Freitas Ana Julia Aguiar de, Causin Rhafaela Lima, Calfa Stéphanie, Santana Iara Viana Vidigal, Balie Mariana, Hirai Welinton, Laus Ana Carolina, Araujo Hadson Silva, Hidalgo Filho Cassio Murilo, de Oliveira Bombarda Fernanda, da Silva Vinicius Duval, Evangelista Adriane Feijó, de Pádua Souza Cristiano, Reis Rui Manuel, Marques Márcia Maria Chiquitelli
Barretos Cancer Hospital, Molecular Oncology Research Center, Teaching and Research Institute, Barretos, 14784-400, Brazil.
Barretos Cancer Hospital, Barretos, 14784-400, Brazil.
Breast Cancer Res Treat. 2025 May 28. doi: 10.1007/s10549-025-07718-2.
Breast cancer remains a major global health concern due to its high incidence and mortality among women. Accurate prognostic stratification is essential for guiding treatment and improving outcomes. The Nottingham grading system evaluates tumor differentiation based on architectural features, nuclear atypia, and mitotic activity, serving as a key tool in assessing breast cancer prognosis.
To investigate gene expression patterns associated with histological grades and immunohistochemical subtypes of breast cancer, and to explore their relationship with clinical outcomes, including recurrence, overall survival (OS), and disease-free survival (DFS).
In a cohort of 82 breast cancer patients, gene expression profiling was performed using the nCounter® Breast Cancer 360™ panel. Tumors were classified according to the Nottingham grading system. Differential gene expression analysis was conducted across histological grades and subtypes, with subsequent correlation to clinical outcomes.
Nearly half of the patients exhibited histological grade 3 tumors. Six genes-BIRC5, CDC6, FOXM1, TOP2A, MYBL2, and UBE2C-were significantly overexpressed in high-grade tumors. These genes are involved in key cell cycle regulatory pathways. Their overexpression was significantly associated with higher rates of disease recurrence and poorer OS and DFS, highlighting their prognostic value.
This study reinforces the prognostic utility of histological grading and reveals a set of cell cycle-related genes whose overexpression is linked to adverse outcomes in breast cancer. These findings suggest potential biomarkers for risk stratification and therapeutic targeting, offering insights for personalized management of patients beyond traditional histological assessments.
由于乳腺癌在女性中的高发病率和高死亡率，它仍然是全球主要的健康问题。准确的预后分层对于指导治疗和改善治疗结果至关重要。诺丁汉分级系统根据组织结构特征、核异型性和有丝分裂活性评估肿瘤分化程度，是评估乳腺癌预后的关键工具。
研究与乳腺癌组织学分级和免疫组化亚型相关的基因表达模式，并探讨它们与临床结局（包括复发、总生存期（OS）和无病生存期（DFS））的关系。
在一组82例乳腺癌患者中，使用nCounter®乳腺癌360™检测板进行基因表达谱分析。根据诺丁汉分级系统对肿瘤进行分类。对不同组织学分级和亚型进行差异基因表达分析，随后将其与临床结局相关联。
近一半的患者表现为组织学3级肿瘤。六个基因——BIRC5、CDC\alpha、FOXM1、TOP2A、MYBL2和UBE2C——在高级别肿瘤中显著过表达。这些基因参与关键的细胞周期调控途径。它们的过表达与更高的疾病复发率以及更差的总生存期和无病生存期显著相关，突出了它们的预后价值。
本研究强化了组织学分级的预后效用，并揭示了一组与细胞周期相关的基因，其过表达与乳腺癌的不良结局相关。这些发现提示了潜在的风险分层生物标志物和治疗靶点，为超越传统组织学评估的患者个性化管理提供了思路。
