Evaluation of Prostate-Specific Membrane Antigen (PSMA) Immunohistochemical Expression in Early-Stage Breast Cancer Subtypes.

Breast cancer, known for its diverse subtypes, ranks as one of the leading causes of cancer-related deaths. Prostate-specific membrane antigen (PSMA), primarily associated with prostate cancer, has also been identified in breast cancer, though its role remains unclear. This study aimed to evaluate PSMA expression across different subtypes of early-stage breast cancer and investigate its correlation with clinicopathological factors. This retrospective study included 98 breast cancer cases. PSMA expression was examined in both tumor cells and tumor-associated blood vessels. The analysis revealed PSMA expression in tumor-associated blood vessels in 88 cases and in tumor cells in 75 cases. Ki67 expression correlated positively with PSMA expression in blood vessels (p < 0.0001, RSpearman 0.42) and tumor cells (p = 0.010, RSpearman 0.26). The estrogen and progesterone receptor expression correlated negatively with PSMA levels in blood vessels (p = 0.0053, R Spearman -0.26 and p = 0.00026, R Spearman -0.347, respectively). Human epidermal growth factor receptor 2 (HER2) status did not significantly impact PSMA expression. We did not detect any statistically significant differences between breast cancer subtypes. These findings provide evidence for a heterogenous PSMA expression in breast cancer tissue and suggest its correlation with tumor aggressiveness. Despite the limited sample size, the study provides valuable insights into the potential of PSMA as a prognostic, diagnostic, and therapeutic target in the management of breast cancer.

Expression of semaphorin 3A (SEMA3A) in breast cancer subtypes.

Breast cancer is a major health concern, and its accurate diagnosis and management depend on identifying its histological type and biological subtype. Semaphorin-3A (SEMA3A) is a membrane protein with diverse roles in cellular processes, including cancer progression and angiogenesis regulation. However, its role in breast cancer remains poorly understood. This study aimed to evaluate SEMA3A expression in breast cancer and investigate its distribution across breast cancer subtypes: luminal A, luminal B, HER2-positive, and triple-negative breast cancer (TNBC). Immunohistochemical evaluation was performed on 98 breast cancer patients' tumor specimens, and SEMA3A expression was assessed in tumor cells and vessels. The study included the analysis of the Ki67 proliferation index, estrogen receptor (ER) expression, progesterone receptor (PR) expression, and HER2 status in conjunction with SEMA3A expression. Analysis indicated positive expression of SEMA3A in breast cancer cells in 60 out of 98 cases. SEMA3A expression correlated positively with Ki67 levels in tumor cells (p = 0.0005, R Spearman 0.338). Notably, a negative correlation was found between SEMA3A expression and ER and PR levels in tumor cells (p = 0.04, Spearman's R = - 0.21 and p = 0.016, Spearman's R = - 0.25 respectively). HER2 status did not significantly influence SEMA3A expression. The study demonstrated positive SEMA3A expression in tumor vessels across all subtypes in 91 out of 98 cases, suggesting its involvement in endothelial cell function. However, no significant differences in SEMA3A expression were observed between breast cancer subtypes either in vessels or tumor cells. These findings suggest that elevated SEMA3A expression may be associated with worse prognosis in breast cancer, especially in ER- and PR-negative tumors. Further investigations are warranted to fully comprehend the role of SEMA3A in breast cancer biology, which may lead to the identification of novel therapeutic targets and personalized treatment strategies for breast cancer patients.

Immunohistochemical Expression of the SERPINA3 Protein in Uterine Fibroids.

BACKGROUND: SERPINA3 (α-1-antichymotrypsin, AACT, ACT) is produced by the liver and released into plasma in an anti-inflammatory response and plays a role as a modulator of extracellular matrix (ECM) by inhibiting serine proteases. Numerous studies proved an increased level of SERPINA3 in many types of cancer, which could be linked to SERPINA3's anti-apoptotic function. AIM: In the context of progressive ECM fibrosis during the development of uterine fibroids, which are one of the most common hypertrophic changes within the uterus, it is interesting to describe the level of SERPINA3 protein in this type of lesion and the surrounding tissues. METHODS: We used immunohistochemical staining of the SERPINA3 protein and compared the intensity of the signal between the myoma tissue and the surrounding normal tissue. RESULTS: We showed a surprising reduction in the amount of the SERPINA3 protein within uterine fibroids compared to surrounding tissues. CONCLUSION: This observation sheds new light on the role of this protein in the formation of proliferative changes and suggests that understanding the mechanism of its action may become the basis for the development of new diagnostic and therapeutic tools.

