ECP 2023 Abstracts

S44 Virchows Archiv (2023) 483 (Suppl 1):S1–S391 13 to better guide neurosurgeons on the choice of the most appropriate surgical approach. OFP-11-007 Neuroanatomical location of common brain metastases by primary site with assessment of provided history M. Bonert*, A. Berzins, H. Begum, J. Lu, A. Swaminath, A. Naqvi *McMaster University / St. Joseph’s Healthcare Hamilton, Canada Background & objectives: Brain metastases are a frequent occurrence in neuropathology practices and are known to favour certain neuro- anatomical locations based on their primary site. This work examines metastases through the lens of pathologic specimens only and the pri- mary site per pathology report. Methods: All brain pathology cases accessioned 2011-2020 were retrieved from a regional centre. Specimens were classified by neuro- anatomical location (frontal /temporal/ occipital/ parietal/ cerebellum/ other), diagnosis, diagnostic category and clinical history in relation to the final diagnosis with a hierarchical free text string-matching algo- rithm (HFTSMA) and pathologist review. Randomly selected cases were reviewed to assess the HFTSMA. Results: The cohort had 4,625 cases. 843/4,625 were metastases per HFTSMA; 96% were correctly classified as per 200/4,625 randomly selected cases. 493 were classified as metastases with a single defined primary site on report review from 472 patients. Primaries from breast (38%), gynaecologic tract (35%), and gastrointestinal tract not otherwise specified (33%) most frequently spread to the cerebellum. Kidney metastases (35%) were most frequently found in the occipital lobe. Lung (35%), metastatic melanoma (44%) and colorectal primaries (29%) were mostly commonly found in the frontal lobe. The provided clinical history predicted the primary in 198 patients (42%), was discordant in 16 patients (3%) and non- contributory in 258 patients (55%). Conclusion: The hierarchical free text string-matching algorithm assisted categorization facilitated the analysis; however, it was not sufficiently accurate without pathologist review. In the majority of brain metastases, the provided clinical history was non-con- tributory; this suggests surgeon-neuropathologist communication may have the potential for optimization. The distribution of the metastatic tumours in the brain is dependent on the primary cancer. OFP-11-008 Characterization of the protein expression of the promising immu- notherapy targets VISTA, LAG-3 and PRAME in a cohort of southern French patients with primary uveal melanoma N. Lamas*, S. Lassalle, A. Martel, S. Nahon-Estève, A. Macocco, K. Zahaf, S. Lalvee, J. Fayada, V. Lespinet-Fabre, O. Bordone, F. Pedeu- tour, S. Baillif, P. Hofman *Life and Health Sciences Research Institute (ICVS), School of Medi- cine, University of Minho, Campus de Gualtar, Braga, Portugal; Ana- tomic Pathology Service, Pathology Department, Centro Hospitalar Universitário de Santo António (CHUdSA), Porto, Portugal Background & objectives: Novel cancer therapies based on immu- notherapy have changed the treatment landscape and overall survival prospects for patients. VISTA, LAG-3 and PRAME are emerging tar- gets of immunotherapy for different solid tumours, but their relevance in primary uveal melanoma (pUM) is unknown. Methods: Using immunohistochemistry in representative whole sections of pUM cases of a cohort of 30 patients from one sin- gle centre (Nice University Hospital, Nice, France), we studied and characterized the protein expression of VISTA, LAG-3 and PRAME. The expression of each of these markers was correlated with different clinical and pathological parameters, including metastases onset and overall survival. Results: VISTA and LAG-3 protein expression was identified in small lymphocytes infiltrating the pUM cases, while no expression of both proteins was detected in uveal melanoma cells. Contrarily, PRAME nuclear expression was identified in uveal melanoma cells, while no expression in the tumour infiltrating immune cells was observed. Increased levels of VISTA expression in tumour infiltrating lympho- cytes (TILs) were associated with BAP1 nuclear preservation and a better prognosis for patients. Higher levels of LAG-3 in TILs were associated with higher levels of CD8-positive TILs. PRAME nuclear positivity in uveal melanoma cells was associated with epithelioid cell uveal melanoma histologic subtype, higher mitotic numbers and a higher percentage of chromosome 8q gain. Conclusion: Our study demonstrates that VISTA is a novel relevant immune checkpoint molecule in pUM. In addition, we further confirm that LAG-3 and PRAME are potentially important immunotherapy tar- gets in the treatment of uveal melanoma patients. Together, our results help to expand the range of immunotherapy candidate molecules that are relevant to modulate in uveal melanoma, which currently has a dismal prognosis once metastases develop, since therapeutic options for the metastatic disease are mostly ineffective. OFP-11-009 Prognostic significance of BAP1 protein expression in uveal mela- noma in comparison to The American Joint Committee on Cancer (AJCC) staging and The Cancer Genome Atlas (TCGA) system S. Owens*, C. Hegarty, N. Walsh, N. Horgan, V. O’Neill, J. O’Neill, L. Ivers, S. Kennedy *Research Foundation, Royal Victoria Eye and Ear Hospital, Dublin, National Ophthalmic Pathology Laboratory, Royal Victoria Eye and Ear Hospital, Dublin, School of Biotechnology, Dublin City Univer- sity, Ireland Background & objectives: Uveal Melanoma (UM) is a rare and aggres- sive malignancy that metastasises in approximately 50% of cases. This study aimed to evaluate the role of nuclear BAP1 (nBAP1) expression in overall survival of UM compared to AJCC staging and TCGA system. Methods: A detailed review of pathology files, cancer registry files and death certs were accessioned and tabulated for UM patients who received enucleation between 1974 and 2022. BAP1 immunohistochemistry (IHC) results were obtained from stained BAP1 IHC slides or UM tissue microarrays. nBAP1 expression was correlated with metastasis free survival to compare the prognostic value of AJCC staging and TCGA system. Results: 308 UM patients aged 11-96 [median age: 63] were ana- lysed by IHC for nBAP1 expression. Loss of nBAP1 protein expres- sion was detected in 144/308 (47%) of patients. 124/308 (40%) devel- oped metastasis, 71/124 (57%) were nBAP1 negative. Clinical, pathological, and genomic characteristics were correlated to identify the best prognostic indicators for overall survival (OS). Through multivariate analysis (95% confidence interval) of clinicopathological features with OS, nBAP1 negative expression [P=0.030] was shown to be an independent factor along with older age and presence of metastasis whereas AJCC and TCGA fell out of significance. When correlated with clinicopathological features, loss of nBAP1 expression was significantly [Log rank, P=0.0008] associated with poor survival. Conclusion: In this study, nBAP1 protein expression proved to be a more reliable prognostic indicator for overall survival than AJCC staging or TCGA classification. This study also provides support for accurate prognostication of UM patients in routine histology laboratories by means of immunohis- tochemistry for BAP1 alone, without the need to refer all cases for genetic studies, when this is not readily available. It provides further evidence that BAP1 protein expression is a more powerful prognostica- tor for overall survival than chromosomal studies.