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Diversity of mutations in the dystrophin gene and details of muscular lesions in porcine dystrophinopathies. 猪肌营养不良症中肌营养不良蛋白基因突变的多样性和肌肉病变的细节。
IF 2.4 2区 农林科学 Q2 PATHOLOGY Pub Date : 2024-05-01 Epub Date: 2023-11-25 DOI: 10.1177/03009858231214028
Yumiko Kamiya, Naoyuki Aihara, Takanori Shiga, Noriyuki Horiuchi, Junichi Kamiie

During meat inspections in pigs, dystrophinopathies are among the muscle lesions targeted for disposal. In this study, the authors examined the lesions and the distribution of dystrophin expression in 25 pigs with dystrophinopathy. In addition, complementary deoxyribonucleic acid (cDNA) sequencing and western blotting were performed in 6 of the 25 cases, all of which were characterized by degeneration, necrosis, and fat replacement of muscle fibers. Comparing the results of immunohistochemistry with anti-dystrophin antibodies that recognized at different sites in the protein, the authors noted that the loss of dystrophin expression was most pronounced in the C-terminus-recognizing antibody (19/25 cases). The authors detected 5 missense mutations and 3 types of shortened transcripts generated by the skipping of exons in the cDNA, which were associated with the pathogenesis. One missense mutation had been reported previously, whereas the remaining mutations identified had not been previously documented in pigs. In the cases with shortened transcripts, normal-sized transcripts were detected together with the defective transcripts, suggesting that these mutations were caused by splicing abnormalities. In addition, they were in-frame mutations, all of which have similar pathogeneses of Becker muscular dystrophy in humans. These cases were 6 months of age and exhibited macroscopic discoloration, fatty replacement, and muscle degeneration, suggesting that the effect of these mutations on skeletal muscle was significant.

在对猪的肉类检查中,肌营养不良病是处理的目标肌肉病变之一。在这项研究中,作者检查了25头肌营养不良病猪的病变和肌营养不良蛋白的表达分布。此外,对25例患者中的6例进行了互补脱氧核糖核酸(cDNA)测序和western blotting,均表现为肌纤维变性、坏死和脂肪替代。将免疫组织化学结果与识别蛋白不同位点的抗肌营养不良蛋白抗体进行比较,作者注意到,在c端识别抗体中,肌营养不良蛋白表达的丧失最为明显(19/25例)。作者检测到5个错义突变和3种由cDNA外显子跳跃产生的缩短转录本,这些突变与发病机制有关。以前曾报道过一种错义突变,而在猪中发现的其余突变以前没有记录。在转录本缩短的病例中,正常大小的转录本与缺陷转录本一起被检测到,这表明这些突变是由剪接异常引起的。此外,它们都是框架内突变,所有这些突变都具有与人类贝克肌萎缩症相似的发病机制。这些病例为6个月大,表现为肉眼变色、脂肪替代和肌肉变性,表明这些突变对骨骼肌的影响是显著的。
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引用次数: 0
PDL1 immunohistochemistry in canine neoplasms: Validation of commercial antibodies, standardization of evaluation, and scoring systems. 犬肿瘤中的PDL1免疫组织化学:商业抗体的验证、评估标准化和评分系统。
IF 2.4 2区 农林科学 Q2 PATHOLOGY Pub Date : 2024-05-01 Epub Date: 2023-11-03 DOI: 10.1177/03009858231209410
Luisa Vera Muscatello, Francesca Gobbo, Giancarlo Avallone, Micaela Innao, Cinzia Benazzi, Giulia D'Annunzio, Donatella Romaniello, Massimo Orioles, Mattia Lauriola, Giuseppe Sarli

Immuno-oncology research has brought to light the paradoxical role of immune cells in the induction and elimination of cancer. Programmed cell death protein 1 (PD1), expressed by tumor-infiltrating lymphocytes, and programmed cell death ligand 1 (PDL1), expressed by tumor cells, are immune checkpoint proteins that regulate the antitumor adaptive immune response. This study aimed to validate commercially available PDL1 antibodies in canine tissue and then, applying standardized methods and scoring systems used in human pathology, evaluate PDL1 immunopositivity in different types of canine tumors. To demonstrate cross-reactivity, a monoclonal antibody (22C3) and polyclonal antibody (cod. A1645) were tested by western blot. Cross-reactivity in canine tissue cell extracts was observed for both antibodies; however, the polyclonal antibody (cod. A1645) demonstrated higher signal specificity. Canine tumor histotypes were selected based on the human counterparts known to express PDL1. Immunohistochemistry was performed on 168 tumors with the polyclonal anti-PDL1 antibody. Only membranous labeling was considered positive. PDL1 labeling was detected both in neoplastic and infiltrating immune cells. The following tumors were immunopositive: melanomas (17 of 17; 100%), renal cell carcinomas (4 of 17; 24%), squamous cell carcinomas (3 of 17; 18%), lymphomas (2 of 14; 14%), urothelial carcinomas (2 of 18; 11%), pulmonary carcinomas (2 of 20; 10%), and mammary carcinomas (1 of 31; 3%). Gastric (0 of 10; 0%) and intestinal carcinomas (0 of 24; 0%) were negative. The findings of this study suggest that PDL1 is expressed in some canine tumors, with high prevalence in melanomas.

