Triple-negative breast cancer (TNBC) is the most aggressive breast cancer subtype and is associated with high recurrence rates, a high incidence of distant metastases and poor overall survival. The aim of this study was to investigate the role of PD-L1, EGFR and AR expression in TNBC promotion and progression. To that end, we analyzed the immunohistochemical expression of these genes in 125 TNBC patients and their relation to clinicopathological parameters and survival. An elevated expression of PD-L1 was significantly correlated with higher tumor and nuclear grade, while a low expression was correlated with loco-regional recurrence without any influence on survival. Contrary to this, the expression of AR showed a positive impact on the DFI and a negative association with tumor grade. Furthermore, PD-L1 and AR demonstrated simultaneous expression, and further co-expression analysis revealed that a positive expression of PD-L1/AR notably correlates with tumor and nuclear grade and has a significant impact on a longer DFI and OS, while a negative PD-L1/AR expression is significantly associated with metastases. Therefore, our results suggest that positive PD-L1/AR expression is beneficial for TNBC patients. In addition, an elevated expression of EGFR contributes to metastases and a worse DFI and OS. In conclusion, we think that low PD-L1/low AR/high EGFR expression followed by high Ki67 expression constitutes a ‘high risk’ profile of TNBC.

Malignant gliomas are the most common primary tumors of the central nervous system (CNS), originating from glial cells. They account for 30% of all CNS tumors. Among them, glioblastoma (GBM) is the most common, accounting for 45% of all glial tumors, while low-grade gliomas (LGGs) account for 31.8% of all gliomas. The aim of this study was to analyze the protein-expression profile of HTR4 and PDE4D genes in patients with glioma by immunohistochemical (IHC) analysis, to determine whether some interrelationship between them exists, to correlate their expression with clinical and histopathological parameters and therapy, and to determine their impact on patients’ survival. In addition, we analyzed the level of genomic instability (GI) (microsatellite (MIN), chromosomal (CIN) and total GI) by AP-PCR, in order to understand whether it can represent a tool for biological stratification of glioma tumors and risk assessment. Our results revealed that synchronized expression of 5-HTR4 and PDE4D proteins represents a stable modulatory signaling axis of glial-tumor biology, and reflects the activity of cAMP signaling pathway, but cannot independently stratify patients. Moreover, our study confirms that the combination of MIN, CIN and total GI represents a powerful tool for biological tumor stratification, risk assessment and understanding the pathobiological spectrum of the disease.

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.

Glial brain tumours, including astrocytoma IDH (Isocitrate Dehydrogenase) mutant and glioblastoma IDH wild-type, are highly malignant brain tumours with poor clinical outcomes. Genomic instability, encompassing microsatellite (MIN) and chromosomal instability (CIN), drives tumour heterogeneity and evolution. In this study, genomic instability was analysed in 85 patients using AP-PCR (Arbitrarily Primed Polymerase Chain Reaction) by comparing tumour and normal tissue (blood) DNA profiles of the same patient. Both types of alterations were present in all analysed samples, contributing almost equally to the total level of genomic instability. The dominant pattern of genomic instability in our cohort was low overall instability, predominantly manifesting as low-degree microsatellite instability. A general decrease in genomic instability was observed with increasing tumour grade. Glioblastoma IDH wild-type was more prevalent in older patients, whereas astrocytoma IDH mutant predominated in younger individuals. Notably, low genomic instability (both MIN and CIN) was associated with poorer survival in patients over 50 years of age. Females, compared to males, exhibited higher MIN in grade 2 tumours and elevated CIN in grade 4 tumours. Our results confirm that genomic instability contributes to tumour progression, MIN being the pivotal factor, and could serve as a prognostic biomarker in malignant gliomas.