ECP 2023 Abstracts

S8 Virchows Archiv (2023) 483 (Suppl 1):S1–S391 13 guidelines. The study aims to evaluate the impact of integrated molecu- lar and pathologic risk stratification and the relevance of pathologic parameters in predicting prognosis in each molecular subgroup. Methods: ECs were classified using immunohistochemistry and next- generation sequencing into the four molecular classes: POLE mutant (POLE), mismatch repair deficient (MMRd), p53 mutant (p53abn), and no specific molecular profile (NSMP). Results: According to WHO algorithm, 219 ECs were subdivided into the following molecular subgroups: 7.2% POLE, 32.8% MMRd, 21% p53abn, 39.2% NSMP. Molecular classes as well as pathological parameters and ESGO/ESTRO/ESP 2020 risk groups were statistically correlated with disease-free survival. At multivariable analysis, the independent parameters associated with recurrence for the entire cohort were: stage, grade, and tumour budding. Refining the analysis to NSMP tumours, several pathological features were correlated with recurrence: histotype, grade, stage, necrosis, tumour budding and substantial lym- phovascular space invasion (LVSI). At multivariable analysis in NSMP subgroup, the independent parameters predictive of recurrence were: necrosis and tumour budding. Conclusion: Our study supports the prognostic importance of EC molecular classification and demonstrated the essential role of accurate assessment of pathological parameters predictive of recurrence that are still crucial for appropriate patient management. OFP-02-008 Endometrial stromal sarcomas with BCOR alterations: clinico- pathological and molecular study of a rare subgroup C. Alves-Vale*, M. Varela dos Santos, N. Maida Méndez, C. Martins, F. Silva, S. Lérias, A. Felix, J. Ferreira *CUF Descobertas Hospital, Faculdade de Medicina da Universidade de Lisboa, Portugal Background & objectives: Endometrial stromal sarcomas (ESS) are rare uterine neoplasms. BCOR alterations occur in a small subset of those. MDM2 and CDK4 pathway alterations have recently been described. We review the clinicopathological and molecular features of a series of ESS with BCOR alterations. Methods: Four BCOR -associated ESS were retrieved: one with BCOR internal tandem duplication ( BCOR -ITD) and three with BCOR rear- rangements ( ZC3H7B rearranged in 2 cases; no rearrangements of MAML3 , CCNB3 , or JAZF1 detected). Clinical, morphological and immunohistochemical data were collected and reviewed. Compara- tive genomic hybridization (CGH) was performed, followed by FISH analysis of MDM2 , CDK4 , CDKN2A , and RB1 genes in selected cases. Results: Age at diagnosis ranged from 49 to 71y. FIGO stages were IA, IB and IVB. Neoplasms were myxoid and composed of round-to-spindle cells, with mitotic activity: 3-12/mm2. Collagen plaques (3/4), staghorn- shaped vessels (3/4), lymphovascular invasion (2/4) and necrosis (2/4) were found. Tumours showed an infiltrative pattern or a tongue-like infil- tration with intravascular plugs. CD10 expression was strong and diffuse ( BCOR -rearranged ESS) or focal and weak ( BCOR -ITD). Cyclin D1 positivity was variable (60-90%). In two cases, CGH analysis revealed gain of 12q13-q21.1, corresponding to MDM2 / CDK4 amplification (con- firmed by FISH), and deletions affecting 9p and 13q (with corresponding CDKN2A and RB1 deletion by FISH). Despite different follow-up dura- tions (1-42mo), outcomes varied from disease-free to death. Conclusion: Our cases present several similarities to those previously described, namely the myxoid background, frequently with staghorn- shaped vessels. The case without ZC3H7B rearrangement shares mor- phology and immunoprofile with ZC3H7B-BCOR rearranged neoplasms. We also detected a subset of cases with MDM2 and