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Background. Homologous recombination deficiency (HRD) is a valuable molecular marker for predicting response to platinum agents and poly(ADP-ribose)-polymerase (PARP) inhibitors. Germline and somatic alterations in the BRCA1 and BRCA2 genes are the major cause of HRD in ovarian cancer. However, in some cases, tumors arising in carriers of BRCA1 or BRCA2 pathogenic variants do not lose the normal copy of the corresponding gene and are not deficient for homologous recombination. Aim of the study was to present a case of high-grade ovarian carcinoma without HRD phenotype developed in a BRCA2 mutation carrier. Case report. A 48-year-old woman was diagnosed with multiple primaries: HER2-positive high-grade ovarian cancer and colorectal adenocarcinoma. analysis of the coding BRCA1/BRCA2 sequences revealed the germline BRCA2 c.658_659delgt [rs80359604] pathogenic variant. Given the unusual histological features, namely the absence of serous or endometrioid markers and high HER2 expression, we performed additional molecular analysis of the metastatic lesions in the lymph nodes. In all samples, the pattern of chromosomal instability did not match the HRD profile and there was loss of the mutant copy of the BRCA2 gene. Therefore, this tumor lacked the BRCAness phenotype. Conclusion. Tumors arising in HRR gene mutation carriers require additional molecular analysis for a comprehensive assessment of HRD.

Background. Lymphogenous metastasis in Ewing sarcoma is a relatively rare and poorly studied event associated with aggressive clinical course and poor prognosis. Until now, no risk factors for lymphogenous metastasis in patients with Ewing sarcoma are reported.The purpose of the study was to evaluate tumor characteristics as predictors for lymphogenous metastasis and to create a mathematical model for assessing the risk of developing lymph node metastases in patients with Ewing sarcoma.Material and Methods. Clinical characteristics of the tumor were studied in 88 patients with Ewing sarcoma: in 8 patients with lymphogenous metastasis and in 80 patients having no lymphogenous metastasis. The primary tumor in all patients with lymphogenous metastasis was found to have an extraskeletal origin. Morphological and immunohistochemical characteristics of the tumor were studied in 31 patients with Ewing sarcoma: in 8 patients with lymphogenous metastasis and in 23 patients without lymphogenous metastasis.Results. Statistical analysis and comparative evaluation of the characteristics of the immunophenotype and histological pattern of the tumor in the two studied groups showed significant differences regarding several of them: the structure of nuclear crowding (fusion of nuclei), focal hemorrhages, nuclear normochromasia, and positive expression of cytokeratins by tumor cells. The above signs (except for nuclear normochromasia) were the basis for creating a mathematical model capable of predicting the risk of lymphogenous metastases in Ewing sarcoma.Conclusion. The revealed association with lymphogenous metastasis of cytokeratin expression can be considered as indirect confirmation of the pathogenetic significance of the mesenchymal-epithelial transition in the mechanism of lymphogenous metastasis.