Center for Ophthalmology, University Eye Hospital, University of Tübingen, Elfriede-Aulhorn-Strasse 7, 72076, Tübingen, Germany.
J Cancer Res Clin Oncol. 2021 May;147(5):1389-1405. doi: 10.1007/s00432-021-03555-0. Epub 2021 Mar 4.
While B-cell activating factor (BAFF) was identified to promote the invasion in other malignancies, its role in the progression of uveal melanoma (UM) still remains unexplored. Here, we analysed the serum level of BAFF in UM patients with regard to its significance as biomarker for the metastases.
In this retrospective study, serum BAFF levels in 173 UM patients (36 with metastases and 137 without), and 23 healthy controls were measured with a multiplexed sandwich ELISA system and then correlated with clinicopathological characteristics such as primary tumor size, tumor location, histological cell type, sex, cancer stage, cytogenetic alterations of chromosome 3, and the metastatic burden. Immunohistochemical staining of 50 UM tissue specimens was also performed to evaluate the expression of BAFF and its receptors BAFF-R and TACI.
The metastatic patients were identified to have significantly higher serum BAFF levels (mean ± SD, 1520.8 ± 1182.1 pg/ml) than those without metastases (950.4 ± 494.6 pg/ml) and controls (810.3 ± 140.5 pg/ml). While no distinctions were detected with regard to tumor location, histological cell type, gender, and monosomy 3, the patients in cancer stages II, III, and IV displayed higher serum BAFF levels than those in stage I. The serum BAFF level was significantly correlated with the metastatic burden. The serum BAFF level of 1120 pg/ml was identified to have the best performance for distinguishing the metastatic patients from non-metastatic patients. In the kinetic study, we noticed that 20.8% of the analysed patients already demonstrated elevated serum BAFF concentrations before the clinical diagnosis of metastases. Positive BAFF staining was detected in the cytoplasm of single tumor cells (in 13 specimens), macrophages (in 12 specimens), and tumor-infiltrating lymphocytes (TILs) (in 13 specimens). The expressions of BAFF-R and TACI were also observed in 17 and 36 of the 50 tested UM specimens, respectively.
Our study first suggests that BAFF might be a promising serum marker for the detection of UM metastases.
虽然 B 细胞激活因子（BAFF）已被确定可促进其他恶性肿瘤的侵袭，但它在葡萄膜黑色素瘤（UM）进展中的作用仍未被探索。在这里，我们分析了 UM 患者的血清 BAFF 水平，以期将其作为转移的生物标志物。
在这项回顾性研究中，使用多重夹心 ELISA 系统测量了 173 名 UM 患者（36 名有转移，137 名无转移）和 23 名健康对照者的血清 BAFF 水平，然后将其与临床病理特征（如原发肿瘤大小、肿瘤位置、组织学细胞类型、性别、癌症分期、染色体 3 的细胞遗传学改变和转移负担）相关联。还对 50 份 UM 组织标本进行了免疫组织化学染色，以评估 BAFF 及其受体 BAFF-R 和 TACI 的表达。
转移性患者的血清 BAFF 水平（平均值±标准差，1520.8±1182.1 pg/ml）明显高于无转移患者（950.4±494.6 pg/ml）和对照组（810.3±140.5 pg/ml）。虽然在肿瘤位置、组织学细胞类型、性别和单体 3 方面没有差异，但在癌症分期 II、III 和 IV 的患者中，血清 BAFF 水平高于分期 I 的患者。血清 BAFF 水平与转移负担显著相关。将 1120 pg/ml 的血清 BAFF 水平作为区分转移性患者和非转移性患者的最佳标准。在动力学研究中，我们注意到在临床诊断转移之前，已有 20.8%的分析患者已经显示出血清 BAFF 浓度升高。在 13 份标本的单个肿瘤细胞、12 份标本的巨噬细胞和 13 份标本的肿瘤浸润淋巴细胞（TIL）的细胞质中检测到 BAFF 染色阳性。在 50 个测试的 UM 标本中，分别有 17 个和 36 个表达 BAFF-R 和 TACI。
我们的研究首次表明，BAFF 可能是检测 UM 转移的有前途的血清标志物。
