ECP 2022 Abstract Book

Virchows Archiv (2022) 481 (Suppl 1):S1–S364 13 tumour growth in animal model of glioblastoma through unclear mechanism. Methods: We use immunohistochemistry and in situ hybridization to identify location and cell of origin for LAMB1/2 production in human brain. Results: In quiescent state brain the microvasculature but does not express LAMB1, but expresses LAMB2 at the sites of blood brain and CSF brain barrier. Remodelling of microvasculature in suba- cute stroke involves initial deposition of LAMB1 by proliferating endothelium, followed by an encasement by LAMB2. Low grade diffuse astrocytomas show no LAMB1 expression. Microvascular hyperplasia in GBM show striking deposition of LAMB1, while LAMB2 coverage trails behind. Bevacizumab induces a loss of LAMB1 and normalizes LAMB2 coverage. Conclusion: Distribution of LAMB2 correlates with sites controlling fluid permeability. Expression of LAMB1 corresponds to endothelial cells and coincides with angiogenesis. Expression of LAMB2 lags behind LAMB1 and its deficiency in the microvascular wall correlates with increased permeability. OFP-13-010 Molecular genetics and immunostaining of relapsing inoperable meningiomas located at the base of skull (BS) or in frontal areas, before radiotherapy M. Alshemeili*, M. Barritault, D. Poncet, E. Jouanneau, D. Meyronet *Hospice Civil de Lyon, France Background & objectives: Our experience in screening for targ- etable molecular alterations of untreatable meningiomas led us to hypothesise that these mutations were less frequent than expected considering available studies. Our goal to provide prospective clinic-pathological/ molecular data to support future pharmacological targeted therapies. Methods: From 2018 to 2022, the molecular status of p-AKT and SHH activating molecular alterations was prospectively determined using NGS in the first biopsy of all relapsing patients after surgery with pathologically diagnosed meningioma located at BS or in frontal areas, before radiotherapy prescribed in our center’s multi- disciplinary meeting. Further evaluation of IHC prescreening using GAB1 and OTX2 was also conducted. Results: -61 patients were included: 61.66% (N=36) in BS with median age 53 while 80.33% (N=47) were female. 62% (N=38) were grade 1, 35% (N=21) were grade 2 and 3% (N=2) grade 3. -2 (3%) meningiomas displayed a SMO mutation and 4 (6%) men- ingiomas a PIK3CA mutation. Five (83%) meningiomas with SMO or PIK3CA mutations were grade I. -Among the 8 cases (16%) that express GAB1 with a H-score >120, 2 were associated with SMO and 1 with PIK3CA mutation. OTX2 expression was contributive. - All AKT mutated meningiomas (N=9,100%) , displayed a GAB1 H-score < 120, a score considered as negative. Conversely GAB1 was expressed in SHH activated meningiomas. Conclusion: -In real life clinical situation we showed that SHH and mTOR activating mutations are rarer than previously described in exhaustive “molecular landscape” studies. These new data should be taken in account for future therapeutic trial designs. -GAB1 could be a useful marker for immunohistochemical pre- screening of cases amenable to sequencing for hedgehog pathway or mTOR pathway genes sequencing while OTX2 is not a benefi- cial marker. -The WHO grading system has no role in predicting tumour molec- ular alterations of meningiomas. OFP-13-011 miR-196b-5p and miR-107 expression differentiates ocular sebaceous carcinoma from squamous cell carcinoma of the conjunctiva R.M. Verdijk*, R.O. de Keizer, A. Vriends, G.J. Hötte, D..A. Pari- daens, E.A. Wiemer *Erasmus MC University Medical Center Rotterdam, The Netherlands Background & objectives: Ocular Sebaceous Carcinoma (OSC) can mimic Squamous Cell Carcinoma of the Conjunctiva (SCCC). Aim of this study was to find microRNA biomarkers to distinguish OSC and SCCC from normal tissue and from each other. Methods: Clinical OSC and SCCC case files and corresponding histopathological slides were collected and reviewed. Microdis- sected formalin-fixed paraffin-embedded tumour and control tissue were subjected to semi-high throughput microRNA profiling. Results: MicroRNA expression distinguishes OSC and SCCC from corresponding control tissues. Selected differentially expressed miRNAs were validated using single RT-PCR assays. A comparison between OSC (n=14) and SCCC (n=18) revealed 38 differentially expressed microRNAs (p<0.05). Differentially expressed miRNAs were selected for validation in the discovery cohort and an independent validation cohort (OSC, n=11; SCCC, n=12). At least two miRNAs miR-196b-5p (p ≤ 0.05) and miR-107 (p ≤ 0.001) displayed a statistically significant differential expression between OSC and SCCC with miR-196b-5p upregulated in SCCC and miR-107 upregulated in OSC. ROC analyses indicated that the combined miR-196b-5p and miR-107 expression lev- els predicted OSC with 90.0% sensitivity and 83.3% specificity. Conclusion: Our findings indicate that deregulated miRNAs, identified by comparing tumour tissue with corresponding control tissue, may play a role in the tumourigenic processes in OSC and SCCC. We provide evidence that miR-196b-5p and miR-107 can differentiate OSC from SCCC. Combined testing of miR-196b-5p and miR-107, may be of additional use in routine diagnostics to discriminate OSC from SCCC in conjunctival tumour lesions. Funding: This research was funded by SWOO-Flierenga, grant number SSWOO2018S12 OFP-13-012 Audit of outcomes for metastatic uveal melanoma patients in Ireland C. Hegarty*, K. Kulakova, N. Walsh, C. Hui, S. Kennedy * Research Foundation, Royal Victoria Eye and Ear Hospital, Dublin, Ireland Background & objectives: Uveal Melanoma (UM) accounts for approximately 85% of ocular melanomas. The published rate of metastasis is approximately 50%, 5 years following diagnosis. This retrospective analysis investigated the percentage of patients who metastasised and their outcome over a 21 year period. Methods: A detail review of pathology files, cancer registry files and death certs were accessioned, and results were tabulated on excel. UM patients who received enucleation were selected and further analysis was used to determine who presented with metas- tasis. Prior to 2011 patients were treated by enucleation. From 2011 on patients were treated by either plaque rt, proton beam or enucleation. Results: From 194 identified metastatic cases, 93 were female and 101 male. Patient age ranged from 11-90 (average age: 62) at initial diagnosis. 10 patients were aged 20-40, 61 aged 40-60, 112 aged 60-80 and 17 aged 80-100. Youngest patient in this cohort was 11 and metastasised and died shortly after diagnosis. Primary tumour location: choroid and ciliary body. Average time for metastasis was 44 months. S55