CDK4 amplification, along with CDKN2A and/or RB1 deletion. This emphasizes the clinical relevance of detailed molecular characterization of BCOR -associated ESS to identify potential candidates to CDK4/6 inhibitors. OFP-02-009 Genomic profile analysis of leiomyomas with bizarre nuclei and fumarate hydratase deficient leiomyomas: strengths, weaknesses, and limitations of array-CGH interpretation Q. Fontanges*, P. Dubos, T. Lesluyes, Y. Laizet, V. Velasco, L. Mayeur, E. Oliva, R.H. Young, M. Devouassoux-Shisheboran, S. Isabelle, G. Frédéric, J.C. Noël, M. Barbara, F. Chibon, S. Croce *Cliniques Universitaires de St Luc, Belgium Background & objectives: Array-CGH analysis of uterine smooth muscle tumours is becoming part of diagnosis routine. The aim of this study is to investigate the genomic profiles of two challenging leiomy- oma variants: leiomyoma with Bizarre Nuclei (LMBN) and Fumarate Hydratase deficient leiomyoma (FHLM). Methods: Genomic profiles of 28 FHLM and 37 LMBN from 64 patients were analysed by array-CGH. Genomic complexity was evalu- ated from a quantitative (Genomic Index (GI)) and qualitative (tumour suppressor gene analysis) perspective. Clinical data included patient’s age, type of surgery and follow-up. We tested 9 tumours with Nanocind CINSARC®, a transcriptomic signature reflecting genomic complexity and demonstrated to be prognostic. Results: Follow-up was available for 46 patients (mean 87,3 months). All were alive without disease. For 51 array-CGH interpretable tumours, mean GI was 16.4, lower than LMS (mean GI 51.8, p<0.001). Three groups emerged: 1) FH deleted (24/58) with low GI (mean 11), 2)TP53 deleted (17/58) with higher GI (mean 22.4), and 3)no event on FH or TP53 (17/58) (mean 18.3). FH deleted and TP53 deleted genomic groups were associated with distinct clinical and pathological profiles. Patients harbouring FH deletion were younger than those with TP53 deleted tumour (mean 44,1 y. vs 51,8 y., p=0.006. The 9 tested tumours were classified C1 with Nanocind CINSARC® signature (low- est risk of recurrence). Conclusion: Our findings indicate that a GI>10 or alterations in tumour suppressor genes in isolation should not warrant a diagnosis of malignancy and can be observed among LMBN and FHLM with long follow up and no recurrences. Although a GI <10 remains a pre- dictor of benign behaviour, the GI at the cut off of 10 is not applicable in these LM variants. LMBN and FHLM are challenging entities, GI and genomic profile should be interpreted with caution in these mor- phological settings. OFP-02-010 Diagnostic value of pan-TRK immunohistochemistry in NTRK- rearranged gynaecological sarcomas and morphological mimics. A study of 473 gynaecological mesenchymal tumours S. Croce*, M. Souto, V. Velasco, F. Kommos, E. Oliva, I. Treilleux, M. Devouassoux-Shisheboran, I. Hostein, I. Soubeyran, E. Khalifa, G. Mccluggage, C. Hartog, F. Le Loarer, J. Costa *Institut Bergonié, France Background & objectives: NTRK-rearranged sarcomas of the uterus show a “fibrosarcoma-like” morphology, harbour NTRK rearrange- ments and they strongly express pan-TRK. The aim of this study is to investigate pan-TRK immunohistochemistry in a large cohort of gynaecological mesenchymal neoplasms, including NTRK-rearranged sarcomas and mimics. Methods: A total of 473 gynaecological mesenchymal tumours (461 without NTRK fusions and 12 NTRK-rearranged sarcomas) were included. Pan-TRK immunohistochemistry (EPR17341, Abcam on Ventana Benchmark platform) was performed on whole tissue sections and tissue microarrays. Molecular study of pan-TRK positive tumours was performed by RNA sequencing or FISH. Results: Of the 12 NTRK-rearranged sarcomas, 11 (92%) exhib- ited pan-TRK staining, mostly diffuse (≥70%) and cytoplasmic with