ECP 2022 Abstract Book

Virchows Archiv (2022) 481 (Suppl 1):S1–S364 13 of sub-cluster B2 showed significantly better overall survival compared to the others three subgroups (p=0.040). Conclusion: Endometrial carcinoma is a complex disease with a spectrum of different genomic and epigenetic alteration profiles. Our findings support that methylation analysis has the potential to predict molecular and clinical variables. Further analysis of the impact of specific differentially methylated regions on clin- icopathologic variables is ongoing. 1 Both authors contributed equally 2 Co-senior authors OFP-02-007 Integrated clinicopathological and molecular analysis of endometrial carcinoma: prognostic impact of the new ESGO- ESTRO-ESP endometrial cancer risk classification A. De Leo*, A.G. Corradini, F. Rosini, J. Lenzi, M. Grillini, M. Ruscelli, M. Errani, T. Maloberti, S. Coluccelli, G. Tallini, D. Santini, C. Ceccarelli, D. de Biase *Pathology Unit, University of Bologna Medical Center, Italy Background & objectives: The ESGO/ESTRO/ESP committee has been recently proposed a new risk stratification system for endometrial cancer (EC) patients incorporating both clinico- pathological and molecular characteristics. The study aims to compare the ESGO/ESTRO/ESP risk classification system with the previous 2016 risk classification. Methods: The cohort included 187 consecutive patients with endo- metrial carcinoma. Immunohistochemistry (IHC) and Next-Gen- eration Sequencing (NGS) were used to assign TCGA molecular EC subgroups: POLE mutant (POLE), mismatch repair deficient (MMRd), p53 mutant (p53abn), and no specific molecular profile (NSMP). Results: TCGA class assignment of EC cohort: 7% POLE group, 31% MMRd group, 23.5% p53abn group, 38.5% NSMP group. In the 2020 risk classification system, 39.1% of patients were allo- cated to low risk compared with 22.6% in the 2016 risk classifica- tion system, mainly due to reclassification of patients previously classified especially as high-intermediate risk. The recent 2020 guidelines revealed a total of 61 patients (32,6%) with a change in risk group in relation to the 2016 classification system: the shift was due to p53abn, POLE alterations and lymph vascular inva- sion. The application of the 2020 risk stratification system shows Kaplan-Meier curves with a more significant difference between the groups throughout survival. Conclusion: In our cohort, the application of the new 2020 risk classification integrating clinicopathological and molecular param- eters provided a more accurate identification of low-risk and high- risk patients, potentially allowing a more specific selection for post-operative adjuvant therapy. Integrated molecular classification is a promising tool for a better therapeutic management of patients. OFP-02-008 CCND1 amplification and cyclin D1 overexpression correlate with adverse outcome in vulvar squamous cell carcinoma N. Carreras-Dieguez, C. Manzotti, M. del Pino, I. Trias, I. Ribera- Cortada, S. Diaz-Mercedes, L. Marimon, N. Vega, M.T. Rodrigo, J. Ordi, N. Rakislova* *Hospital Clínic Barcelona, Spain Background & objectives: There is scarce evidence regarding the role of CCND1 amplification and protein overexpression in vulvar squamous cell carcinomas (VSCC). We aimed to 1) correlate cyclin D1 DNA amplification with protein overexpression and 2) correlate cyclin D1 overexpression with clinical prognosis. Methods: Whole exome sequencing and cyclin D1 immunohis- tochemistry (IHC) were performed in 65 VSCC. Copy number alterations were predicted for the tumour-control pairs using Con- trolfreeC. The prognostic significance of cyclin D1 IHC overex- pression and its correlation with clinical-pathological features was further assessed in a subset of 90 VSCC. Cyclin D1 was considered overexpressed when >50% of the tumour cells stained positive. Results: A total of 18/65 (27.6%) VSCC showed amplifications in CCND1 and 26/65 (40.0%) showed strong cyclin D1 overexpres- sion. A strong positive correlation between CCND1 amplification and cyclin D1 overexpression was found (p<0.001). Both CCND1 gains and cyclin D1 overexpression strongly correlated with worse disease-free survival (p<0.001 for each). Only cyclin D1 IHC over- expression had significant association with worse disease-specific survival (p<0.01). In the cohort of 90 VSCC, tumours overexpressing cyclin D1 showed worse disease-specific and disease-free survival than cyclin D1-negative tumours (p<0.001 for each). Cyclin D1 overexpression correlated also with HPV-negative status (p<0.001), presence of p53 abnormalities (p<0.001) and advanced FIGO stage [III-IV vs. I-II] (p=0.02). Conclusion: Our findings indicate that CCND1 is amplified and overexpressed in a significant proportion of VSCC, mostly in HPV- independent tumours. Cyclin D1 overexpression is strongly asso- ciated with adverse patient outcome (worse disease-specific and disease-free survival) and could be a useful tool for prognostic stratification. Innovative targeted therapies could be explored based on these findings. Funding: Project “PI20/00368; Caracterización genómica de los carcinomas de vulva independientes de virus del papiloma humano y de sus precursores”, funded by Instituto de Salud Carlos III and co-funded by the European Union (ERDF) “A way to make Europe”. ISGlobal receives support from the Spanish Ministry of Science and Innovation through the “Centro de Excelencia Severo Ochoa 2019-2023” Program (CEX2018-000806-S), and support from the Generalitat de Catalunya through the CERCA Program. OFP-02-009 Worse disease-free survival for patients with vulvar squamous cell carcinoma arising on HSIL-like or VAAD/DEVIL lesions N. Rakislova*, N. Carreras-Dieguez, C. Pumarola, M. del Pino, C. Manzotti, A. Saco, I. Trias, I. Ribera-Cortada, M.T. Rodrigo, S. Diaz-Mercedes, R. López del Campo, L. Marimon, J. Ordi *Hospital Clínic Barcelona, Spain Background & objectives: A number of new precursors of Human Papillomavirus (HPV)-independent vulvar squamous cell carcino- mas (VSCC) have been recently defined: vulvar acanthosis with altered differentiation (VAAD), differentiated exophytic intraepi- thelial lesions (DEVIL) and high-grade squamous intraepithelial (HSIL)-like lesions. Methods: We assessed whether patients with HPV-independent VSCC had any clinico-pathological differences depending on the associated adjacent precursor. The study comprised 157 patients with HPV-independent VSCC surgically treated between 1975 and 2021. The skin adjacent to the tumour was histologically reviewed. The median follow-up was 69 months. Correlations with outcome were analysed using multivariable Cox regression and log-rank analysis. Results: 50 patients (31.8%) showed differentiated VIN (dVIN), 49 patients (31.2%) showed adjacent inflammatory dermatosis, 25 (15.9%) had HSIL-like lesions, 9 (5.7%) showed VAAD or DEVIL and in 24 women (15.3%) no adjacent skin lesion was identified. Patients with HSIL-like and VAAD/ DEVIL lesions showed impaired disease-free survival (higher S8