肿瘤微血管的容积成像反映了透明细胞肾细胞癌的结局和基因组状态。

IF 3.4 2区 医学 Q1 PATHOLOGY
Yuta Kaneko, Tsukasa Masuda, Kimiharu Takamatsu, Shuji Mikami, Kohei Nakamura, Hiroshi Nishihara, Ryuichi Mizuno, Nobuyuki Tanaka, Mototsugu Oya
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引用次数: 0

摘要

肿瘤结构异质且复杂,二维分析很难获得完整的特征。本研究旨在利用全组织表型和三维光片显微镜观察透明细胞肾细胞癌(ccRCC)肿瘤的体积血管信息并确定其特征。在这里,我们使用诊断免疫标记石蜡包埋清除器官管道进行组织清除、免疫标记和三维成像。通过计算三维密度、血管长度、血管半径和密度曲线,如表达的偏度、峰度和方差,研究了靶向血管的 CD34 和靶向淋巴管的 LYVE-1 的空间分布。然后,我们研究了这些与ccRCC结果和基因改变状态的关联。研究纳入了 46 例 ccRCC 患者的福尔马林固定石蜡包埋肿瘤样本。接收者操作特征曲线分析显示,血管和淋巴管分布与核分级高、肿瘤体积大和存在静脉侵犯等病理因素有关。此外,三维成像参数还对ccRCC患者的生存结果进行了分层。基于体积血管信息参数的基因组改变分析表明,与血管半径相关的PI3K-mTOR通路突变存在显著差异。总之,我们的研究表明,体积血管信息的空间阐释可用于预后,并可作为基因组改变的新生物标志物。高端组织清理技术和容积免疫组化技术可对肿瘤进行三维分析,从而更好地了解肿瘤空间的微血管结构。
本文章由计算机程序翻译,如有差异,请以英文原文为准。

Volumetric imaging of the tumor microvasculature reflects outcomes and genomic states of clear cell renal cell carcinoma

Volumetric imaging of the tumor microvasculature reflects outcomes and genomic states of clear cell renal cell carcinoma

Tumor structure is heterogeneous and complex, and it is difficult to obtain complete characteristics by two-dimensional analysis. The aim of this study was to visualize and characterize volumetric vascular information of clear cell renal cell carcinoma (ccRCC) tumors using whole tissue phenotyping and three-dimensional light-sheet microscopy. Here, we used the diagnosing immunolabeled paraffin-embedded cleared organs pipeline for tissue clearing, immunolabeling, and three-dimensional imaging. The spatial distributions of CD34, which targets blood vessels, and LYVE-1, which targets lymphatic vessels, were examined by calculating three-dimensional density, vessel length, vessel radius, and density curves, such as skewness, kurtosis, and variance of the expression. We then examined those associations with ccRCC outcomes and genetic alteration state. Formalin-fixed paraffin-embedded tumor samples from 46 ccRCC patients were included in the study. Receiver operating characteristic curve analyses revealed the associations between blood vessel and lymphatic vessel distributions and pathological factors such as a high nuclear grade, large tumor size, and the presence of venous invasion. Furthermore, three-dimensional imaging parameters stratified ccRCC patients regarding survival outcomes. An analysis of genomic alterations based on volumetric vascular information parameters revealed that PI3K-mTOR pathway mutations related to the blood vessel radius were significantly different. Collectively, we have shown that the spatial elucidation of volumetric vasculature information could be prognostic and may serve as a new biomarker for genomic alterations. High-end tissue clearing techniques and volumetric immunohistochemistry enable three-dimensional analysis of tumors, leading to a better understanding of the microvascular structure in the tumor space.

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来源期刊
Journal of Pathology Clinical Research
Journal of Pathology Clinical Research Medicine-Pathology and Forensic Medicine
CiteScore
7.40
自引率
2.40%
发文量
47
审稿时长
20 weeks
期刊介绍: The Journal of Pathology: Clinical Research and The Journal of Pathology serve as translational bridges between basic biomedical science and clinical medicine with particular emphasis on, but not restricted to, tissue based studies. The focus of The Journal of Pathology: Clinical Research is the publication of studies that illuminate the clinical relevance of research in the broad area of the study of disease. Appropriately powered and validated studies with novel diagnostic, prognostic and predictive significance, and biomarker discover and validation, will be welcomed. Studies with a predominantly mechanistic basis will be more appropriate for the companion Journal of Pathology.
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