Tumor-infiltrating lymphocytes (TILs) are pivotal in the immune response against breast cancer (BC), with their prognostic and predictive significance varying across BC subtypes. In triple-negative BC (TNBC), higher TIL levels correlate with improved prognosis and treatment response, guiding therapeutic strategies and potentially offering avenues for treatment de-escalation. In metastatic TNBC, TILs identify patients with enhanced immunotherapy response. HER2+ BC, similar to TNBC, exhibits positive correlations between TILs and treatment response, especially in neoadjuvant settings. Luminal BC generally has low TILs, with limited prognostic impact. Single hormone receptor-positive BCs show distinct TIL associations, emphasizing subtype-specific considerations. TILs in ductal carcinoma in situ (DCIS) display ambiguous prognostic significance, necessitating further investigation. Standardizing TIL assessment methods is crucial for unlocking their full potential as biomarkers, guiding treatment decisions, and enhancing patient care in BC.

Oral squamous cell carcinoma (OSCC) remains a significant global health challenge, representing 90% of oral malignancies. Despite therapeutic advances, patient outcomes remain poor, highlighting the need for novel prognostic biomarkers and treatment targets. We investigated the expression patterns of NTRK genes and their corresponding proteins (TrkA, TrkB, and TrkC) in OSCC, analyzing their relationships with clinical outcomes and potential as therapeutic targets. We examined 93 OSCC tissue samples using immunohistochemistry and quantitative real-time PCR. Protein expression was quantified using the H-score method. We analyzed correlations between Trk expression, clinicopathological parameters, and 2-year survival rates using chi-square tests, Mann–Whitney U tests, and Kaplan–Meier survival analysis. TrkA showed near-universal expression (97.8%—91 patients) in OSCC samples, with high expression levels significantly correlating with lower tumor grade (p = 0.014) and improved 2-year survival (p = 0.011). While TrkB and TrkC were expressed in 65.5% and 84.9% of cases, respectively, neither showed significant associations with clinical parameters. NTRK2 and NTRK3 mRNA levels demonstrated a strong positive correlation (R = 0.64, p = 0.002), suggesting coordinated regulation. Our findings establish TrkA as a promising positive prognostic marker in OSCC, warranting investigation as a therapeutic target. The strong correlation between NTRK2 and NTRK3 expression suggests shared regulatory mechanisms in OSCC pathogenesis. Further studies with larger cohorts and longer follow-up periods are needed to validate these findings and explore their therapeutic implications.

Background/Objectives: We focused on the expression of a novel immune marker, cytoplasmic stimulator of interferon genes (STING), in the cohort of primary renal cell cancer (RCC) with venous tumor thrombus (VTT), in conjunction with the assessment of tumor-infiltrating leucocytes (TILs). Methods: The study group comprised 82 patients with clear cell RCC and VTT, operated on in the years 2012–2019 in two university urological centers. Tissue microarrays were constructed, and respective antibodies were used for staining purposes. The biomarkers were analyzed in primary RCC and VTT. Results: The frequency of STING expression in both analyzed compartments was similar (p = 0.18). Its presence correlated with no clinicopathological features but for necrosis in VTT only (p = 0.0023). PD-L1 expression in the primary tumor was associated with STING in tumor cells in the same compartment (p = 0.02). On the contrary, VISTA expression was correlated with the presence of STING in VTT. TIL presence was associated with positive PD-L1 (p = 0.008) and STING (p < 0.05) expression in the primary tumor. Strong STING expression in VTT was associated with inferior overall survival (OS) (p = 0.0061). TIL presence emerged as a robust prognostic factor for OS in both primary tumor (p = 0.021) and VTT (p = 0.034). Conclusions: We presented for the first time the prognostic values of STING in a contemporary cohort of RCC patients with VTT. STING expression in VTT showed prognostic potential, while TIL assessment proved to be a particularly valuable prognostic tool that can be readily implemented in routine pathological evaluation.

Introduction: This study aimed to evaluate the impact of tumour-infiltrating lymphocytes (TILs) on the expression of immune-related genes and prognosis in single hormone receptor-positive breast cancer. Material and methods: Tumour-infiltrating lymphocytes were analysed according to the...

Primary breast neuroendocrine tumors (BNETs) are rare malignancies recently redefined by the World Health Organization (WHO) 2019 classification, which mandates neuroendocrine morphology in over 90% of tumor cells. This systematic review aims to provide the first comprehensive analysis of BNETs strictly adhering to these diagnostic criteria. A systematic search of PubMed and Embase was conducted for studies published between January 2019 and February 2025. Eligible studies included adult patients with primary BNETs diagnosed per WHO 2019 criteria, reporting clinical, pathological, or treatment data. Eight studies met inclusion criteria, encompassing 203 patients. BNETs predominantly affected postmenopausal women and typically presented as early-stage, hormone receptor-positive tumors. Estrogen receptor positivity was nearly universal (75.8%-100%), while HER2 overexpression was rare. Most tumors were grade 2 with low to moderate Ki-67 indices, and disease-free survival (DFS) rates were favorable (1-year DFS: 98.6%; 5-year DFS: 91.1%). Molecular studies suggested distinct genomic profiles compared to invasive breast carcinoma of no special type (IBC-NST), including lower TP53 and PIK3CA mutation rates and higher frequency of KMT2C and FOXA1 alterations. Somatostatin receptor 2 A (SSTR2A) expression was observed in up to 71% of cases in earlier studies, supporting potential for somatostatin analog therapy, although data were based on tumors not meeting current criteria. BNETs represent a biologically distinct subset of breast cancers with favorable prognostic features and a consistent luminal-like phenotype. However, evidence on optimal treatment remains limited. Further large-scale, prospective studies are needed to define clinical management and validate molecular findings.

Background/Objectives: Gastric cancer (GC) remains a major cause of cancer-related deaths worldwide. The tumor microenvironment, particularly tumor-associated macrophages (TAMs), plays a key role in tumor progression and angiogenesis. M2-polarized TAMs are considered pro-tumorigenic; however, their prognostic significance and relationship with microvessel density (MVD) at the invasive front of GC remain unclear. This study evaluated the prognostic significance of CD163⁺ M2 TAMs and MVD at the invasive front of gastric adenocarcinoma. Methods: A retrospective analysis was performed on 106 patients who underwent radical R0 surgery for GC without neoadjuvant therapy. Immunohistochemistry using CD163 and CD34 antibodies was applied to quantify M2 TAMs and MVD at the invasive front. Median values were used as cut-offs. Associations with clinicopathological features were analyzed, and survival was assessed using Kaplan–Meier and Cox regression models. Results: The mean number of CD163⁺ M2 TAMs was 70, and the mean MVD was 33. A significant positive correlation between M2 TAMs and MVD was observed (p = 0.001). Higher M2 TAMs infiltration was associated with deeper tumor invasion (pT) and showed a trend toward advanced pTNM stage. In univariate analysis, neither M2 TAMs nor MVD was associated with survival. Multivariate analysis identified pT (p = 0.02) and MVD (p = 0.03) as independent prognostic factors, with increased MVD associated with improved overall survival. Conclusions: CD163⁺ M2 TAMs are linked to angiogenesis at the invasive front of gastric cancer and correlate with tumor invasiveness. Increased MVD may represent an independent favorable prognostic marker, highlighting the biological importance of the invasive tumor front.