免疫生态学研究揭示了免疫细胞在诱导和消除癌症中的矛盾作用。由肿瘤浸润淋巴细胞表达的程序性细胞死亡蛋白1(PD1)和由肿瘤细胞表达的程序化细胞死亡配体1(PDL1)是调节抗肿瘤适应性免疫反应的免疫检查点蛋白。本研究旨在验证犬组织中可买到的PDL1抗体,然后应用人类病理学中使用的标准化方法和评分系统,评估PDL1在不同类型犬肿瘤中的免疫阳性率。为了证明交叉反应性,通过蛋白质印迹测试单克隆抗体(22C3)和多克隆抗体(cod.A1645)。在犬组织细胞提取物中观察到两种抗体的交叉反应性;然而,多克隆抗体(cod.A1645)显示出更高的信号特异性。基于已知表达PDL1的人类对应物来选择犬肿瘤组织类型。用多克隆抗PDL1抗体对168例肿瘤进行免疫组化。只有膜标记被认为是阳性的。PDL1标记在肿瘤和浸润性免疫细胞中均被检测到。以下肿瘤为免疫阳性:黑色素瘤(17例,100%)、肾细胞癌(17例中4例,24%)、鳞状细胞癌(3例,18%)、淋巴瘤(2例,14%)、尿路上皮癌(2例;11%)、肺癌(20例中2例,10%)和乳腺癌(1例,31%;3%)。胃癌(0/10;0%)和肠癌(0/24;0%)为阴性。这项研究的结果表明,PDL1在一些犬肿瘤中表达,在黑色素瘤中发病率很高。
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引用次数: 0
PD-L1 mRNA and protein expression in canine mammary carcinomas: Correlation with histopathological grade and molecular markers. 犬乳腺癌中 PD-L1 mRNA 和蛋白的表达:与组织病理学分级和分子标记物的相关性。
IF 2.4 2区 农林科学 Q2 PATHOLOGY Pub Date : 2024-05-01 Epub Date: 2024-01-28 DOI: 10.1177/03009858241226621
Min-Kyung Bae, Yeong-Ung Ko, Byung-Joon Seung, Jung-Hyang Sur, Nong-Hoon Choe

Programmed death ligand 1 (PD-L1) is an immune checkpoint molecule that plays a crucial role in regulating antitumor immune responses. Canine mammary carcinomas (CMCs) are common tumors of dogs. Despite extensive studies on the heterogeneity of CMCs, there is still a lack of effective precision therapies for the treatment of CMCs. In this study, we aimed to investigate the correlation between PD-L1 mRNA and protein expression in CMCs and explore its association with histopathological grade and molecular markers, including the estrogen receptor, epidermal growth factor receptor 2, and cytokeratin 5/6 (CK5/6). Formalin-fixed paraffin-embedded samples were evaluated for PD-L1 mRNA expression using RNA in situ hybridization and PD-L1 protein expression using immunohistochemistry. We observed no substantial correlation between PD-L1 mRNA and protein expression in CMCs; however, PD-L1 mRNA levels were significantly higher in grade 3 than in grade 1 tumors (P = .001). In addition, we observed a positive correlation between PD-L1 protein expression and CK5/6 expression in CMCs (P = .032). These findings suggest that PD-L1 expression in CMCs is heterogeneous and may be regulated post-transcriptionally. Further studies are needed to explore the prognostic and therapeutic implications of PD-L1 expression in different molecular subtypes of CMCs and their potential as predictive biomarkers for immunotherapy.