Molecular alterations of driver genes in non-small cell lung cancer: from diagnostics to targeted therapy.

Lung cancer is the leading cause of cancer death all over the world. The majority (80-85 %) of lung cancer cases are classified as non-small cell lung cancer (NSCLC). Within NSCLC, adenocarcinoma (AC) and squamous cell carcinoma (SCC) are the most often recognized. The histological and immunohistochemical examination of NSCLC is a basic diagnostic tool, but insufficient for comprehensive therapeutic decisions. In some NSCLC patients, mainly adenocarcinoma, molecular alterations in driver genes, like EGFR, KRAS, HER2, ALK, MET, BRAF, RET, ROS1, and NTRK are recognized. The frequency of some of those changes is different depending on race, and between smokers and non-smokers. The molecular diagnostics of NSCLC using modern methods, like next-generation sequencing, is essential in estimating targeted, personalized therapy. In recent years, a breakthrough in understanding the importance of molecular studies for the precise treatment of NSCLC has been observed. Many new drugs were approved, including tyrosine kinase and immune checkpoint inhibitors. Clinical trials testing novel molecules like miRNAs and trials with CAR-T cells (chimeric antigen receptor - T cells) dedicated to NSCLC patients are ongoing.

Expression of E4 Protein and HPV Major Capsid Protein (L1) as A Novel Combination in Squamous Intraepithelial Lesions.

We aim to describe the relationship between the immunohistochemical expression patterns of HPV E4 markers and the presence of HPV major capsid protein (L1) in cervical tissues obtained by biopsy of patients with abnormal liquid-based cytology (LBC) results, HR HPV infections, or clinically suspicious cervix. A novel HPV-encoded marker, SILgrade-E4 (XR-E4-1), and an HPV (clone K1H8) antibody were used to demonstrate the expression in terminally differentiated epithelial cells with a productive HPV infection in the material. A semiquantitative analysis was performed based on light microscope images. The level of E4 protein decreased with the disease severity. Patients with LSIL-CIN 1 and HSIL-CIN 2 diagnoses had significantly lower levels of HPV major capsid protein (L1) than those without confirmed cervical lesions. Our analysis confirms a higher incidence of L1 in patients with molecularly diagnosed HPV infections and excluded lesions of LSIL-CIN 1 and HSIL-CIN 2. Further studies on the novel biomarkers might help assess the chances of the remission of lesions such as LSIL-CIN 1 and HSIL-CIN 2. Higher levels of E4 protein and L1 may confirm a greater probability of the remission of lesions and incidental infections. In the cytological verification or HPV-dependent screening model, testing for E4 protein and L1 expression may indicate a group with a lower risk of progression of histopathologically diagnosed lesions.

Immunohistochemical Expression of Vitamin D Receptor in Uterine Fibroids.

One of the many factors involved in the development of uterine fibroids is vitamin D deficiency. One aspect of this deficiency is decreased serum concentration of calcidiol-25(OH)D, a metabolite of D3 vitamin. The active form of vitamin D3, which arises after numerous enzymatic reactions, is calcitriol-1,25(OH)2D3; this compound is transported to various body tissues. Vitamin D possesses extra-genomic effects due to its influence on various signaling pathways, i.e., through activating tyrosine kinases and by genomic effects via binding to a specific nuclear receptor, vitamin D receptor (VDR). The vitamin D/VDR complex regulates the expression of genes and is involved in the pathogenesis of fibroids. Numerous studies have shown that vitamin D supplementation reduces fibroid size. It has also been shown that the expression of VDR in myoma tissue is significantly lower than in the uterine muscle tissue at the tumor periphery. However, the expression of VDR in non-myoma uterine muscle has not previously been investigated. Our VDR expression studies were performed immunohistochemically with tissue microarrays (TMA) in three tissue groups: 98 uterine myoma tissues, 98 uterine tissues (tumor margin), and 12 tissues of normal uterine muscle (i.e., without fibroids). A statistical analysis showed significantly lower VDR expression in uterine muscle at the periphery of the fibroid than in healthy uterine muscle. Lower expression of VDR at the periphery of the myoma compared to that in normal uterine muscle may indicate potential for new myomas. This observation and the described reduction in the size of fibroids after vitamin D supplementation supports the hypothesis of causal development of uterine fibroids and may be useful for the prevention of re-development in the event of their excision from the uterus.