ECP 2022 Abstract Book

Virchows Archiv (2022) 481 (Suppl 1):S1–S364 13 Results: To circumvent morphologic cell variability, HALO AI was used to create a Nuclei Segmentation network that per- formed well across all cancer types analysed. Rather than relying on PanCK and E-cadherin biomarkers to identify tumour cells, a HALO AI Nuclear Phenotyper algorithm was trained to recog- nize tumour cells from stromal cells independently of biomarker expression and staining variability. The Nuclear Phenotyper and Nuclear Segmentation networks were embedded into the Highplex FL module of HALO for analysis of tumoral proliferation, using pHH3 and Ki67 biomarkers. The Spatial Analysis module of HALO was used to examine the proximity of cytotoxic T lymphocytes and macrophages and their level of infiltration of the tumour margin. Conclusion: HALO and HALO AI software provide easily adapt- able tools for the analysis of the TME in any tissue type and with any set of markers. It can be applied to IMC images in order to standardise cell segmentation, tissue segmentation, cell phenotyp- ing and spatial analysis. PS-15-030 Genomic landscape analysis of ERBB3-mutated human can- cers reveals common co-occurrence with activating ERBB2 alterations I. Odintsov*, R. Somwar, M. Ladanyi *Brigham and Women’s Hospital, USA Background & objectives: ERBB3 is a member of the ERBB recep- tor tyrosine kinase (RTK) family, which includes EGFR, ERBB2 and ERBB4. In this study we describe the prevalence of activating ERBB3 mutations across human cancers and analyse the genomic landscape of ERBB3-mutated tumours. Methods: Retrospective review of MSK-IMPACT (DNA-based NGS) data (January 2014-June 2021) was performed (n=72000 pts). ERBB3 mutations were annotated as hotspot and/or activat- ing using OncoKB database and current literature. Data analysis, visualization and statistical analysis were performed using R Studio and GraphPad PRISM. Results: Out of 72000 patients tested, 582 patients (1%) harboured an activating ERBB3 alteration. The majority of tumours with ERBB mutations were colorectal, gastric and oesophageal cancers, small bowel carcinomas, bladder urothelial carcinomas, uterine endometrioid carcinomas, and breast cancers. Most mutations in ERBB3 occurred in the extracellular domain (85%) with only 15% found in the kinase domain, consistent with the allosteric activator function of this receptor. Concurrent alterations in ERBB2 were found in 19% of ERBB3-altered tumours and were present across the above tumour types. Of note, no such association was observed for EGFR. Conclusion: ERBB3 mutations are potential driver alterations with no FDA-approved therapy. A significant proportion of activating ERBB3 mutations co-occur with activating ERBB2 alterations sug- gesting synergistic tumourigenic effects. Our work highlights the importance of broad genomic testing to detect ERBB3 mutations, as these may identify patients potentially responsive to ERBB2 inhibition or antibody-mediated targeting of ERBB3. PS-15-031 Mir-9 and their putative targets expression in prostate cancer I. Benedetti*, L. Barrios, J. Rebollo *Universidad de Cartagena, Colombia Background & objectives: There are divergent descriptions of the role of mir-9 in terms of its support or suppression of tumour development and metastasis in different tumours. It has been found overexpressed in prostate cancer (PCa) tissue compared to benign prostate tissue (BPT). Methods: In a prostate tissue microarray with 145 BPT and 149 PCa cores, from prostatectomy samples of patients with localized PCa, using miRNAscope® 2.5LSRedISH, miR-9-5p expression was scored and compared between both conditions. Possible mir-9 targets were sought in miRTarBase, their expression was explored in the tumour tissues of the Cancer Genome Atlas (TCGA) through bioinformatics tools of GEPIA2 web server. Results: MiR-9 was overexpressed in PCa compared to BPT. In the miRTarBase, 526 mir-9 target genes validated with at least one experimental assay were identified, and 24 genes with the strongest evidence of interaction with miR-9 were selected. The higher expression level in PCa was for CDH1, RAB34, AP3B1, CCNG1, SRF, TGFB1, ID2, FOXO3 y CCND1. When compared with BPT, the expression of 3 genes (BCL6, RAB34 and NTRK3) was downregulated in PCa, while CDH1 was overexpressed in the prostate cancer tissues (P < 0.001). Moreover, miR-9 gene targets CDH1, BCL6, CCND1 and PRDM1 showed truncating mutations, amplifications, deep deletion and splice mutations in some of the cancer datasets. Conclusion: The analysis of the mir-9 and their target genes expression in normal versus cancer prostate tissues suggest that this miRNA may be regulating tumour initiation, progression, and metastasis processes through the downregulation of the Neurotrophic Receptor Tyrosine Kinase 3 (NTRK3), which has been found altered in breast carcinomas and other cancers, or the downregulation of Cadherin 1 (CDH1), whose loss of function is thought to contribute to cancer progression by increasing proliferation, invasion, and metastasis. Funding: Universidad de Cartagena, Cartagena, Colombia PS-16 | Poster Session Pulmonary Pathology PS-16-001 Clinicopathological features of primary pulmonary Hodgkin lymphoma: a multicentre study and literature review of 110 cases H. Jung*, T. Lee *CHA Ilsan Medical Center, Republic of Korea Background & objectives: Primary pulmonary Hodgkin lymphoma (PPHL) is extremely rare compared to secondary lung involvement by Hodgkin lymphoma. And overall clinicopathological characteristics has been unclear because of its low prevalence. Methods: We proceeded the multicentre retrospective study of ten cases histologically confirmed as PPHL from 1995 to 2019. With analysing clinicopathological features of these 10 cases, additional literature review of 100 cases was conducted together. We analysed the total 110 cases of PPHL about sex/age distribution, radiologic findings, histologic subtype and treatment. Results: Female to male ratio was 6:4 and mean age was 41 years old. Although three patients had no symptom, seven had several localized and general symptoms including cough, sputum, chest discomfort/ pain and weight loss. With chemotherapy, five had complete remis- sion and three had partial response. Some cases had not been diag- nosed as PPHL in initial needle biopsy, so that three patients underwent surgical resection. Differential diagnosis of PPHL included epithelial malignancy, such as adenocarcinoma, inflammatory diseases like tuber- culosis, inflammatory myofibroblastic tumour, IgG4 related lung dis- ease and other hematologic malignancy. With literature review, female predominance and a single peak at younger age were identified. Radio- logical findings were variable often with cavitation. S149