程序性死亡配体 1(PD-L1)是一种免疫检查点分子,在调节抗肿瘤免疫反应中发挥着至关重要的作用。犬乳腺癌(CMC)是犬的常见肿瘤。尽管对 CMCs 的异质性进行了广泛研究,但目前仍缺乏有效的精准疗法来治疗 CMCs。在本研究中,我们旨在研究 CMCs 中 PD-L1 mRNA 和蛋白表达的相关性,并探讨其与组织病理学分级和分子标记物(包括雌激素受体、表皮生长因子受体 2 和细胞角蛋白 5/6 (CK5/6))的关联。我们使用 RNA 原位杂交技术评估了福尔马林固定石蜡包埋样本的 PD-L1 mRNA 表达情况,并使用免疫组化技术评估了 PD-L1 蛋白表达情况。我们观察到,CMCs 中 PD-L1 mRNA 和蛋白表达之间没有实质性关联;但是,3 级肿瘤的 PD-L1 mRNA 水平明显高于 1 级肿瘤(P = .001)。此外,我们还观察到 CMCs 中 PD-L1 蛋白表达与 CK5/6 表达呈正相关(P = .032)。这些发现表明,PD-L1在CMCs中的表达是异质性的,可能受到转录后的调控。需要进一步研究探讨不同分子亚型 CMCs 中 PD-L1 表达对预后和治疗的影响,以及其作为免疫疗法预测性生物标志物的潜力。
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引用次数: 0
Diagnostic challenge in veterinary pathology: Detection of BRAFV595E mutation in a dog with follicular cystitis and flat urothelial lesion with atypia. 兽医病理学诊断挑战:在一只患有滤泡性膀胱炎和扁平尿道非典型病变的狗体内检测到 BRAFV595E 突变。
IF 2.3 2区 农林科学 Q2 PATHOLOGY Pub Date : 2024-05-01 Epub Date: 2023-12-13 DOI: 10.1177/03009858231217242
James K Chambers, Naohiro Takahashi, Shizuka Kato, Yuko Hashimoto, Yuko Goto-Koshino, Kazuyuki Uchida
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引用次数: 0
Highly pathogenic avian influenza virus H5N1 infection in skua and gulls in the United Kingdom, 2022. 2022 年英国鸥鼬和海鸥感染高致病性禽流感病毒 H5N1。
IF 2.4 2区 农林科学 Q2 PATHOLOGY Pub Date : 2024-05-01 Epub Date: 2023-12-23 DOI: 10.1177/03009858231217224
Fabian Z X Lean, Marco Falchieri, Natalia Furman, Glen Tyler, Caroline Robinson, Paul Holmes, Scott M Reid, Ashley C Banyard, Ian H Brown, Catherine Man, Alejandro Núñez

The reemergence of the highly pathogenic avian influenza virus (HPAIV) subtype H5N1 in the United Kingdom in 2021-2022 has caused unprecedented epizootic events in wild birds and poultry. During the summer of 2022, there was a shift in virus transmission dynamics resulting in increased HPAIV infection in seabirds, and consequently, a profound impact on seabird populations. To understand the pathological impact of HPAIV in seabirds, we evaluated the virus antigen distribution and associated pathological changes in the tissues of great skua (Stercorarius skua, n = 8), long-tailed skua (Stercorarius longicaudus, n = 1), European herring gull (Larus argentatus, n = 5), and black-headed gull (Chroicocephalus ridibundus, n = 4), which succumbed to natural infection of HPAIV during the summer of 2022. Cases were collected from Shetland, including Scatness (mainland), No Ness (mainland), Clumlie (mainland), Hermaness (island), Fair Isle (island), Noss (island), and the West Midlands, South East, and South West of England. Grossly, gizzard ulceration was observed in one great skua and pancreatic necrosis was observed in 4 herring gulls, with intralesional viral antigen detected subsequently. Microscopical analysis revealed neuro-, pneumo-, lymphoid-, and cardiomyotropism of HPAIV H5N1, with the most common virus-associated pathological changes being pancreatic and splenic necrosis. Examination of the reproductive tract of the great skua revealed HPAIV-associated oophoritis and salpingitis, and virus replication within the oviductal epithelium. The emergence of HPAIV in seabirds Stercorariidae and Laridae, particularly during summer 2022, has challenged the dogma of HPAIV dynamics, posing a significant threat to wild bird life with potential implications for the reproductive performance of seabirds of conservation importance.

