Institute of Pathology, University Medical Center Mainz, Mainz, Germany.
Tissue Biobank, University Medical Center Mainz, Mainz, Germany.
Pathobiology. 2024;91(3):219-229. doi: 10.1159/000535201. Epub 2023 Nov 14.
Tumor cells use adhesion molecules like CD15 or sialylCD15 (sCD15) for metastatic spreading. We analyzed the expression of CD15 and sCD15 in clear cell renal cell carcinoma (ccRCC) regarding prognosis.
A tissue microarray containing tissue specimens of 763 patients with ccRCC was immunohistochemically stained for CD15 and sCD15, their expression quantified using digital image analysis, and the impact on patients' survival analyzed. The cell lines 769p and 786o were stimulated with CD15 or control antibody in vitro and the effects on pathways activating AP-1 and tumor cell migration were examined.
ccRCC showed a broad range of CD15 and sCD15 expression. A high CD15 expression was significantly associated with favorable outcome (p < 0.01) and low-grade tumor differentiation (p < 0.001), whereas sCD15 had no significant prognostic value. Tumors with synchronous distant metastasis had a significantly lower CD15 expression compared to tumors without any (p < 0.001) or with metachronous metastasis (p < 0.01). Tumor cell migration was significantly reduced after CD15 stimulation in vitro, but there were no major effects on the activating pathways of AP-1.
CD15, but not sCD15, qualifies as a biomarker for risk stratification and as an interesting novel target in ccRCC. Moreover, the data indicate a contribution of CD15 to metachronous metastasis. Further research is warranted to decipher the intracellular pathways of CD15 signaling in ccRCC in order to characterize the CD15 effects on ccRCC more precisely.
肿瘤细胞使用黏附分子,如 CD15 或唾液酸化 CD15(sCD15)进行转移扩散。我们分析了 CD15 和 sCD15 在透明细胞肾细胞癌(ccRCC)中的表达与预后的关系。
使用组织微阵列对 763 例 ccRCC 组织标本进行 CD15 和 sCD15 的免疫组织化学染色,使用数字图像分析定量其表达,并分析对患者生存的影响。体外刺激细胞系 769p 和 786o 用 CD15 或对照抗体,并检查对激活 AP-1 和肿瘤细胞迁移的途径的影响。
ccRCC 表现出广泛的 CD15 和 sCD15 表达。高 CD15 表达与良好的预后显著相关(p < 0.01)和低分化肿瘤(p < 0.001),而 sCD15 无显著预后价值。同步远处转移的肿瘤与无任何(p < 0.001)或异时转移(p < 0.01)的肿瘤相比,CD15 表达明显降低。体外刺激 CD15 后肿瘤细胞迁移明显减少,但对 AP-1 的激活途径没有明显影响。
CD15,但不是 sCD15,可以作为风险分层的生物标志物,也是 ccRCC 中一个有趣的新靶点。此外,数据表明 CD15 有助于异时转移。需要进一步研究以破译 ccRCC 中 CD15 信号转导的细胞内途径,以便更准确地描述 CD15 对 ccRCC 的影响。