2%). There was no difference between the groups for grade, LVI, dysplasia in background mucosa which was mostly atrophic with intestinal metaplasia(79%). Conclusion: In accordance with the recent literature our results revealed that GA-FG type is associated with lower stages, therefore should be considered within the spectrum of EGC. Reviewing EGC cases would provide new insights regarding morphological features of GA-FG pre- senting either in pure form or as an accompanying pattern. This approach would justify endoscopic treatment as more appropriate for such patients rather than surgery. Thus, it is of paramount importance to recognize and rightfully diagnose GA-FG cases despite its relative rarity. PS-17-035 STING: the key in dMMR colo-rectal cancer in the era of immunotherapy? G. Scellier*, M. Bubenheim, N. Piton, F. Di Fiore, J. Sabourin *CHU Rouen, Department of Pathology, France Background & objectives: 30% of deficient mismatch repair (dMMR) colorectal cancer (CRC) are primary resistant to immunotherapy (ICI). We hypothesized that STING expression could be predictive of ICI response in CRC. We aimed to compare STING expression between pMMR and dMMRCRC. Methods: A single-centre historical cohort of CRC surgically resected between 2017 and 2021 was constituted. MMR status was assessed by both immunohistochemistry (IHC) and PCR. dMMR CRC were matched with proficient MMR CRC according to UICC 2017 stage and date of receipt of the specimen. STING IHC (D2P2F clone, Cell Signaling®) was blindly evaluated with determination of H-score on tumour cells. Results: The cohort consisted of 96 patients with CRC (48 dMMR and 48 pMMR). STING median Hscores were 80 (Q1-Q3: 10-150) for dMMR CRC, and 10 (Q1-Q3: 0-40) for pMMR CRC (p < 0.001). In our cohort, two patients with dMMR CRC were treated by immuno- therapy : the first had a clinical complete response at 2 years (initially STING H-score at 80) and the second had a partial response at 1 year (initially STING H-score at 160). We also identified a subgroup of pMMR CRC with high STING expres- sion (H-score ≥ 80, n=10/48), which share morphological features. In this subgroup, we did not identify any POLE mutation by targeted PCR (SNaPshot™). Conclusion: Overall, STING was overexpressed in dMMR CRC com- pared to pMMR CRC. However, 25% of dMMR CRC patients had a weak or null expression of STING and could represent nonresponders to ICI. Our results support our hypothesis of a major role of STING in the immune response of dMMR CRC. STING immunostaining could be a good predictive biomarker of ICI response in dMMR CRC. Clini- cal validation is ongoing. PS-17-036 Comparative analysis of Granzyme B expression in refractory coeliac disease type II, untreated coeliac disease and normal duodenal mucosa D. Skrobo*, S. Bennett, F. Murray, A. O’Donoghue, A. Hayat, V. Byrnes, C. Brodie *Galway University Hospital, Ireland Background & objectives: Refractory coeliac disease type II (RCDII) does not respond to a gluten-free diet. GranzymeB (GrB) is a protease known for its pro-apoptotic function. Its role in RCDII pathogenesis is unclear. We compared the GrB immunohistochem- istry in 3 cohorts. Methods: This retrospective study consisted of 3 cohorts. RCDII, untreated coeliac disease (CD) and a normal control group. N=26 patients, with 8 patients in each group. GrB expression was evaluated using immu- nohistochemistry (IHC) on duodenal biopsies. Morphology was evaluated on H&E and the number of positive GrB cells in the lamina propria (LP) and intraepithelial lymphocytes (IEL) were counted per/mm2. Results: The RCD cohort bore 4-42 GrB positive IEL’s/mm2 with a median of 19 per/mm2, mean 21. In the LP there were 9-101 GrB positive cells/mm2 with a median of 62, mean 60. The CD cohort bore 1-41 GrB positive IEL’s/mm2 with a median of 7per/mm2, mean 14. In the LP there were 11-270 GrB positive cells/mm2 with a median of 51, mean 80. In the normal cohort there were 0-2 GrB positive IEL’s/ mm2 with a median of 0 per/mm2, mean 0.5. The staining pattern in RCDII and CD cohort was a dot-like cytoplasmic pattern. The staining pattern in NDM was fine-granular cytoplasmic pattern. Conclusion: In this small hypothesis testing study we noted that there was a different staining pattern in the intraepithelial and lamina propria