2021-2022 年,高致病性禽流感病毒(HPAIV)亚型 H5N1 在英国再次出现,在野生鸟类和家禽中引发了前所未有的流行病事件。2022 年夏季,病毒传播动态发生了变化,导致海鸟感染 HPAIV 的数量增加,从而对海鸟种群产生了深远影响。为了了解高致病性禽流感病毒对海鸟病理的影响,我们评估了2022年夏季自然感染高致病性禽流感病毒后死亡的大翅鸥(Stercorarius skua,n = 8)、长尾鸥(Stercorarius longicaudus,n = 1)、欧洲鲱鸥(Larus argentatus,n = 5)和黑头鸥(Chroicocephalus ridibundus,n = 4)组织中的病毒抗原分布和相关病理变化。病例收集自设得兰群岛,包括斯卡特尼斯岛(大陆)、诺内斯岛(大陆)、克伦利岛(大陆)、赫尔曼内斯岛(岛屿)、费尔岛(岛屿)、诺斯岛(岛屿)以及英格兰西米德兰兹郡、东南部和西南部。从大体上看,在一只大天鸥身上观察到了肫溃疡,在 4 只鲱鸥身上观察到了胰腺坏死,随后检测到了体内病毒抗原。显微镜分析表明,高致病性禽流感病毒 H5N1 可引起神经、肺、淋巴和心肌炎,最常见的病毒相关病理变化是胰腺和脾脏坏死。对大鼬鼠生殖道的检查发现了与高致病性禽流感相关的输卵管炎和输卵管炎,以及输卵管上皮内的病毒复制。高致病性禽流感病毒出现在海鸟Stercorariidae和Laridae中,尤其是在2022年夏季,这对高致病性禽流感病毒的动态规律提出了挑战,对野生鸟类的生命构成了重大威胁,并对具有重要保护意义的海鸟的繁殖性能产生了潜在影响。
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引用次数: 0
Subcutaneous choriocarcinomas in captive Amargosa voles (Microtus californicus scirpensis). 圈养Amargosa田鼠的皮下绒毛膜癌。
IF 2.3 2区 农林科学 Q2 PATHOLOGY Pub Date : 2024-05-01 Epub Date: 2023-10-13 DOI: 10.1177/03009858231203647
Sebastian E Carrasco, Amanda L Johnson, Kerriann M Casey, Nora Allan, Mia Reed, Janet E Foley, Denise M Imai

Spontaneous choriocarcinomas are rare, highly vascular, malignant trophoblastic tumors that occur in humans and animals. This report describes the unusual spontaneous presentation of 4 choriocarcinomas within the subcutaneous tissues of 4, multiparous but nongravid, Amargosa voles (Microtus californicus scirpensis) from a captive breeding colony. Two subcutaneous neoplasms were composed of multifocal discohesive and infiltrative aggregates of medium to large trophoblasts and cytotrophoblasts within a fibrovascular stroma. Neoplastic cells were associated with variably sized thrombi and cavitary areas of hemorrhage and necrosis. Two subcutaneous tumors were predominantly composed of expansile, blood-filled, cystic spaces lined by neoplastic cytotrophoblasts and occasionally contained medium to large trophoblasts. Trophoblasts and cytotrophoblasts were positive for pancytokeratin and cytokeratin 8/18, negative for alpha-fetoprotein, and contained intracytoplasmic Periodic acid-Schiff (PAS)-positive glycogen in all 4 tumors. In species with hemochorial placentation, migration of trophoblasts into maternal circulation with embolization to distant nonreproductive tissues occurs and may explain the unusual subcutaneous distribution of these 4 tumors. The 2 multiloculated paucicellular tumors may represent an early stage of neoplastic transformation. To the authors' knowledge, this is the first report characterizing choriocarcinomas in extrareproductive sites in rodents.

