This study was targeted on a metabolomic approach to compare the blood serum free amino acid profiles and concentration of confirmed breast cancer (stages I–III) patients to healthy controls in order to establish reliable biomarkers of early detection and prediction of breast cancer. The ultra-high-performance liquid chromatography coupled with mass spectrometry using positive ionization electrospray was applied for the picoline-derivatized serum free amino acids using the EZ:faastTM kit. Multivariate statistical analysis principal component analysis, partial least squares discrimination analysis and univariate analysis were applied in order to discriminate between patient groups and putative amino acid biomarkers for breast cancer. A significant decrease of amino acid concentrations between the breast cancer group and the control group was positively correlated with breast cancer progression. Arginine, Alanine, Isoleucine, Tyrosine and Tryptophan were identified as being good potential discriminants (AUROC ≥0.85) and suitable candidates to diagnose and predict the breast cancer progression.

Aim. Multigene panel testing for Hereditary Breast and Ovarian Cancer (HBOC) using next generation sequencing is becoming more common in medical care.We report our experience regarding deleterious mutations of high and moderate-risk breast cancer genes (BRCA1/2, TP53, STK11, CDH1, PTEN, PALB2, CHEK2, ATM), as well as more recently identified cancer genes, many of which have increased risk but less well-defined penetrance.Methods. Genetic testing was performed in 130 consecutive cases with breast cancer referred to our clinic for surgical evaluation and who met the 2016 National Comprehensive Cancer Network (NCCN) criteria for genetic testing.Results. 82 patients had pathogenic/likely pathogenic mutations and VUS mutations, and 48 were negative; 36 of the pathogenic mutations were in the high-risk genes and 16 were in the moderate risk genes and only 5 cases in the intermediary risk group.From the VUS mutation group 21 cases were in the intermediary risk group, 9 cases were in the moderate risk group and only 7 cases in high risk group.The most frequent BRCA1 variant was c.3607C>T (7 cases) followed by c.5266dupC and c.4035delA (each in 4 cases). Regarding BRCA-2 mutations we identified c.9371A>T and c.8755-1G>A in 6 cases and we diagnosed VUS mutations in 3 cases.Conclusion. Our study identified 2 mutations in the BRCA1 gene that are less common in the Romanian population, c.3607C>T and c.4035delA. Both variants had particular molecular phenotypes, c.3607C>T variant respecting the triple negative pattern of BRCA1 breast cancer while c.4035delA were Luminal B HER positive.

The purpose of this study is to evaluate the relationship between the pathogenic/likely pathogenic mutations, US features, and histopathologic findings of breast cancer in mutation carriers compared to non-carrier patients. Methods: In this retrospective study, we identified 264 patients with breast cancer and multigene panel testing admitted to our clinic from January 2018 to December 2020. Patient data US findings, US assessment of the axilla, multigene panel tests, histopathology, and immunochemistry reports were reviewed according to the BI-RADS lexicon. Results: The study population was comprised of 40% pathogenic mutation carriers (BRCA1, BRCA2, CHEK2, ATM, PALB, TP 53, NBN, MSH, BRIP 1 genes) and 60% mutation-negative patients. The mean patient age was 43.5 years in the carrier group and 44 years in the negative group. Carrier patients developed breast cancer with benign morphology (acoustic enhancement, soft elastography appearance) compared to non-carriers (p < 0.05). A tendency towards specific US features was observed for each mutation. BRCA1 carriers were associated with BC with microlobulated margins, hyperechoic rim, and soft elastography appearance (p < 0.05). Estrogen receptor (ER)-negative tumors were associated with BRCA1, TP53, and RAD mutations, while BRCA2 and CHEK2 were associated with ER-positive tumors. Conclusions: Patients with pathogenic mutations may exhibit BC with benign US features compared to negative, non-carrier patients. BRCA1, TP53, and RAD carriers account for up to one third of the ER tumors from the carrier group. Axillary US performed worse in depicting involved lymph nodes in carrier patients, compared to negative patients.

