ECP 2022 Abstract Book

Virchows Archiv (2022) 481 (Suppl 1):S1–S364 13 S. Antunes*, C. Dahlstedt Ferreira, R. Oliveira, D. Gomes Pinto *Hospital Garcia de Orta, Portugal Background & objectives: Endometrial cancer (EC) is the most com- mon gynaecological malignancy in developed countries. By analysing intraoperative consultation (IOC) of EC cases, we want to assess our performance so far, aiming at determining the best approach for these cases. Methods: We identified all cases of EC that underwent IOC, over the last 7 years at out institution. Data were gathered from pathology reports and patients’ clinical files. We focused on analysing the purpose of the IOC (diagnosis vs. staging), if frozen sections were performed, concordance of intra-operative with definitive diagnosis and how this result influenced the surgical procedure. Results: Seventy-eight IOC in endometrial lesions were performed, 75 for staging and 3 for diagnosis. The average age of the patients was 67 years. Sixty-four (82,05%) cases were concordant, eleven (14,1%) were discordant and three (1,85%) were deferred. Twenty- seven IOC had frozen sections performed. Four discordant cases were upstaged in the surgical specimen due to myometrium invasion, two due to cervical stromal invasion and four due to serosa and/or adnexal involvement. No frozen sections were performed in the lat- ter. There were no statistically significant differences between cases with and without frozen section (p=0,7362) in terms of concordance. Conclusion: At our institution, concordance between IOC and definitive diagnosis is high, with only seven discordant cases (8,97%) with impact on the patient. Out results show that gross evaluation is mostly adequate for staging EC, but frozen sections might be of particular use on grossly borderline cases for myo- metrial and cervical stromal invasion. Serosal or adnexal nodules should be detected grossly, and frozen sections performed. IOC is useful in cases of EC, eliminating the need for reintervention in many patients. PS-08-038 PD-L1 and mismatch repair (MMR) protein expression in small cell carcinomas of the uterine cervix R. Moiteiro da Cruz*, J. Almeida-Tavares, S. Lérias *Department of Pathology - Hospital de Santa Maria, CHULN; Faculdade de Medicina da Universidade de Lisboa, Portugal Background & objectives: Cervical neuroendocrine carcinoma(NEC) is rare with limited therapeutic options. Recent studies described abnormal p53, MMR deficient and PD-L1 expression in cervical NECs. Our aim was to evaluate p53, PD-L1 and MMR protein expression in NECs and its correlation to prognosis. Methods: We selected 5 cases of NECs with known clinicopatho- logical and prognosis data diagnosed over 22 years(2000 to 2022). Immunohistochemistry for p53, p16, PAX8, chromogranin, syn- aptophysin, TTF-1, PD-L1(22C3 clone) and MMR proteins was performed. PD-L1 was assessed using the combined positive score(CPS) with a threshold of ≥1 required for positivity and aber- rant p53 (overexpression or null) was considered positive. Results: Mean patient age was 58 years (range 33-71), all cases were diagnosed in FIGO stage IV and 2 died of disease. Three cases were pure small-cell NEC and 2 were mixed carcinomas, associated with adenocarcinoma (n=1) and squamous cell carci- noma (n=1), each. All cases demonstrated p16 positive staining, synaptophysin focally positive staining, chromogranin negative staining and PD-L1 negative. PAX8 was positive in 4 cases, TTF-1 in 3 cases, p53 mutant pattern was observed in 3 cases and no MMR deficiency was observed. Conclusion: Our study showed strong nuclear staining for p16 in all cases, demonstrating the influence of high-risk HPV infection on its carcinogenesis. The variability of p53 expression demon- strate the diversity of genomic landscape of this tumour, being in accordance with the most common genetic alterations usually found. No expression of PD-L1, as well as no MMR deficient was found, suggesting a lower expression of PD-L1 in tumours with microsatellite stability. PS-08-039 Polymerase-ɛ exonuclease domain mutations predict excel- lent outcome among SWI/SNF-deficient undifferentiated and dedifferentiated endometrial carcinomas B. Tessier-Cloutier*, M. Köbel, A. Momeni-Boroujeni, J. Ben- hamida, C. Stewart, M. Ladanyi, R. Soslow, C. Lee *Memorial Sloan Kettering Cancer Center, USA Background & objectives: SWI/SNF-deficient undifferentiated (UDEC) and dedifferentiated (DDEC) endometrial carcinomas are aggressive malignancies with poor treatment response. The prognostic role of the molecular classification is unknown in those malignancies. Here we review a molecularly and clinically annotated series of SWI/ SNF-deficient UDEC/DDEC. Methods: We collected a series of UDEC/DDEC with loss of expression of a core SWI/SNF protein (SMARCA4, SMARCB1, or ARID1B). The molecular subtype was assigned according to the Proactive Molecular Risk Classifier for Endometrial Can- cer (ProMisE), including hotspot POLE mutation testing and immunohistochemistry for mismatch repair proteins and p53. Kaplan Meier survival analysis was performed across all differ- ent molecular subgroups. Results: We included 60 UDEC/DDEC, the median age of the cohort was 59 years (range: 37-82 years) and most cases were high stage at presentation (19/36). Of the 60 cases, 36 were MMR-deficient (MMR-d), 6 were POLE mutated ( POLE mut), 4 p53 abnormal (p53abn) and 14 with no specific molecular profile (NSMP). The median overall survival of POLE mut cases was 26.1 months without any death, compared to 11.8 months in the rest of the cases (p=0.034). The cases classified as MMR-D, p53abn or NSMP had similar outcome (p=0.319). Conclusion: All POLE mut cases had an excellent prognosis while the other three molecular subgroups (MMR-D, p53abn and NSMP) had poor outcomes. Molecular classification among the non- POLE mut cases was not informative of clinical behaviour in our study. These results highlight the importance of hotspot POLE mutation testing in SWI/SNF-deficient UDEC/DDEC to help guide management. PS-08-040 Contribution of Forkhead box A1 to endometrial cancer progression E. O’regan*, Z. Greally, P. Lewitowicz, O. Adamczyk-Gruszka, A. Horecka-Lewitowicz, J. Gruszka, A. Strzelecka *Jan Kochanowski University in Kielce, Poland Background & objectives: Investigate the influence of Forkhead-box on endometrial cancer progression. The molecular subgrouping of EC proposed by the Cancer Genome Atlas is vital in precise molecular- based patient triage. The driving mechanisms are necessary to identify correlations between genes and their regulators. Methods: A total of 103 White female patients with confirmed EC were enrolled. For analysis, we used next-generation sequencing S116