自发性绒毛膜癌是一种罕见的、高度血管化的恶性滋养层肿瘤,发生在人类和动物身上。本报告描述了来自圈养繁殖群体的4只多胎但未受精的Amargosa田鼠(加利福尼亚田鼠)皮下组织中4例绒毛膜癌的异常自发表现。两个皮下肿瘤由纤维血管间质内的中大型滋养层和细胞滋养层的多灶性脱粘和浸润性聚集体组成。新生细胞与大小不等的血栓以及出血和坏死的空洞区有关。两个皮下肿瘤主要由膨胀的、充满血液的囊性空间组成,由肿瘤细胞滋养层排列,偶尔含有中到大的滋养层。在所有4个肿瘤中,滋养层和细胞滋养层均为泛细胞角蛋白和细胞角蛋白8/18阳性,甲胎蛋白阴性,并含有细胞质内周期酸席夫(PAS)阳性糖原。在有血绒毛胎盘形成的物种中,滋养层细胞迁移到母体循环中,并栓塞到远处的非生殖组织,这可能解释了这4种肿瘤不寻常的皮下分布。2个多房性少细胞肿瘤可能代表肿瘤转化的早期阶段。据作者所知,这是第一份描述啮齿类动物生殖外部位绒毛膜癌的报告。
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引用次数: 0
Melan-A immunolabeling in canine extramedullary plasmacytomas 犬髓外浆细胞瘤中的 Melan-A 免疫标记
IF 2.4 2区 农林科学 Q2 PATHOLOGY Pub Date : 2024-04-20 DOI: 10.1177/03009858241246979
Lukas Schuwerk, Anastasiia Ulianytska, Wolfgang Baumgärtner, Wencke Reineking
Histologic diagnosis of less well-differentiated cases of canine extramedullary plasmacytomas (CEMPs) may require immunohistochemical confirmation to discriminate these tumors from other round cells tumors including lymphoma, cutaneous histiocytoma, and amelanotic melanomas. CEMPs are characterized by widespread immunoreactivity for multiple myeloma 1 (MUM1) antigen and λ light chains, while the melanocytic marker melan-A has been reported to yield negative results. Here, 33 randomly selected CEMPs, 20 melanocytomas, and 20 malignant melanomas were immunohistochemically tested for MUM1, melan-A, and PNL2. In addition, CEMPs were examined for PAX5, E-cadherin, CD3, CD18, CD20, S100, as well as λ and κ light chain immunoreactivity. All CEMPs were characterized by labeling for MUM1 and λ light chain, as well as variable immunopositivity for the remaining antibodies. Notably, 13 cases of CEMPs (39.4%) exhibited immunolabeling for melan-A. Melanocytic tumors immunolabeled for melan-A (40/40; 100%) and PNL2 (34/40; 85%). An unexpected cytoplasmic immunoreactivity for MUM1 was observed in 2 melanocytic tumors. Summarized, MUM1 or melan-A immunomarkers alone are not sufficient to differentiate between CEMPs and amelanotic melanomas and should be part of a larger immunopanel including λ light chain, CD20, and PNL2.
