Ebrahim Noura A A, Hussein Mustafa A, Sobeih Mohamed Emam, Amin Nancy H
Oncologic Pathology Department, National Cancer Institute (NCI) - Cairo University, Giza, Egypt.
Medical Oncology Department, National Cancer Institute (NCI) - Cairo University, Giza, Egypt.
BMC Cancer. 2025 Jun 5;25(1):1008. doi: 10.1186/s12885-025-14402-7.
Triple-negative breast cancer (TNBC) is characterized by its aggressive behavior and limited treatment options, primarily due to the lack of expression of estrogen receptor (ER), progesterone receptor (PR), and human epidermal growth factor receptor 2 (HER2). TROP-2, a transmembrane glycoprotein, exhibits notable overexpression in a spectrum of highly aggressive cancers including pancreatic, gastric, and ovarian cancers. This overexpression has established TROP-2 as a key prognostic biomarker and a promising target for therapeutic intervention.
This research examines the correlation between TROP-2 expression and clinicopathological features in TNBC, assessing its utility as both a prognostic indicator and a candidate for targeted precision therapy.
Retrospective analysis of 80 TNBC patient samples from January 2016 to December 2019 at the National Cancer Institute, Cairo University, Egypt was carried out. Formalin-fixed, paraffin-embedded (FFPE) tissues were evaluated for TROP-2 expression using immunohistochemistry. Clinical and pathological data including patient demographics, tumor characteristics, treatment modalities, and survival outcomes were gathered. TROP-2 expression was correlated with clinicopathological variables and survival metrics (overall survival, OS; disease-free survival, DFS).
A high expression of TROP-2 was observed in 78% of cases, exhibiting notable heterogeneity in intensity, proportion of positive cells, and H-score. TROP-2 expression correlated with larger tumor dimensions and advanced nodal involvement, suggesting its contribution to tumor aggressiveness. Elevated TROP-2 intensity and H-scores were significantly associated with poorer overall survival (OS; p = 0.003 and p = 0.007, respectively) and disease-free survival (DFS; p = 0.002 for both). Multivariate analysis revealed TROP-2 intensity, percentage of expression, and H-score as independent predictors of OS (p = 0.02, 0.001, and 0.012, respectively). Similarly, these variables were identified as independent prognostic indicators for DFS, with significant p-values of 0.002, 0.009, and 0.002.
Our research validates TROP-2 overexpression as an essential prognostic marker and a potential therapeutic target in TNBC. The results endorse the use of TROP-2 expression levels for patient categorization, thereby advancing the implementation of personalized treatment strategies and accelerating the progression towards precision oncology.
三阴性乳腺癌（TNBC）的特点是侵袭性强且治疗选择有限，这主要是由于缺乏雌激素受体（ER）、孕激素受体（PR）和人表皮生长因子受体2（HER2）的表达。TROP-2是一种跨膜糖蛋白，在包括胰腺癌、胃癌和卵巢癌在内的一系列高侵袭性癌症中显著过表达。这种过表达使TROP-2成为关键的预后生物标志物和有前景的治疗干预靶点。
本研究探讨TNBC中TROP-2表达与临床病理特征之间的相关性，评估其作为预后指标和靶向精准治疗候选指标的效用。
对2016年1月至2019年12月期间埃及开罗大学国家癌症研究所的80例TNBC患者样本进行回顾性分析。使用免疫组织化学评估福尔马林固定、石蜡包埋（FFPE）组织中的TROP-2表达。收集包括患者人口统计学、肿瘤特征、治疗方式和生存结果在内的临床和病理数据。将TROP-2表达与临床病理变量和生存指标（总生存期，OS；无病生存期，DFS）进行相关性分析。
78%的病例中观察到TROP-2高表达，在强度、阳性细胞比例和H评分方面表现出显著的异质性。TROP-2表达与更大的肿瘤尺寸和更晚期的淋巴结受累相关，表明其对肿瘤侵袭性有影响。TROP-2强度和H评分升高与较差的总生存期（OS；p分别为0.003和0.007）和无病生存期（DFS；两者p均为0.002）显著相关。多变量分析显示，TROP-2强度、表达百分比和H评分是OS的独立预测因素（p分别为0.02、0.001和0.012）。同样，这些变量被确定为DFS的独立预后指标，p值分别为0.002、0.009和0.002，具有显著性。
我们的研究证实TROP-2过表达是TNBC中一个重要的预后标志物和潜在的治疗靶点。研究结果支持利用TROP-2表达水平对患者进行分类，从而推进个性化治疗策略的实施，并加快向精准肿瘤学的发展进程。
