Division of Breast and Endocrine Surgery, Graduate School of Medicine, Gunma University, Gunma, Japan
Department of General Surgical Science, Graduate School of Medicine, Gunma University, Gunma, Japan.
In Vivo. 2020 Sep-Oct;34(5):2641-2646. doi: 10.21873/invivo.12082.
BACKGROUND/AIM: Vascular endothelial growth factor-A (VEGF-A), an important angiogenic factor, has been reported to effect cancer growth and development. Recent reports indicated that anti-VEGF therapy has an important effect of enhancing anti-tumor immunity in various cancers. In the current study, we investigated the relationship between VEGF-A expression and immunological factors, including programmed cell death ligand 1 (PD-L1) and the degrees of stromal tumor-infiltrating lymphocytes (TILs) in breast cancer.
This study enrolled 97 cases with invasive breast cancer who had undergone surgery without preoperative therapy. The grades of stromal-TILs were evaluated using the criteria of the International Working Group for TILs in breast cancer: low, intermediate, and high. VEGF-A and PD-L1 positivity were evaluated by immunohistochemistry. The relationship between VEGF-A expression and the expression of PD-L1 and TILs was investigated.
Among the 97 cases, 37 (38.1%) had positive VEGF-A expression in the breast tumor. We divided the cases in two groups based on the VEGF-A expression levels. The analysis revealed that PD-L1 positivity was significantly associated with VEGF-A expression in the breast tumor (29.7% vs. 10.0%, p=0.014). Among the cases with positive PD-L1, 36.7% of VEGF-positive cases and none of VEGF-negative cases had low TILs in the breast tumor.
VEGF-A expression in breast cancer may reflect PD-L1 expression in the tumor. VEGF-A may act as a negative biomarker of TILs in PD-L1-positive breast cancer. Our results suggest that VEGF-A may be predictive of immunological features and may serve as a useful biomarker for immuno-targeting therapy in patients with breast cancer.
背景/目的:血管内皮生长因子 A(VEGF-A)是一种重要的血管生成因子,已被报道对癌症的生长和发展有影响。最近的报告表明,抗 VEGF 治疗对各种癌症的抗肿瘤免疫具有重要作用。在本研究中,我们研究了 VEGF-A 表达与免疫因子(包括程序性死亡配体 1(PD-L1)和间质肿瘤浸润淋巴细胞(TILs)程度)之间的关系在乳腺癌中。
本研究纳入了 97 例接受手术治疗且无术前治疗的浸润性乳腺癌患者。间质 TILs 分级采用乳腺癌间质 TILs 国际工作组的标准:低、中、高。采用免疫组织化学法评价 VEGF-A 和 PD-L1 阳性率。研究了 VEGF-A 表达与 PD-L1 和 TILs 表达的关系。
在 97 例病例中,37 例(38.1%)乳腺癌肿瘤中存在 VEGF-A 表达阳性。我们根据 VEGF-A 表达水平将病例分为两组。分析显示,乳腺癌肿瘤中 PD-L1 阳性与 VEGF-A 表达显著相关(29.7%比 10.0%,p=0.014)。在 PD-L1 阳性的病例中,36.7%的 VEGF 阳性病例和 VEGF 阴性病例的乳腺癌肿瘤中 TILs 水平较低。
乳腺癌中 VEGF-A 的表达可能反映肿瘤中 PD-L1 的表达。VEGF-A 可能是 PD-L1 阳性乳腺癌中 TILs 的阴性生物标志物。我们的研究结果表明,VEGF-A 可能预测免疫特征,并可能成为乳腺癌免疫靶向治疗的有用生物标志物。