Prognostic Value of Immunohistochemical Expressions of the Stem Cell Biomarker "LGR5" and the Proliferation Biomarker "TPX2" in Colorectal Carcinoma

O. Harb, Abdelmonem Awad Hegazy, L. Gertallah, R. Haggag, S. Shorbagy
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Abstract

Aim: Colorectal carcinoma (CRC) is the commonest and most deathly malignant gastrointestinal tumors. Carcinogenic process starts in a group of cancer cells, called cancer stem cells (CSCs) having the ability to start and maintain tumor growth and invasion. In order to detect and remove colon CSCs, a selective biomarker "LGR5 (leucine-rich-repeat-containing G-protein-coupled receptor 5)" might be required. At the same time, an abnormal expression of TPX2 (targeting protein for xenopus kinesin-like protein 2) has been found to be related to the development and progression of tumors. We aimed to evaluate the immunohistochemical expressions of LGR5 and TPX2 in CRC in a trial to clarify their relations to proliferation and metastasis of CRC, and hence its prognosis. Methods: Immunohistochemical staining of both LGR5 and TPX2 was assessed in sections from sixty paraffin blocks of CRC . The relationships between their levels of expressions with the clinicopathological parameters and patient outcome were statistically analyzed. Results: The immunoexpression of LGR5 in CRC was signifi­cantly positively correlated with location of the tumor, grade, stage, local recurrence, lymph node and distant metastasis (p <0.001). The expression of TPX2 in CRC was also found to be signifi­cantly correlated with the previous parameters (p <0.001). High LGR5 and TPX2 immunohistochemical expressions were strongly correlated with worse 3-year overall survival (OS), local recurrence free survival (LRFS) and distant metastases free survival (DMFS) (P <0.001). Conclusion: High immunohistochemical expressions of both LGR5 and TPX2 and the positive correlation between both of them represent signs of poor prognosis of CRC.
大肠癌干细胞生物标志物“LGR5”和增殖生物标志物“TPX2”免疫组化表达的预后价值
目的:结直肠癌是最常见、最致命的胃肠道恶性肿瘤。致癌过程始于一组癌细胞,称为癌症干细胞(CSCs),具有启动和维持肿瘤生长和侵袭的能力。为了检测和去除结肠CSCs,可能需要一种选择性的生物标志物“LGR5(亮氨酸富重复-含g蛋白偶联受体5)”。同时发现TPX2 (xenopus kinase -like protein 2的靶蛋白)的异常表达与肿瘤的发生发展有关。我们旨在通过研究LGR5和TPX2在结直肠癌中的免疫组化表达,阐明其与结直肠癌增殖转移及预后的关系。方法:对结直肠癌60块石蜡切片进行LGR5和TPX2免疫组化染色。统计分析其表达水平与临床病理参数及患者转归的关系。结果:LGR5在结直肠癌中的免疫表达与肿瘤部位、分级、分期、局部复发、淋巴结及远处转移呈显著正相关(p <0.001)。TPX2在CRC中的表达也与上述参数显著相关(p <0.001)。高LGR5和TPX2免疫组化表达与较差的3年总生存期(OS)、局部无复发生存期(LRFS)和远处无转移生存期(DMFS)密切相关(P <0.001)。结论:LGR5和TPX2免疫组化表达均较高,且两者呈正相关,是结直肠癌预后不良的标志。
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