Breast cancer is the most commonly occurring malignancy and the leading cause of cancer-related death in women. Triple-negative breast cancer (TNBC) is the most aggressive subtype and is associated with high recurrence rates, high incidence of distant metastases, and poor overall survival. The aim of this study was to investigate the PI3K/PTEN/Akt/mTOR pathway as one of the most frequently deregulated pathways in cancer. We aimed to explore the impact of PI3K and mTOR oncogenes as well as the PTEN tumor suppressor on TNBC clinical behavior, prognosis, and multidrug resistance (MDR), using immunohistochemistry and copy number analysis by quantitative real-time PCR. Our results revealed that loss of PTEN and high expression of PI3K and mTOR proteins are associated with poor outcome of TNBC patients. PTEN deletions appeared as a major cause of reduced or absent PTEN expression in TNBC. Importantly, homozygous deletions of PTEN (and not hemizygous deletions) are a potential molecular marker of metastasis formation and good predictors of TNBC outcome. In conclusion, we believe that concurrent examination of PTEN/PI3K/mTOR protein expression may be more useful in predicting TNBC clinical course than the analysis of single protein expression. Specifically, our results showed that PTEN-reduced/PI3K-high/mTOR-high expression constitutes a ‘high risk’ profile of TNBC.

Nephrotic syndrome (NS) is characterized by proteinuria, hypoalbuminemia, edema, and hyperlipidemia. Apart from the traditional causes of NS, such as minimal change disease, focal segmental glomerulosclerosis, diabetes, infections, malignancies, autoimmune conditions, and nephrotoxic agents, there are also rare causes of NS, whose knowledge is of the utmost importance. The aim of this article was to highlight the less well-known causes that have a significant impact on diagnosis and treatment. Genetic syndromes such as Schimke immuno-osseous dysplasia, familial lecithin-cholesterol acyltransferase deficiency with two clinical variants (fish-eye Disease and the p.Leu364Pro mutation), lead to NS through mechanisms involving podocyte and lipid metabolism dysfunction. Congenital disorders of glycosylation and Nail–Patella Syndrome emphasize the role of deranged protein processing and transcriptional regulation in glomerular injury. The link of NS with type 1 diabetes, though rare, suggests an etiology on the basis of common HLA loci and immune dysregulation. Histopathological analysis, particularly electron microscopy, shows mainly podocyte damage, mesangial sclerosis, and alteration of the basement membrane, which aids in differentiating rare forms. Prompt recognition of these novel etiologies by genetic analysis, renal biopsy, and an interdisciplinary panel is essential to avoid delays in diagnosis and tailored treatment.

Introduction: Mammoplasty is a surgical procedure of placement of breast implants for aesthetic reasons or due to breast reconstruction after mastectomy for cancer. As the implant represents a foreign body, there is an inflammatory reaction and complications (most often capsule contractures, most rarely anaplastic large cell lymphoma), with different histopathological presentations (synovial metaplasia, chronic inflammation, dystrophic calcifications, granulomas around a foreign body type). Clinically, these complications are presented as tumor-like changes. Aim: The aim of the paper is to show the most significant histopathological parameters, age of the patients at the time of the complications, period that passed from the placement of the implant to the onset of complications and the existence of previous cancer. Material and methods: This study included patients with breast implants in the period of January 2019 to December 2023. Evaluating data from medical records, a retrospective study was performed, which included age of the patient at the time of complications, reasons for performing mammoplasty and the period that passed from mammoplasty to the appearance of complications. Archived material was used (paraffin molds and histopathological material stained with the hematoxylin-eosin method, as well as immunochistochemical stainings). Descriptive statistics methods (Fisher’s exact probability test) were used for data analysis. Results: Average age of the patients was 50.1 years, and the period that passed from the placement of the implant to the appearence of complications was 16.7 years. The breast cancer rate previously was 22%. Most common histopathological parameters were synovial metaplasia (100%) followed by chronic inflammation (76%), foreign material (52%) and granuloma around a foreign body (32%). The breast surgery was performed for cosmetic reasons in 88% of the patients. Conclusion: This study proved that the patients were older and that more time passed before complications occurred than was shown in literature. A large percentage of patients had the procedure only due to cosmetic reasons.

Ductal carcinoma in situ (DCIS) and atypical ductal hyperplasia (ADH) can precede invasive breast cancer. Early detection and differential diagnosis of these lesions improves prognosis. Usual ductal hyperplasia (UDH) has low malignant potential. There differential diagnosis is crucial. The aim was to analyze the gender and age of patients, differences in the histopathological and immunohistochemical presentation of UDH, ADH, and DCIS. This retrospective study included archived biopsy samples of 52 patients analyzed at the Institute of Pathology. Data on patient gender and age were obtained from medical records. H/E slides, and immunohistochemical markers (ER, PR, HER2, Ki-67, CK5/6) were used. Data was analyzed using descriptive statistical methods. Average age was 64.1 years. Out of the 52 patients, 49 were female, and 3 were male. The most common finding was DCIS. Isolated DCIS was found in 17% of patients, while 69% had DCIS associated with invasive carcinoma. ADH was isolated in 7% of patients, while 2% had ADH associated with DCIS and invasive carcinoma. UDH was present in 2% of patients. One male patient had UDH, while the other two had DCIS. Among women, the most common finding was DCIS associated with invasive carcinoma. ER was positive in 71.15% of cases and negative in 28.8%. PR was positive in 53.8% and negative in 46.2%. HER2 was positive in 38.4% and negative in 61.6%. Triple-negative status was observed in 5.76% of cases. All patients with UDH were positive for the CK5/6 marker, which was absent in ADH and DCIS. This study highlights the importance of early diagnosis while immunohistochemistry, especially CK5/6 and ER markers, plays a critical role.

Breast cancer is the most frequent and lethal type of cancer that affects women worldwide. Triple-negative breast cancer (TNBC) is the most aggressive type of breast cancer, having high rate of recurrence, metastasis, and mortality, with very limited options for treatment, and a tendency to develop resistance to conventional therapy. These circumstances mean that it is necessary to develop effective therapies for TNBC patients which would circumvent resistance mechanisms. The PAM and Wnt signaling pathways are among those responsible for therapy resistance in TNBC, as they also have major roles in different cellular processes such as metabolism, proliferation, metastasis, stemness, and survival. We analysed the expression of GSK3β and S6K1 as interacting components of the two pathways in order to examine the relation between them and determine whether they could be used as predictive markers in TNBC. The expression of mRNA was examined with real-time PCR and protein expression with immunohistochemistry. Our results showed that protein expression is in line with mRNA expression. We found a positive correlation between the mRNA expressions of GSK3β and S6K1, showing their coordinated transcription. We also showed that their simultaneous low expression is unfavorable for TNBC patients and could possibly be used as a predictive marker.