Background/Objectives: Infertility is a reproductive disorder affecting approximately 10–15% of reproductive-age couples worldwide. Recent studies have suggested that miRNAs in follicular fluid may provide insights into reproductive potential and follicle health. This study evaluated the altered profile of miRNAs in the follicular fluid in patients undergoing IVF, considering the underlying etiology of infertility. Among our study participants, we identified four major underlying causes of infertility: polycystic ovary syndrome (PCOS), pelvic inflammatory disease (PID), male factor infertility, and unexplained infertility (UI). Methods: This study aimed to assess whether these infertility diagnoses are associated with distinct follicular behaviors and to identify altered miRNA patterns linked to these conditions. Ingenuity Pathway Analysis (IPA) was used to evaluate the impact of the altered miRNA signature on key biological processes. Results: The bioinformatics analysis of microarray data revealed altered miRNA patterns in FF for selected subgroups. Compared to healthy controls, 25 differentially expressed miRNAs were identified in PCOS (9 downregulated and 16 overexpressed), 21 in PID (15 downregulated and 6 overexpressed), and 34 in UI (24 downregulated and 10 overexpressed). These altered miRNA signatures indicate a complex interplay with essential signaling pathways, including hormonal regulation and tissue remodeling. Conclusions: Our analysis revealed key miRNAs that were differentially expressed across selected groups, indicating their potential as biomarkers for more accurate diagnosis and targeted treatment strategies. These findings provide valuable insights into the molecular mechanisms underlying reproductive disorders and underscore the importance of further research to develop targeted interventions that can enhance patient outcomes.

Introduction: Breast cancer is the most common cancer in women worldwide, and Romania makes no exception from this trend. Genetic screening for Hereditary Breast and Ovarian Cancer began to be used on a larger scale after the introduction of Next Generation Sequencing. The aim of this study was to assess the association of deleterious mutations responsible for breast cancer with histopathological and immunohistochemical prognostic factors and to identify some genetic variants in the BRCA1 and BRCA2 genes. Method: 80 patients with breast cancer and negative genetic test or pathogenic variants on BRCA1/2, TP53, PALB2, CHEK2, ATM genes were included. All the cases had a prior histological diagnosis and complete immunohistochemical features. The genetic testing was conducted through a multigene panel. Results: 65% of patients had a deleterious mutation on BRCA genes. In 97.5% of cases the histology was invasive ductal carcinoma. Significant differences were identified between BRCA1 group and negative mutation group regarding estrogen receptor (ER) (p=0.0051), progesterone receptor (PR) (p=0.0004) and Ki67 (p=0.001). Seven breast cancer patients had BRCA1 c.3607C>T variant, which was statistically significantly associated with triple- negative breast cancer (p A variant in 3 cases and the c.9371A>T variant in 3 cases. Discussion and conclusion: Our study confirmed the association of BRCA1 mutations with negative ER, PR or triple negative breast cancer (TNBC). Description of BRCA1 c.3607C>T mutation for the first time in Romanian population and its association with TNBC will need further investigation.

Background and clinical significance: Ectopic ureters are a rare urinary tract malformation, typically diagnosed in childhood and infrequently in adulthood. The prenatal detection by ultrasound and magnetic resonance imaging (MRI) of this clinical entity has scarcely been reported. Careful foetal scanning during the late second and third trimester might provide clues and lead to prenatal detection. However, even the postnatal diagnosis is challenging, and often delayed towards adulthood, since the condition may present with nonspecific symptoms, leading to underdiagnosis or misdiagnosis. In female patients, approximately 25% of ectopic ureters open into the vagina. Due to the high risk of recurrent urinary tract infections and the potential development of uretero-hydronephrosis, timely diagnosis is essential, and prompt surgical correction is mandated. Case presentation: We report the case of a 33-year-old GII PI patient diagnosed with cystic dysplasia of the left foetal kidney at the 16 WG (weeks of gestation) scan. The malformation was consistent at 21 WG when karyotyping by amniocentesis identified a normal female molecular karyotype. MRI performed at 28 weeks confirmed the left renal dysplasia and raised the suspicion of an abnormal insertion of the left ureter into the vagina. After delivery, the vaginal ureteral ectopy was confirmed at 3 weeks postpartum via cystoscopy. Postpartum whole exome sequencing identified a variant of uncertain significance (VUS) mutation in the SOX 13 gene (SRY-box transcription factor 13). Renal scintigraphy performed 7 months postnatally identified a hypo/afunctional left kidney which led to the indication of nephrectomy by the paediatric urologist. The surgical intervention was performed at 8 months postpartum with a favourable outcome. Conclusions: Ectopic ureters are a pathology generating life-long morbidity and discomfort of the offspring and young adult. Awareness to this pathology must be raised among clinicians, especially regarding the potential detection by minute prenatal ultrasound examinations, followed by MRI to refine diagnosis. Postnatally, the persistence of suspicious yet unspecific symptoms, in both males and females, must trigger thorough imaging/cystoscopic examination to reach diagnosis and provide correct management.