ECP 2023 Abstracts

S93 Virchows Archiv (2023) 483 (Suppl 1):S1–S391 13 PS-10-030 Risk stratification of endometrioid endometrial carcinoma (EEC) of no specific molecular profile (NSMP) utilizing E2F1 and CCNA2 RNA expression and PPP2R1A/FBXW7 mutation status M. Shahi*, S. Yadav, S. Jenkins, J. Bakkum-Gamez, N. Kanwar, J. Gonzalez Bosquet, K. Halling, K. Podratz *Mayo Clinic, USA Background & objectives: NSMP molecular subgroup consists of EEC with predominantly FIGO grade 1/2 histology with at least intermediate risk of recurrence. Intermediate/high-risk disease in histomorphologic low-grade EEC imposes prognostic/therapeutic challenges. We assessed the performance of a novel molecular risk-classifier in NSMP EEC. Methods: The Cancer Genomic Atlas (TCGA) data was utilized. Three molecular profiles (MP) within the NSMP subgroup (N=89) were evaluated and correlated with clinical outcomes: MP1- E2F1+CCNA2 log2 expression low (L) (<4.75); MP2-. E2F1+CCNA2 log2 expression high (H) (≥4.75); and MP3- PP2R1Amu/FBXW7mu. Tumour grade, stage, L1CAM log2 expression, and CTNNB1mu, PIK3CAmu, ARID1Amu, KRASmu were studied in each MP. Results: The 3-year recurrence free survival (RFS) for MP1, MP2 and MP3 was 93.6%, 36.7% and 61.1%, respectively; corresponding Cox univariate hazard ratios for recurrence(95% CI) were 14.329 for MP2 (3.6, 71.5) and 9.7 for MP3 (2.1, 49.6) respectively (MP1 reference, overall P=0.0002). No significant associations with PFS were found in univariate analysis of tumour grade, stage, L1CAM expression tertile, CTNNB1mu, PIK3CAmu, ARID1Amu, or KRASmu. RFS in FIGO grade 1 EEC with <75% Myoinvasion and MP1 vs. MP2/MP3 was 100% vs. 49.3%, respectively (p<0.0001). Conclusion: We present molecular profiles (E2F1+CCNA2-H and FBXW7mu/PPP2R1Am vs. E2F1+CCNA2-L) that i) selectively identifies occult high-risk disease among histomorphologic low-grade EEC, ii) efficiently risk-stratified TCGA NSMP EEC, and iii) suggests potential value in molecular-surgical staging. PS-10-031 Endometrial clear cell carcinoma mimickers (CCCM): morpho- logic, immunophenotypic and molecular evaluation of an enigmatic and diverse group of tumours M. Shahi*, F. Reyes-Baez, K. Schoolmeester, M. McGree, A. Fought, L. Grcevich, G. Schivardi, G. Glaser, A. Mariani *Mayo Clinic, USA Background & objectives: Endometrial clear cell carcinoma (ECCC) is associated with aggressive behaviour. Besides its diverse molecular land- scape and clinical behaviour, controversy regarding risk stratification can be due to overdiagnosis. A subset of non-ECCC (CCCM) exhibits histo- logic characteristics resembling ECCC, imposing diagnostic difficulties. Methods: Cases diagnosed as ECCC or carcinoma with clear cell changes (1999-2017) were re-examined by two gynaecologic pathologists and re- classified as ECCC and CCCM. Histologic [histotype, grade, myoinva- sion, LVSI, peritumoral stromal tumour-infiltrating lymphocytes (sTILs)], IHC assessment [p53, mismatch repair (MMR) proteins and L1CAM] and POLE sequencing performed. Overall and Progression-free survival (OS/PFS) of CCCM and ECCC per molecular subclass were evaluated. Results: Upon curated pathology review, 37 of 125 (29.5%) cases were reclassified as CCCM, further classified as high-grade (n=14) (including serous, FIGO grade 3 endometrioid carcinoma with clear cell changes and yolk sac tumour) and low-grade morphology (n=23) including FIGO grade 1 and 2 endometrioid carcinoma with clear cell changes. CCCMs are enriched with MMRd (n=16/35, 46%), followed by NSMP (n=11/35, 31%) and p53abn (n=8/35, 23%). No pathologic POLE mutations were identified. MMRd cases demonstrated a higher rate of extensive LVSI (7/16 vs. 3/19) and more extensive sTIL (mean 2.3 vs.1.6). The