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血管内皮生长因子受体1(VEGFR1/Flt-1)免疫表达在结直肠癌中的预后意义

Prognostic significance of VEGFR1/Flt-1 immunoexpression in colorectal carcinoma.

作者信息

Al-Maghrabi Jaudah, Gomaa Wafaey, Buhmeida Abdelbaset, Qari Yousif, Al-Qahtani Mohammad, Al-Ahwal Mahmoud

机构信息

Scientific Chair for Colorectal Cancer, King Abdulaziz University, Jeddah, Saudi Arabia,

出版信息

Tumour Biol. 2014 Sep;35(9):9045-51. doi: 10.1007/s13277-014-2124-5. Epub 2014 Jun 9.

Abstract

Colorectal carcinoma (CRC) is a major cause of morbidity and mortality. Vascular endothelial growth factor 1/Fms-like tyrosine kinase 1 (VEGFR1/Flt-1) regulates monocyte migration, recruits endothelial cell progenitors, increases the adhesive properties of natural killer cells and induces of growth factors. Flt-1 is expressed on tumour cells and has been implicated in tumour growth and progression. The objective of this study is to address the relation of Flt-1 expression to tumour prognostication. Paraffin blocks from 143 primary CRC and 48 regional nodal metastases were retrieved from the archives of the Department of Pathology at King Abdulaziz University. Tissue microarrays were designed and constructed. Immunohistochemistry for Flt-1 was performed. Staining intensity and extent of staining were assessed and combined. Results were dichotomised as low expression and high expression. Flt-1 was overexpressed in primary tumours and nodal metastasis (p < 0.001 and 0.001) with no difference between primary and nodal metastasis (p = 0.690). Flt-1 immunoexpression was not associated with the clinicopathological parameters. Flt-1 overexpression was an independent predictor of positive margin status, positive lymphovascular invasion and local disease recurrence (p < 0.001, p < 0.001 and p = 0.003, respectively). Flt-1 was not associated with survival (log-rank = 0.003, p = 0.959). Flt-1 was overexpressed in primary CRC and their nodal metastases. Flt-1 expression was an independent predictor of margin status, lymphovascular invasion and local disease recurrence. Therefore, expression profiling of Flt-1 seems to have a prognostic potential in CRC. However, to elucidate the association of overexpression of Flt-1 with tumour characteristics and prognostication, more in vivo and in vitro molecular investigations are recommended.

摘要

结直肠癌(CRC)是发病和死亡的主要原因。血管内皮生长因子1/类Fms酪氨酸激酶1(VEGFR1/Flt-1)调节单核细胞迁移、募集内皮细胞祖细胞、增加自然杀伤细胞的黏附特性并诱导生长因子。Flt-1在肿瘤细胞上表达,并与肿瘤生长和进展有关。本研究的目的是探讨Flt-1表达与肿瘤预后的关系。从阿卜杜勒阿齐兹国王大学病理学系档案中检索出143例原发性CRC和48例区域淋巴结转移的石蜡块。设计并构建了组织芯片。进行了Flt-1的免疫组织化学检测。评估并合并染色强度和染色范围。结果分为低表达和高表达。Flt-1在原发性肿瘤和淋巴结转移中均过度表达(p<0.001和0.001),原发性肿瘤和淋巴结转移之间无差异(p = 0.690)。Flt-1免疫表达与临床病理参数无关。Flt-1过度表达是切缘阳性状态、阳性淋巴管侵犯和局部疾病复发的独立预测因子(分别为p<0.001、p<0.001和p = 0.003)。Flt-1与生存率无关(对数秩=0.003,p = 0.959)。Flt-1在原发性CRC及其淋巴结转移中过度表达。Flt-1表达是切缘状态、淋巴管侵犯和局部疾病复发的独立预测因子。因此,Flt-1的表达谱似乎在CRC中具有预后潜力。然而,为了阐明Flt-1过度表达与肿瘤特征和预后的关联,建议进行更多的体内和体外分子研究。

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