Zubareva Evgeniya Yu, Senchukova Marina A, Saidler Natalia V
Department of Oncology, Orenburg State Medical University, Orenburg 460021, Orenburgskaya Oblast, Russia.
Department of Pathology, Orenburg Regional Cancer Clinic, Orenburg 460021, Orenburgskaya Oblast, Russia.
World J Exp Med. 2025 Jun 20;15(2):102761. doi: 10.5493/wjem.v15.i2.102761.
Breast cancer (BC) continues to occupy a leading position in terms of morbidity and mortality from malignant neoplasms among the female population. One of the promising markers associated with BC progression is programmed death ligand 1 (PD-L1). Previously, we investigated PD-L1 expression in BC a new antibody against programmed cell death protein 1 ligand 1 (PDCD1 LG1) and reported that high PDCD1 LG1 expression in tumor cells is an independent factor for a high risk of regional metastasis in patients with BC. However, the prognostic significance of PDCD1 LG1 expression in BC stromal cells has not been adequately studied.
To study the features of PDCD1 LG1 expression in BC stromal cells and its relationship with BC clinicopathological characteristics.
In a prospective single-center observational study, tumor samples from 148 patients with newly diagnosed BC were examined. The tumor sections were immunohistochemically stained with antibodies against PDCD1 LG1. In the tumor samples, the PDCD1 LG1-positive lymphocyte (PDCD1 LG1+ LF) score, presence of nuclear PDCD1 LG1 expression in the LFs, PDCD1 LG1 expression in polymorphic cell infiltrates (PDCD1 LG1+ polymorphic cell infiltrates [PCIs]), and cells of the fibroblastic stroma and endothelial cells of the tumor microvessels were assessed. Statistical analyses were performed using Statistica 10.0 software.
A PDCD1 LG1+ LF score ≥ 3 was detected more often at stages N0 and N3 than at N1 and N2 ( = 0.03). Moderate and pronounced PDCD1 LG1+ PCIs and the presence of PDCD1 LG1+ fibroblastic stroma were associated with negative estrogen receptor status ( = 0.0008 and = 0.03, respectively), human epidermal growth factor receptor 2-positive (HER2+) BC ( < 0.00001 and = 0.0005), and luminal B HER2+, non-luminal HER2+ and triple-negative BC ( < 0.00001 and = 0.004). The risk of metastasis to regional lymph nodes (RLNs) depend on lymphovascular invasion (LVI) and the PDCD1 LG1+ LF score. In the absence of LVI and a PDCD1 LG1+ LF score < 3 or ≥ 3, metastases in RLNs were absent in 66.6% and 93.9% of patients with BC, respectively. In the presence of LVI and a PDCD1 LG1+ LF score < 3 or ≥ 3, metastases in RLNs were detected in 82.6% and 92.7% of patients with BC, respectively.
The results indicated that the combined assessment of the PDCD1 LG1+ LF score and LVI can improve the accuracy of predicting the risk of metastasis to RLNs in patients with BC.
在女性人群中,乳腺癌(BC)在恶性肿瘤的发病率和死亡率方面继续占据领先地位。与BC进展相关的有前景的标志物之一是程序性死亡配体1(PD-L1)。此前,我们使用一种针对程序性细胞死亡蛋白1配体1(PDCD1 LG1)的新抗体研究了BC中的PD-L1表达,并报告肿瘤细胞中高PDCD1 LG1表达是BC患者区域转移高风险的独立因素。然而,PDCD1 LG1在BC基质细胞中的预后意义尚未得到充分研究。
研究PDCD1 LG1在BC基质细胞中的表达特征及其与BC临床病理特征的关系。
在一项前瞻性单中心观察性研究中,对148例新诊断的BC患者的肿瘤样本进行了检查。肿瘤切片用抗PDCD1 LG1抗体进行免疫组织化学染色。在肿瘤样本中,评估了PDCD1 LG1阳性淋巴细胞(PDCD1 LG1+ LF)评分、LF中核PDCD1 LG1表达的存在情况、多形细胞浸润中PDCD1 LG1的表达(PDCD1 LG1+多形细胞浸润[PCI])以及肿瘤微血管的成纤维细胞基质和内皮细胞中的表达。使用Statistica 10.0软件进行统计分析。
与N1和N2期相比,在N0和N3期更常检测到PDCD1 LG1+ LF评分≥3(P = 0.03)。中度和明显的PDCD1 LG1+ PCI以及PDCD1 LG1+成纤维细胞基质的存在与雌激素受体阴性状态相关(分别为P = 0.0008和P = 0.03)、人表皮生长因子受体2阳性(HER2+)BC(P < 0.00001和P = 0.0005)以及管腔B HER2+、非管腔HER2+和三阴性BC(P < 0.00001和P = 0.004)。区域淋巴结(RLN)转移风险取决于淋巴管浸润(LVI)和PDCD1 LG1+ LF评分。在无LVI且PDCD1 LG1+ LF评分<3或≥3的情况下,BC患者中分别有66.6%和93.9%的患者无RLN转移。在有LVI且PDCD1 LG1+ LF评分<3或≥3的情况下,BC患者中分别有82.6%和92.7%的患者检测到RLN转移。
结果表明,联合评估PDCD1 LG1+ LF评分和LVI可提高预测BC患者RLN转移风险的准确性。