犬髓外浆细胞瘤(CEMPs)是一种分化较差的肿瘤,其组织学诊断可能需要免疫组化确认,以便将这些肿瘤与其他圆形细胞瘤(包括淋巴瘤、皮肤组织细胞瘤和黑色素瘤)区分开来。CEMP的特点是对多发性骨髓瘤1(MUM1)抗原和λ轻链具有广泛的免疫反应性,而黑色素细胞标记物melan-A据报道会产生阴性结果。本文随机抽取了33例CEMP、20例黑色素细胞瘤和20例恶性黑色素瘤,对其进行了MUM1、melan-A和PNL2的免疫组化检测。此外,还对 CEMP 进行了 PAX5、E-钙粘蛋白、CD3、CD18、CD20、S100 以及 λ 和 κ 轻链免疫反应的检测。所有 CEMP 的特征都是标记了 MUM1 和 λ 轻链,其余抗体也有不同程度的免疫阳性。值得注意的是,13 例 CEMP(39.4%)表现出黑色素-A 的免疫标记。黑色素细胞肿瘤对黑色素-A(40/40;100%)和PNL2(34/40;85%)免疫标记。在 2 个黑色素细胞肿瘤中意外观察到了 MUM1 的细胞质免疫反应。综上所述,MUM1或melan-A免疫标记物本身不足以区分CEMPs和黑色素瘤,而应作为包括λ轻链、CD20和PNL2在内的更大免疫列表的一部分。
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引用次数: 0
Tissue and cellular tropism of Eptesicus fuscus gammaherpesvirus in big brown bats, potential role of pulmonary intravascular macrophages 大棕蝠组织和细胞中的大棕蝠γ疱疹病毒滋养特性,肺血管内巨噬细胞的潜在作用
IF 2.4 2区 农林科学 Q2 PATHOLOGY Pub Date : 2024-04-15 DOI: 10.1177/03009858241244849
Ursula G. Perdrizet, Janet E. Hill, LaRhonda Sobchishin, Baljit Singh, Champika Fernando, Trent K. Bollinger, Vikram Misra
Gammaherpesviruses (γHVs) are recognized as important pathogens in humans but their relationship with other animal hosts, especially wildlife species, is less well characterized. Our objectives were to examine natural Eptesicus fuscus gammaherpesvirus (EfHV) infections in their host, the big brown bat ( Eptesicus fuscus), and determine whether infection is associated with disease. In tissue samples from 132 individual big brown bats, EfHV DNA was detected by polymerase chain reaction in 41 bats. Tissues from 59 of these cases, including 17 from bats with detectable EfHV genomes, were analyzed. An EfHV isolate was obtained from one of the cases, and electron micrographs and whole genome sequencing were used to confirm that this was a unique isolate of EfHV. Although several bats exhibited various lesions, we did not establish EfHV infection as a cause. Latent infection, defined as RNAScope probe binding to viral latency-associated nuclear antigen in the absence of viral envelope glycoprotein probe binding, was found within cells of the lymphoid tissues. These cells also had colocalization of the B-cell probe targeting CD20 mRNA. Probe binding for both latency-associated nuclear antigen and a viral glycoprotein was observed in individual cells dispersed throughout the alveolar capillaries of the lung, which had characteristics of pulmonary intravascular macrophages. Cells with a similar distribution in bat lungs expressed major histocompatibility class II, a marker for antigen presenting cells, and the existence of pulmonary intravascular macrophages in bats was confirmed with transmission electron microscopy. The importance of this cell type in γHVs infections warrants further investigation.
