RESUMO
Trop-2, a transmembrane glycoprotein, has been identified in human epithelial cells as a contributor to tumor growth and unfavorable prognosis in breast cancer (BC). Our study aimed to assess the expression of Trop-2 protein via immunohistochemistry (IHC) and correlate it with clinicopathological features in early luminal-like BC. We conducted a cross-sectional study evaluating Trop-2 protein expression in tissue microarrays using IHC. The expression was evaluated by the H-score and the following categorization was used: H-Score 0 to <100 as low, H-Score 100 to 200 as intermediate, and H-Score >200 to 300 as high. The study included 84 patients with a median age of 57, of whom 70% had invasive ductal carcinomas, 75% were classified as T2, and 47.6% had no affected lymph nodes. Trop-2 expression was high in 56% of patients and intermediate in 38%. None of the patients had an H-Score of zero. No correlation was observed between Trop-2 expression and clinicopathological features, including age, histological subtype, grade, Ki67, tumor size, nodal status, lymphovascular invasion, tumor subtype, and pathological staging. We demonstrated that Trop-2 is highly expressed in early luminal-like BC and is not influenced by clinicopathological features.
Assuntos
Neoplasias da Mama , Feminino , Humanos , Biomarcadores Tumorais , Neoplasias da Mama/patologia , Estudos Transversais , Linfonodos/metabolismo , Metástase Linfática , Prognóstico , Receptor ErbB-2/metabolismo , Receptores de ProgesteronaRESUMO
Prognostic and predictive factors for early and late distant distance recurrence risk in estrogen-receptor positive and HER2-receptor negative early breast cancer are well known, but not all these variables work equally for the prediction. The following are the most widely accepted variables for categorizing risk levels: clinic-pathologic features (tumor size, lymph node involvement, histological grade, age, menopausal status, Ki-67 expression, estrogen, and progesterone expression), primary systemic treatment response (pathologic response and/or Ki-67 downstaging), and gene expression signatures stratification. Treatment guidelines from cancer societies and collaborative groups, online predict-tools, real-world data and experts' opinion recommends different adjuvant strategies (chemotherapy, endocrine therapy, ovarian suppression, olaparib, or abemaciclib) depending on the low (< 10%), intermediate (10%-20%) or high-risk of distance recurrence at least in the first 5 years. Multiple randomized prospective trials were updated in 2022, that evidence allow us to perform a stratification of risk in pre- and postmenopausal women with estrogen-receptor positive and HER2-receptor negative early breast cancer based on a combination of clinic-pathologic features and genomic assays and guide the adjuvant systemic treatment recommendation for those with high risk.
RESUMO
This study aimed to evaluate in vitro the possible mechanisms underlying the estrogenic potential of benzalkonium chloride (BAC) as a disinfectant emerging contaminant. Effects of BAC at the environmentally-relevant concentrations on estrogen synthesis and estrogen receptor (ER) signaling were assessed using the H295R steroidogenesis assay and the MCF-7 proliferation assay, respectively. Results showed that exposure to BAC at concentrations of 1.0-1.5 mg/L for 48 h significantly increased estradiol production of H295R cells in a concentration-dependent manner. Transcription of steroidogenic genes 3β‐HSD2, 17β‐HSD1, 17β‐HSD4, and CYP19A were significantly enhanced by BAC. In ER-positive MCF-7 cells, exposure to 0.5-1.5 mg/L BAC for 48 h significantly promoted cell proliferation and increased the expressions of ERα and G-protein coupled estrogen receptor 1. Flow cytometry analysis showed that 0.5-1.5 mg/L BAC significantly decreased the percentage of cells in G0/G1 phase, increased the percentage in S phase, and BAC at concentrations of 1.0 and 1.5 mg/L increased the G2/M phase cells. Findings of the study suggested that BAC at environmentally-relevant concentrations might act as a xenoestrogen through its inhibitory effect on steroidogenesis and ER-mediated mechanism.