Department of Clinical Pathomorphology, Collegium Medicum in Bydgoszcz, Sklodowskiej-Curie Str. 9, 85-094, Bydgoszcz, Poland.
Nicolaus Copernicus University, Toruń, Poland.
J Cancer Res Clin Oncol. 2020 Oct;146(10):2547-2557. doi: 10.1007/s00432-020-03314-7. Epub 2020 Jul 15.
Colorectal cancer (CRC) constitutes one of the most prevalent malignancies in the world. Recent research suggests that cancer stem cells (CSCs) are responsible for tumor cell's malignant behavior in CRC. This study has been designed to determinate clinical implications of CSC markers: CD44, DCLK1, Lgr5, and ANXA2 in CRC.
The study was performed on tissue samples which were collected from 89 patients undergoing colectomy. Formalin-fixed paraffin-embedded tissue blocks with representative tumor areas were identified and corded. Immunohistochemical staining was performed using anti-CD44, anti-LGR5, anti-ANXA2, and anti-DCLK1 antibodies. The H-score system was utilized to determine the immunointensity of CRC cells.
The lower expression of Lgr5 was significantly correlated with the presence of lymph-node metastases (p = 0.011), while high expression of Lgr5 was statistically significant in vascular invasion in examined cancer tissue samples (p = 0.027). Moreover, a high H-score value of Lgr5 expression was significantly related to a reduced overall survival rate (p = 0.043).
Our results suggest a strong relationship between CSC marker Lgr5 and vascular invasion, presence of lymph-node metastasis, and overall poor survival. The presence of Lgr5 might be an unfavorable prognostic factor, and its high level in cancer tissue is related to an aggressive course. This marker could also be used to access the effectiveness of the treatment.
结直肠癌(CRC)是世界上最常见的恶性肿瘤之一。最近的研究表明,癌症干细胞(CSC)是 CRC 中肿瘤细胞恶性行为的原因。本研究旨在确定 CSC 标志物 CD44、DCLK1、Lgr5 和 ANXA2 在 CRC 中的临床意义。
该研究对 89 名接受结肠切除术的患者的组织样本进行了研究。确定并记录了具有代表性肿瘤区域的福尔马林固定石蜡包埋组织块。使用抗 CD44、抗 LGR5、抗 ANXA2 和抗 DCLK1 抗体进行免疫组织化学染色。利用 H 评分系统来确定 CRC 细胞的免疫强度。
Lgr5 的低表达与淋巴结转移的存在显著相关(p=0.011),而在检查的癌组织样本中,Lgr5 的高表达与血管侵犯具有统计学意义(p=0.027)。此外,Lgr5 表达的高 H 评分值与总生存率降低显著相关(p=0.043)。
我们的结果表明,CSC 标志物 Lgr5 与血管侵犯、淋巴结转移和总体不良生存之间存在很强的关系。Lgr5 的存在可能是一个不利的预后因素,其在癌组织中的高水平与侵袭性病程有关。该标志物还可用于评估治疗的效果。