ECP 2022 Abstract Book

Virchows Archiv (2022) 481 (Suppl 1):S1–S364 13 Conclusion: A new HRD solution beyond BRCA1/2 mutation detection provides expanded clinical information and improves the diagnostic yield of HRD in OC. This could be useful for personal- ized OC treatment. PS-08-029 Influence of histological and immunohistochemical features of endometrioid adenocarcinoma on the microvascular tumour density M. Lyndin*, O. Kravtsova, V. Sikora, N. Hyriavenko, Y. Lyndina, Y. Soroka, R. Moskalenko, A. Romaniuk *Sumy State University, Ukraine Background & objectives: Endometrioid adenocarcinomas of the uterine body account for about 70-80% of all endometrial carcino- mas. The most proven prognostic markers are age, stage of the disease, histological grade, microvascular density (MVD), and expression of prognostically important receptors. Methods: The investigation was conducted on 30 samples of endo- metrioid adenocarcinomas. The presence of E-cadherin, VEGF, ER, PR, Ki-67, and р53 was detected by immunohistochemistry. Results: The pronounced predominance of MVD in moderately and low-differentiated tumours over highly differentiated endometrioid adenocarcinomas was found (F=6.34, p=0.0055). A positive correlation was found between MVD and the expression of VEGF (r=0.47, p=0.0086) and Ki-67 (r=0.54, p=0.0023) in tumour cells; a negative – between MVD and PR (r=-0.45, p=0.012). Expression of ER, E-cadherin, and p53 had no effect on the MVD of neoplastic tissues (p>0.05). Conclusion: The neovascularization degree and microvascular density of endometrioid endometrial adenocarcinoma tissues are enhanced by tumour dedifferentiation and VEGF overexpression. There is a positive correlation between the proliferative activity level of tumour cells and MVD; a negative – between the expres- sion of PR and MVD. PS-08-030 Germline and somatic BRCA1 and BRCA2 mutational analy- sis in non-mucinous ovarian carcinomas. A retrospective and descriptive study of 80 cases A.B. Moreno García*, I. Costa Trachsel, C.M. Blázquez-Mañá, A. Reques Llanos, R. Carrera-Salas, M.J. Martinez Reyes, A. Falgueras i Sanchez, M.d.C. Ramos-Guijo, Y. Garcia Garcia, L. Ribot Luna, A. Ruiz Nel·lo, J.C. Ferreres Piñas *Department of Pathology. Parc Taulí Hospital Universitari. Sabadell; Institut de Recerca i Innovació Parc Taulí (I3PT), Uni- versitat Autónoma de Barcelona, Spain Background & objectives: BRCA1 and BRCA2 somatic or germline mutations in ovarian cancer (OC) have familial, prognostic and pre- dictive significance. We analysed the mutational status of these genes in our cohort of patients and its correlation with several clinical and pathological parameters. Methods: Next-generation sequencing of BRCA1 and BRCA2 was performed in 80 patients with non-mucinous OC, in tumour and peripheral blood, from January 2019: 62 high-grade serous (HGSC), 8 low-grade endometrioid, 3 high-grade endometrioid (HGECC), 4 clear cell (CCC), 1 low-grade serous carcinomas, 1 carcinosarcoma and 1 borderline serous tumour. Age, FIGO stage, histological type, clinical behaviour and molecular features were collected. Results: Twenty-five pathogenic variants(PV) in 23/79 tumour- samples (30%) were detected: 16 BRCA1/ 9 BRCA2; 15 germinal(g) (60%) and 5 (20%) somatic(s) (5 blood pending); 16 "frameshift", 5 "nonsense", 3 "missense" and 1 "splicing” (identi- cal results in germinal confirmed cases). Somatic medium allelic frequencies(AF) were 28% versus 68% in germinal cases. One addi- tional germinal (no tumour analysis available) was detected. 22 were HGSC (15 BRCA1/7 BRCA2), one CCC (gBRCA1/sBRCA2), and one HGECC (BRCA1/ BRCA2, blood pending, tumourAF 54%/70%). BRCA mutated-patients were 55.7yo-medium and 20% stage I-II, at diagnosis; non-mutated were 65.5yo and 25% I-II. All BRCA mutated-patients are alive, 40% with no disease(AWND); 12% of non-mutated-patients are exitus and 20% are AWND. Conclusion: The mutational study of BRCA1/BRCA2 in tumour- tissue is cost-effective, sensitive and specific for germinal and somatic line PV detection. Germinal, “frameshift” type and HGSC are the prevalent mutation-line, PV and histologic type, respec- tively. PV in tumour and blood in germinal confirmed cases were identical. Mutated cases are associated with younger onset age patients and better clinical behaviour, compared to non-mutated cases. This analysis is essential for an optimal management and for individual and family counselling. PS-08-033 Uterine smooth muscle tumours of uncertain malignant poten- tial (STUMPs) with fumarate hydratase deficiency: report of 2 cases C. Alves-Vale*, A. Beltran, A. Alves *CUF Descobertas Hospital, Portugal Background & objectives: Fumarate hydratase (FH) deficiency accounts for characteristic architectural and cytological features, which may result in erroneous classification of uterine neoplasms if not recognised. We report 2 cases of FH-deficient smooth muscle tumours of uncertain malignant potential (STUMPs), diagnosed after myomectomy. Methods: Case 1 refers to a 42-year-old woman presenting with a solitary uterine transmural nodule with 95 mm, without relevant personal or family history. Case 2 refers to a 27-year-old woman, with multiple uterine nodules since the age of 21 and family history of “leiomyomas”, the largest with 111 mm, refractory to ulipristal acetate therapy. Results: Microscopically, both tumours were composed of a spin- dle cell proliferation with focal areas of alveolar-type oedema and frequent vessels, sometimes with hemangiopericytoma-like pat- tern. Moderate to severe atypia was observed, including bizarre nuclei or prominent nucleoli with perinucleolar halo. Cytoplasm was eosinophilic, with rhabdoid inclusions focally. Immunore- activity for FH was lost. Mitotic index was lower than 4/mm2. Necrosis of indeterminate nature was present in the first case, and both tumour cell necrosis and ischemic-type necrosis were detected in the second. The diagnosis of FH-deficient STUMP was made. Patients were referred to the Genetics consultation to exclude FH germline mutations, associated to hereditary leiomy- omatosis and renal cell carcinoma (HLRCC) syndrome. Conclusion: It is essential to recognize the prototypical morphol- ogy of FH-deficient neoplasms, in order to avoid overdiagnosis of malignancy in uterine smooth muscle tumours, with special impact on young women who desire to preserve fertility. Although close follow- up is recommended, the majority of STUMPs have benign behav- iour. FH-deficient neoplasms may occur sporadically or associated to HLRCC syndrome, hence the importance of its prompt recognition to enable the early detection of aggressive forms of renal cell carcinoma. S114