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巢蛋白和Fms相关酪氨酸激酶1(FLT1)对肿瘤血管微环境的调控及其在肾细胞癌中的预后意义

Regulation of Tumor Vascular Microenvironment by Nestin and Fms-related Tyrosine Kinase 1 (FLT1) and Their Prognostic Significance in Renal Cell Carcinoma.

作者信息

Elkady Noha, Abdelaziz Reham Ahmed, Abdelmoneum Rasha Adel, Ghonaimy Ahmed S, Allam Dina Mohamed

机构信息

Department of Pathology, Faculty of Medicine, Menoufia University, Shibin Elkom, Egypt.

Department of Clinical Oncology and Nuclear MedicineFaculty of Medicine, Menoufia University, Egypt.

出版信息

Iran J Pathol. 2024;19(3):332-341. doi: 10.30699/IJP.2024.2024190.3266. Epub 2024 Mar 3.

Abstract

BACKGROUND & OBJECTIVE: Hypervascularity is a characteristic feature of renal cell carcinoma (RCC) and microvessel density (MVD) predicts tumor metastasis. Nestin is a stem cell marker that is expressed in proliferating endothelial cells and newly formed vessels and Fms-related tyrosine kinase 1 (FLT1) is a proangiogenic factor. This study aimed to evaluate the expression of Nestin and FLT1 in RCC and their prognostic impact.

METHODS

This retrospective study included sixty cases of RCC after obtaining ethical approval. Sections were immunohistochemically stained by Nestin and FLT1 then their expressions were compared to different clinicopathological parameters. MVD was evaluated using Nestin and CD34 and compared to the different parameters.

RESULTS

Nestin was expressed mainly in endothelial cells of small vessels in 65% of cases while FLT1 was expressed in tumor and endothelial cells in 73.3% of cases. Their expressions were significantly associated with aggressive tumor parameters including larger tumors, high-grade tumors, wider tumor extension, and advanced stage. Moreover, Nestin expression was significantly associated with metastasis. MVD evaluated by Nestin showed more associations with larger tumors, high-grade tumors, wider tumor extension, advanced stage, and metastasis than MVD measured by CD34. Nestin and FLT1 positivity and high MVD measured by Nestin were significantly associated with short overall survival.

CONCLUSION

Nestin and FLT1 expressions in RCC may be associated with aggressive tumor features and short patients' overall survival. MVD evaluated by Nestin may be correlated with tumor progression and metastasis. Nestin and FLT1 may be used as prognostic biomarkers in RCC.

摘要

背景与目的

血管增多是肾细胞癌(RCC)的一个特征性表现,微血管密度(MVD)可预测肿瘤转移。巢蛋白是一种干细胞标志物,在增殖的内皮细胞和新形成的血管中表达,而Fms相关酪氨酸激酶1(FLT1)是一种促血管生成因子。本研究旨在评估巢蛋白和FLT1在肾细胞癌中的表达及其预后影响。

方法

本回顾性研究经伦理批准,纳入60例肾细胞癌病例。切片用巢蛋白和FLT1进行免疫组织化学染色,然后将它们的表达与不同的临床病理参数进行比较。使用巢蛋白和CD34评估MVD,并与不同参数进行比较。

结果

65%的病例中巢蛋白主要在小血管的内皮细胞中表达,而73.3%的病例中FLT1在肿瘤细胞和内皮细胞中表达。它们的表达与侵袭性肿瘤参数显著相关,包括较大的肿瘤、高级别肿瘤、较宽的肿瘤扩展范围和晚期。此外,巢蛋白表达与转移显著相关。与用CD34测量的MVD相比,用巢蛋白评估的MVD与较大的肿瘤、高级别肿瘤、较宽的肿瘤扩展范围、晚期和转移的相关性更强。巢蛋白和FLT1阳性以及用巢蛋白测量的高MVD与较短的总生存期显著相关。

结论

肾细胞癌中巢蛋白和FLT1的表达可能与侵袭性肿瘤特征和患者较短的总生存期相关。用巢蛋白评估的MVD可能与肿瘤进展和转移相关。巢蛋白和FLT1可用作肾细胞癌的预后生物标志物。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/66b5/11646198/028e271a4d59/ijp-19-332-g001.jpg

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