prognosis of NSMP was significantly better in CCCM vs. ECCC (90% vs. 54% OS at 5-year). Conclusion: CCCM is composed of morphologically, biologically and prognostically heterogeneous groups of cases enriched with MMRd molecular subclass. Comprehensive pathologic assessment for the segregation of this group from the unequivocal ECCC is necessary for better risk stratification of such patients. PS-10-032 Vitamin E inhibits heavy metals accumulation in the uterus during short- and long-time exposure K. Sikora*, Y. Lуndіna, N. Hyriavenko, A. Awuah Wireko, T. Abdul- Rahman, D. Tsepochko, O. Romaniuk, M. Lyndin, A. Romaniuk *Sumy State University, Ukraine Background & objectives: Vitamin E demonstrates benefits for repro- ductive health protection against pollutants. Therefore, we aimed to study the protective effect of vitamin E treatment on the heavy metals (HMs) accumulation in rats’ uterus under 30 and 90 days of HMs exposure. Methods: Female rats were randomly divided into three groups: untreated animals (control group); animals orally treated with HMs (Zn,Cu,Fe,Mn,Pb,Cr) mixture (HM group); and animals treated simulta- neously with HMs and vitamin E (HM+E group) during 30 and 90 days. The chemical composition of uteruses was studied by Scanning-electron microscopy with elemental analysis and atomic absorption spectrometer. Results: Our previous results demonstrated a considerable (p<0.01) bio- accumulative potential of Zn, Cu, Fe, Mn, Pb, and Cr in the rat uterine within 30 and 90 days in the HM group compared to the control. Here- with, HMs levels in the HM+E group were also significantly (р<0.01) higher on the 30th and 90th days (Zn–x1.18/1.29, Cu–x1.31/1.46, Fe– x1.45/1.59, Mn–x1.26/1.45, Pb–x1.39/1.62, Cr–x1.36/1.56) compared to control. Combining all the results, vitamin E treatment showed a decrease (р<0.01) in HMs accumulation on x1.12/1.13 for Zn, x1.1/1.09 for Cu, x1.11/1.15 for Fe, x1.09/1.12 for Mn, x1.09/1.14 for Pb, x1.08/1.1 for Cr in the uterus against to HM group, respectively. Conclusion: Vitamin E has not provided complete protection against HMs accumulation. However, this treatment significantly reduced the bioaccumulative potential of pollutants. Moreover, the positive effect of vitamin E was confirmed by the intensity reduction of Zn, Cu, Fe, Mn, Pb, and Cr accumulation with the treatment prolongation to 90 days. PS-10-033 Incidence of high-risk and low-risk human papilloma virus sub- types in invasive squamous cell carcinomas of the cervix: a molecu- lar international multi-institutional study on 448 cases S. Stolnicu*, D. Allison, A. Momeni Boroujeni, L. Hoang, C. Ter- inte, A. Pesci, C. Mateoiu, R.R. Lastra, T. Kiyokawa, R. Ali-Fehmi, M. Kheil, E. Oliva, K.M. Devins, N.R. Abu-Rustum, R.A. Soslow *Department of Pathology, UMFST Gh E Palade of TarguMures, Romania Background & objectives: Squamous carcinoma of the cervix (SCC) is the fourth most common malignancy to affect women worldwide, historically attributed to High-risk Human Papil- loma Virus (HR-HPV) infection. We aimed to determine the inci- dence of HR-HPV and Low-risk HPV (LR-HPV)-associated SCCs. Methods: 448 surgically treated (conization/trachelectomy/hysterec- tomy) SCCs with readily available tissue to construct tissue microar- rays were retrospectively assessed to confirm the microscopic diagno- sis, tumour growth patterns, associated precursor lesion and further studied by in situ hybridization for HR-HPV and LR- HPV. Cases were considered as positive for either HR- or LR-HPV if any nuclear or cytoplasmatic signal was encountered within tumour cells. Results: A total of 10 (2.2%) HPV-independent (HPVI) SCCs and 437 (97.8%) HPV-associated (HPVA) SCCs were identified with significant