γ疱疹病毒(γHVs)被认为是人类的重要病原体,但它们与其他动物宿主(尤其是野生动物物种)之间的关系却不太清楚。我们的目的是研究大棕蝠宿主中的天然大棕蝠γ疱疹病毒(EfHV)感染情况,并确定感染是否与疾病相关。在 132 只大棕蝠的组织样本中,有 41 只蝙蝠通过聚合酶链反应检测到了 EfHV DNA。对其中 59 例蝙蝠的组织进行了分析,包括 17 例检测到 EfHV 基因组的蝙蝠。从其中一个病例中获得了一个 EfHV 分离物,并通过电子显微照片和全基因组测序确认这是一个独特的 EfHV 分离物。虽然有几只蝙蝠出现了各种病变,但我们并未确定 EfHV 感染是病因之一。在淋巴组织细胞内发现了潜伏感染,即在没有病毒包膜糖蛋白探针结合的情况下,RNAScope探针与病毒潜伏相关核抗原结合。这些细胞还与靶向 CD20 mRNA 的 B 细胞探针共定位。在散布于肺泡毛细血管中的单个细胞中观察到了潜伏期相关核抗原和病毒糖蛋白的探针结合,这些细胞具有肺血管内巨噬细胞的特征。在蝙蝠肺中有类似分布的细胞表达主要组织相容性II类,这是抗原呈递细胞的标记,透射电子显微镜证实了蝙蝠肺血管内巨噬细胞的存在。这种细胞类型在γHVs感染中的重要性值得进一步研究。
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引用次数: 0
ORF virus causes tumor-promoting inflammation in sheep and goats ORF 病毒导致绵羊和山羊出现肿瘤促进炎症
IF 2.4 2区 农林科学 Q2 PATHOLOGY Pub Date : 2024-04-13 DOI: 10.1177/03009858241241794
Davide Pintus, Maria G. Cancedda, Giantonella Puggioni, Rosario Scivoli, Angela M. Rocchigiani, Caterina Maestrale, Elisabetta Coradduzza, Roberto Bechere, Luciana Silva-Flannery, Hannah A. Bullock, Simona Macciocu, Maria A. Montesu, Vincenzo Marras, Simone Dore, Jana M. Ritter, Ciriaco Ligios
ORF virus (ORFV) causes contagious ecthyma (“ORF”), a disease of sheep and goats characterized by lesions ranging from vesicles and pustules to atypical papilloma-like and angiomatous lesions in the skin and mucosae. The authors investigated the molecular factors leading to the ORF-associated atypical tumor-like changes. Fifteen lambs, 15 kids, and an adult ram clinically affected by natural ORFV infection were enrolled in the study and examined by several methods. ORFV was detected by viral culture or real-time polymerase chain reaction (RT-PCR) in the lesioned tissues and in the blood of the clinically affected sheep and goats. Surprisingly, ORFV was also detected in the blood of healthy goats from an affected herd. Microscopically, they found a pseudo-papillomatous proliferation of the epithelium, while the dermis and lamina propria were expanded by a proliferating neovascular component that highly expressed the viral vascular endothelial growth factor (vVEGF) and its host receptor vascular endothelial growth factor receptor 2 (VEGFR2). Immunohistochemistry, immunofluorescence, and in situ hybridization for mRNA showed that epidermal growth factor receptor (EGFR) was expressed in the fibrovascular component, in the infiltrating CD163+ macrophages, and in the basal stratum of the epidermis. Confocal immunofluorescence microscopy demonstrated that CD163+ macrophages were associated with VEGF and VEGFR2. Finally, they found by quantitative RT-PCR the overexpression of the interleukin-6 and VEGFR2 genes in the lesioned tissues. These findings suggest that ORFV activates an inflammatory reaction characterized by CD163+ macrophages expressing EGFR and VEGFR2, which might play an oncogenic role through synergistic action with vVEGF signaling.
ORF病毒(ORFV)会引起绵羊和山羊的传染性外皮炎("ORF"),这种疾病的特征是皮肤和粘膜出现从水泡和脓疱到非典型乳头状瘤样病变和血管瘤样病变的各种病变。作者研究了导致 ORF 相关非典型肿瘤样病变的分子因素。15 只羔羊、15 只小羊和一只成年公羊在临床上受到 ORFV 自然感染的影响。通过病毒培养或实时聚合酶链反应(RT-PCR)在病变组织和临床感染绵羊和山羊的血液中检测到 ORFV。令人惊讶的是,在疫区健康山羊的血液中也检测到了 ORFV。在显微镜下,他们发现上皮有假乳头状增生,而真皮和固有层被增生的新生血管成分扩大,新生血管成分高度表达病毒性血管内皮生长因子(vVEGF)及其宿主受体血管内皮生长因子受体 2(VEGFR2)。免疫组化、免疫荧光和 mRNA 原位杂交显示,表皮生长因子受体(EGFR)在纤维血管成分、浸润的 CD163+ 巨噬细胞和表皮基底层中均有表达。共焦免疫荧光显微镜显示,CD163+巨噬细胞与血管内皮生长因子和血管内皮生长因子受体2相关。最后,他们通过定量 RT-PCR 发现白细胞介素-6 和 VEGFR2 基因在病变组织中过度表达。这些发现表明,ORFV 激活了以表达表皮生长因子受体(EGFR)和血管内皮生长因子受体(VEGFR)2 的 CD163+ 巨噬细胞为特征的炎症反应,这可能通过与 VEGF 信号的协同作用发挥致癌作用。
