PDF(Pubmed)
Abstract：
BACKGROUND: The missing requirement for resection for the majority of hepatic hemangiomas (HH) and tissue scarcity for rare diseases such as hepatic epithelioid hemangioendotheliomas (HEHE) complicate the characterization of the spatial immunovascular niche of these benign and malignant vascular neoplastic diseases.
METHODS: Two tissue cohorts containing 98 HHs and 13 HEHEs were used to study entity-specific and disease stage-specific endothelial cell (EC) phenotype and immune cell abundance. Using semiquantitative assessment, annotation-based cell classifiers, digital cell detection on whole slides, and tissue microarrays, we quantified 23 immunologic and vascular niche-associated markers and correlated this with clinicopathologic data.
RESULTS: Both HH and HEHE ECs were characterized by a CD31high, CD34high, FVIII-related antigenhigh expression phenotype with entity-specific expression differences of sinusoidal EC markers Stabilin1, Stabilin2, CD32, and Lymphatic Vessel Endothelial Hyaluronan Receptor 1 (LYVE-1). Cell detection identified an HH margin-prevailing immunologic response dominated by Myeloperoxidase+ (MPO+) macrophages, CD3+ and CD8+ T cell subsets, and B cells (CD20+, CD79A+). In HEHE, increased CD68+ and CD20+ cell demarcation of lesion margins was observed, while CD3+ and CD8+ T cells were equally detectable both marginally and intralesionally. Stage-specific pairwise correlation analysis of HH and HEHE revealed disease entity-specific immunologic infiltration patterns as seen by high CD117+ cell numbers in HH, while HEHE samples showed increased CD3+ T cell infiltration.
CONCLUSIONS: ECs in HH and HEHE share a continuous EC expression phenotype, while the expression of sinusoidal EC markers is more highly retained in HEHE. These phenotypic differences are associated with a unique and disease-specific immunovascular landscape.
METHODS: Two tissue cohorts containing 98 HHs and 13 HEHEs were used to study entity-specific and disease stage-specific endothelial cell (EC) phenotype and immune cell abundance. Using semiquantitative assessment, annotation-based cell classifiers, digital cell detection on whole slides, and tissue microarrays, we quantified 23 immunologic and vascular niche-associated markers and correlated this with clinicopathologic data.
RESULTS: Both HH and HEHE ECs were characterized by a CD31high, CD34high, FVIII-related antigenhigh expression phenotype with entity-specific expression differences of sinusoidal EC markers Stabilin1, Stabilin2, CD32, and Lymphatic Vessel Endothelial Hyaluronan Receptor 1 (LYVE-1). Cell detection identified an HH margin-prevailing immunologic response dominated by Myeloperoxidase+ (MPO+) macrophages, CD3+ and CD8+ T cell subsets, and B cells (CD20+, CD79A+). In HEHE, increased CD68+ and CD20+ cell demarcation of lesion margins was observed, while CD3+ and CD8+ T cells were equally detectable both marginally and intralesionally. Stage-specific pairwise correlation analysis of HH and HEHE revealed disease entity-specific immunologic infiltration patterns as seen by high CD117+ cell numbers in HH, while HEHE samples showed increased CD3+ T cell infiltration.
CONCLUSIONS: ECs in HH and HEHE share a continuous EC expression phenotype, while the expression of sinusoidal EC markers is more highly retained in HEHE. These phenotypic differences are associated with a unique and disease-specific immunovascular landscape.
摘要：
背景：大多数肝血管瘤（HH）的切除要求缺失，而罕见疾病如肝上皮样血管内皮瘤（HEHE）的组织稀缺使这些良性和恶性血管肿瘤疾病的空间免疫血管生态位的表征复杂化。
方法：使用包含98个HHs和13个HEHE的两个组织队列来研究实体特异性和疾病阶段特异性内皮细胞（EC）表型和免疫细胞丰度。使用半定量评估，基于注释的单元格分类器，整个幻灯片上的数字细胞检测，和组织微阵列，我们量化了23项免疫和血管生态位相关标志物,并将其与临床病理数据相关联.
结果：HH和HEHEECs均以CD31高，CD34高,FVIII相关抗原高表达表型与正弦EC标记物Stabilin1、Stabilin2、CD32和淋巴管内皮透明质酸受体1(LYVE-1)的实体特异性表达差异。细胞检测确定由髓过氧化物酶+(MPO+)巨噬细胞主导的HH边缘占优势的免疫应答,CD3+和CD8+T细胞亚群，和B细胞（CD20+，CD79A+)。在赫赫,病变边缘CD68+和CD20+细胞分界增加，而CD3+和CD8+T细胞在边缘和细胞内同样可检测到。HH和HEHE的阶段特异性成对相关性分析揭示了疾病实体特异性免疫浸润模式，如HH中的高CD117细胞数所示，而HEHE样本显示CD3+T细胞浸润增加。
结论：HH和HEHE中的EC具有连续的EC表达表型，而正弦EC标志物的表达在HEHE中保留得更高。这些表型差异与独特的疾病特异性免疫血管景观有关。
方法：使用包含98个HHs和13个HEHE的两个组织队列来研究实体特异性和疾病阶段特异性内皮细胞（EC）表型和免疫细胞丰度。使用半定量评估，基于注释的单元格分类器，整个幻灯片上的数字细胞检测，和组织微阵列，我们量化了23项免疫和血管生态位相关标志物,并将其与临床病理数据相关联.
结果：HH和HEHEECs均以CD31高，CD34高,FVIII相关抗原高表达表型与正弦EC标记物Stabilin1、Stabilin2、CD32和淋巴管内皮透明质酸受体1(LYVE-1)的实体特异性表达差异。细胞检测确定由髓过氧化物酶+(MPO+)巨噬细胞主导的HH边缘占优势的免疫应答,CD3+和CD8+T细胞亚群，和B细胞（CD20+，CD79A+)。在赫赫,病变边缘CD68+和CD20+细胞分界增加，而CD3+和CD8+T细胞在边缘和细胞内同样可检测到。HH和HEHE的阶段特异性成对相关性分析揭示了疾病实体特异性免疫浸润模式，如HH中的高CD117细胞数所示，而HEHE样本显示CD3+T细胞浸润增加。
结论：HH和HEHE中的EC具有连续的EC表达表型，而正弦EC标志物的表达在HEHE中保留得更高。这些表型差异与独特的疾病特异性免疫血管景观有关。
