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表皮生长因子受体2在乳腺癌患者中的表达及其与肿瘤浸润淋巴细胞和临床病理特征的关系。

The expression of epidermal growth factor receptor 2 and its relationship with tumor-infiltrating lymphocytes and clinical pathological features in breast cancer patients.

作者信息

Li Yingying, Tang Hui, Yang Xiangjun, Men Nan

机构信息

Department of Pathology, Tangshan Maternal and Child Health Hospital, Tangshan, Hebei, 063000, China.

Department of Pathology, North China University of Science and Technology Affiliated Hospital, Tangshan, Hebei, 063000, China.

出版信息

Open Life Sci. 2025 Jul 15;20(1):20251113. doi: 10.1515/biol-2025-1113. eCollection 2025.

Abstract

Breast cancer (BC) is a common malignant tumor with a frequent occurrence in women, and its occurrence and progression are influenced by various factors. This work aimed to investigate the expression of human epidermal growth factor receptor-2 (HER-2) in BC and its relationship with tumor-infiltrating lymphocytes (TILs) and the clinical pathological features of BC patients. Data from 470 BC patients were collected, and TIL levels were assessed. Immunohistochemistry (IHC) was performed to further analyze the relationship between TILs and clinical pathological parameters, as well as the expression of CD8 and HER-2. Immunohistochemical results revealed that the HER-2-positive expression rate was 28.72% (135/470), and its expression intensity significantly increased with higher histological grades (low grade: 15.2%, moderate grade: 28.5%, high grade: 42.6%, < 0.05). CD8-positive cells were predominantly located in the tumor stroma, with a positive rate of 56.38% (265/470). Moreover, the positive expression intensity in the high TIL level group was significantly higher than in the low TIL level group (high TIL group: 78.9%, low TIL group: 35.4%, < 0.05). The statistical results indicated that 37.45% (176/470) of cases exhibited no or low TIL levels, 42.34% (199/470) showed moderate TIL levels, and 20.21% (95/470) presented high TIL levels. TIL levels were significantly associated with histological grade of BC (percentage of high-grade cases in the high TIL group: 65.3%, in the low TIL group: 22.1%, < 0.05), Ki-67 index (high TIL group: 45.2% ± 12.3%, low TIL group: 25.6% ± 10.8%, < 0.05), vascular tumor embolism (VTE) (VTE-positive rate in the high TIL group: 38.9%, in the low TIL group: 12.4%, < 0.05), lymph node metastasis (LNM) (LNM-positive rate in the high TIL group: 52.6%, in the low TIL group: 28.4%, < 0.05), and estrogen receptor (ER) expression (ER-negative rate in the high TIL group: 68.4%, in the low TIL group: 32.1%, < 0.05). Spearman correlation analysis revealed a positive correlation between TILs and HER-2 ( = 0.149, = 0.002), as well as CD8 ( = 0.593, = 0.001). Analysis of the GEPIA database showed that patients with high HER-2 expression had significantly lower disease-free survival (DFS) compared to those with low expression (hazard ratio [HR] = 1.45, = 0.003), while patients with high CD8 expression exhibited significantly higher DFS than those with low expression (HR = 0.72, = 0.001). In HER-2-positive BC patients, TIL levels were positively correlated with HER-2 and CD8 expression (high HER-2 expression group: TIL high expression rate 48.6%, low HER-2 expression group: TIL high expression rate 15.2%, < 0.05). TIL levels in HER-2-positive BC patients were positively correlated with both HER-2 and CD8 expression. TIL levels were closely related to the prognosis of BC patients, which may provide a theoretical basis for precision treatment in BC.

摘要

乳腺癌(BC)是一种常见的恶性肿瘤,在女性中发病率较高,其发生和进展受多种因素影响。本研究旨在探讨人表皮生长因子受体2(HER-2)在乳腺癌中的表达及其与肿瘤浸润淋巴细胞(TILs)和乳腺癌患者临床病理特征的关系。收集了470例乳腺癌患者的数据,并评估了TIL水平。采用免疫组织化学(IHC)进一步分析TILs与临床病理参数之间的关系,以及CD8和HER-2的表达。免疫组织化学结果显示,HER-2阳性表达率为28.72%(135/470),其表达强度随组织学分级升高而显著增加(低级别:15.2%,中级别:28.5%,高级别:42.6%,P<0.05)。CD8阳性细胞主要位于肿瘤间质,阳性率为56.38%(265/470)。此外,高TIL水平组的阳性表达强度显著高于低TIL水平组(高TIL组:78.9%,低TIL组:35.4%,P<0.05)。统计结果表明,37.45%(176/470)的病例TIL水平无或低,42.34%(199/470)表现为中度TIL水平,20.21%(95/470)呈现高TIL水平。TIL水平与乳腺癌的组织学分级显著相关(高TIL组高级别病例百分比:65.3%,低TIL组:22.1%,P<0.05),与Ki-67指数相关(高TIL组:45.2%±12.3%,低TIL组:25.6%±10.8%,P<0.05),与血管肿瘤栓塞(VTE)相关(高TIL组VTE阳性率:38.9%,低TIL组:12.4%,P<0.05),与淋巴结转移(LNM)相关(高TIL组LNM阳性率:52.6%,低TIL组:28.4%,P<0.05),与雌激素受体(ER)表达相关(高TIL组ER阴性率:68.4%,低TIL组:32.1%,P<0.05)。Spearman相关性分析显示TILs与HER-2呈正相关(r=0.149,P=0.002),与CD8也呈正相关(r=0.593,P=0.001)。GEPIA数据库分析显示,HER-2高表达患者的无病生存期(DFS)显著低于低表达患者(风险比[HR]=1.45,P=0.003),而CD8高表达患者的DFS显著高于低表达患者(HR=0.72,P=0.001)。在HER-2阳性乳腺癌患者中,TIL水平与HER-2和CD8表达呈正相关(HER-2高表达组:TIL高表达率48.6%,HER-2低表达组:TIL高表达率15.2%,P<0.05)。HER-2阳性乳腺癌患者的TIL水平与HER-2和CD8表达均呈正相关。TIL水平与乳腺癌患者的预后密切相关,这可能为乳腺癌的精准治疗提供理论依据。

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