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引用次数: 0
SOX-10 and TRP-1 expression in feline ocular and nonocular melanomas 猫眼部和非眼部黑色素瘤中的 SOX-10 和 TRP-1 表达
IF 2.4 2区 农林科学 Q2 PATHOLOGY Pub Date : 2024-04-13 DOI: 10.1177/03009858241244850
Margherita Orlandi, Ilaria Porcellato, Monica Sforna, Adriana Lo Giudice, Giuseppe Giglia, Luca Mechelli, Chiara Brachelente
In felines, ocular and nonocular melanomas are uncommon tumors that represent a diagnostic challenge for pathologists, especially when amelanotic. To date, the immunohistochemical diagnostic panel in cats is based on specific melanocytic markers (Melan-A and PNL2) and a nonspecific but sensitive marker (S100). In human medicine, SOX-10 is reported to be a sensitive antibody for the detection of melanoma micrometastasis in the lymph node. TRP-1, an enzyme involved in melanogenesis, has recently been used in humans and dogs as a specific melanocyte marker. The aim of this study was to evaluate the cross-reactivity and the expression of SOX-10 and TRP-1 antibodies in feline normal tissue and melanocytic tumors. Thirty-one cases of ocular, cutaneous, and oral melanomas were retrospectively evaluated and confirmed by histopathological examination and by immunolabeling with Melan-A and/or PNL2. SOX-10 nuclear expression in normal tissues was localized in epidermal, subepidermal, hair bulb, and iridal stromal melanocytes and dermal nerves. In melanomas, nuclear expression of SOX-10 was detected in ocular (11/12; 92%), oral (6/7; 86%), and cutaneous sites (12/12; 100%). TRP-1 cytoplasmic immunolabeling in normal tissue was observed in epidermal and bulbar melanocytes and in the lining pigmented epithelium of the iris and in its stroma. Its expression was positively correlated to the degree of pigmentation in the tumor and was observed in 75% of ocular (9/12), 43% of oral (3/7), and 33% of cutaneous melanomas (4/12). This study demonstrated the cross-reactivity of SOX-10 and TRP-1 antibodies in feline non-neoplastic melanocytes and their expression in ocular and nonocular melanomas.
在猫科动物中,眼部和非眼部黑色素瘤是一种不常见的肿瘤,对病理学家来说是一种诊断难题,尤其是当黑色素瘤出现时。迄今为止,猫的免疫组化诊断方法主要基于特异性黑色素细胞标记物(Melan-A 和 PNL2)和一种非特异性但敏感的标记物(S100)。据报道,在人类医学中,SOX-10 是检测淋巴结中黑色素瘤微转移的敏感抗体。TRP-1是一种参与黑色素生成的酶,最近在人类和狗身上被用作特异性黑色素细胞标记物。本研究旨在评估猫正常组织和黑色素细胞肿瘤中 SOX-10 和 TRP-1 抗体的交叉反应和表达情况。研究人员对31例眼部、皮肤和口腔黑色素瘤进行了回顾性评估,并通过组织病理学检查和Melan-A和/或PNL2免疫标记进行了确认。在正常组织中,SOX-10的核表达定位于表皮、表皮下、毛球和虹膜基质黑素细胞以及真皮神经。在黑色素瘤中,眼部(11/12;92%)、口腔(6/7;86%)和皮肤部位(12/12;100%)都检测到了 SOX-10 的核表达。在正常组织中,表皮和球部黑素细胞、虹膜内膜色素上皮及其基质中均可观察到 TRP-1 细胞质免疫标记。它的表达与肿瘤的色素沉着程度呈正相关,在 75% 的眼部黑色素瘤(9/12 例)、43% 的口腔黑色素瘤(3/7 例)和 33% 的皮肤黑色素瘤(4/12 例)中均可观察到。这项研究证明了SOX-10和TRP-1抗体在猫非肿瘤性黑色素细胞中的交叉反应性,以及它们在眼部和非眼部黑色素瘤中的表达。
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Veterinary Pathology
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