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CRP Versus SAA for Identification of Inflammatory Hepatic Adenomas. CRP与SAA在炎症性肝腺瘤鉴别中的比较。
IF 1.6 4区 医学 Q2 Health Professions Pub Date : 2023-10-01 Epub Date: 2023-09-13 DOI: 10.1097/PAI.0000000000001155
Gwyneth S T Soon, Saba Yasir, Dhanpat Jain, Sanjay Kakar, Tsung-Teh Wu, Matthew M Yeh, Michael S Torbenson, Zongming Eric Chen

Subtyping hepatic adenomas is important for patient management due to differing complication risks. Immunohistochemical staining with C-reactive protein (CRP) and serum amyloid-A (SAA) is widely accepted as a surrogate for molecular classification to identify inflammatory hepatocellular adenomas. Limited data, however, has been published on how these 2 stains compare for sensitivity. We conducted a large, multicenter, retrospective study to examine the sensitivity and staining characteristics of CRP and SAA in inflammatory hepatic adenomas, with focal nodular hyperplasia (FNHs) as a control group. Inflammatory adenomas were identified in 133 patients (average age 37 years, 109 were female). In all, 69.9% of cases were resection specimens and 90.2% of all cases showed positive staining for both CRP and SAA; 10 (7.5%) were positive for CRP only and 3 (2.3%) were positive for SAA only. CRP was more sensitive than SAA (97.74% vs. 92.48%, P -value = 0.0961) and showed more extensive and intense staining, with a significantly higher modified H-score ( P <0.001). Focal nodular hyperplasia can also show positive CRP and SAA staining but with a lower modified H-score ( P <0.0001). Based on beta-catenin and glutamine synthetase staining, 26 of inflammatory adenomas also had beta-catenin activation (19.5%). All 3 cases with positive SAA and negative CRP staining were beta-catenin activated. In contrast, the proportion of cases that were CRP positive and SAA negative was similar regardless of beta-catenin activation. The data affirms the strategy of using both CRP and SAA immunostains for hepatic adenoma subtyping and raises the awareness of the highly variable nature of SAA staining characteristics.

由于并发症风险不同,肝腺瘤亚型对患者管理很重要。C反应蛋白(CRP)和血清淀粉样蛋白-A(SAA)的免疫组织化学染色被广泛接受为识别炎症性肝细胞腺瘤的分子分类的替代品。然而,关于这两种污渍的敏感性比较数据有限。我们进行了一项大型、多中心、回顾性研究,以局灶性结节性增生(FNHs)为对照组,检查炎症性肝腺瘤中CRP和SAA的敏感性和染色特征。在133名患者中发现了炎症性腺瘤(平均年龄37岁,109人为女性)。总的来说,69.9%的病例是切除标本,90.2%的病例显示CRP和SAA阳性;10例(7.5%)仅CRP阳性,3例(2.3%)仅SAA阳性。CRP比SAA更敏感(97.74%对92.48%,P值=0.0961),并且显示出更广泛和更强烈的染色,具有显著更高的修饰H核(P
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引用次数: 0
Impact of Prolonged Ischemia on the Immunohistochemical Expression of Programmed Death Ligand 1 (PD-L1). 长时间缺血对程序性死亡配体1(PD-L1)免疫组织化学表达的影响。
IF 1.6 4区 医学 Q2 Health Professions Pub Date : 2023-10-01 Epub Date: 2023-09-05 DOI: 10.1097/PAI.0000000000001153
Angels Barberà, Juan González, Montserrat Martin, Jose L Mate, Albert Oriol, Fina Martínez-Soler, Tomas Santalucia, Pedro Luis Fernández

Antibodies targeting programmed death receptor 1 or programmed death ligand 1 (PD-L1) have become a standard of care to treat different cancers; for some of these tumors, there is a correlation between tissue expression of PD-L1 and response rates in patients. Although most of the analytical challenges in the evaluation of PD-L1 expression have been standardized, preanalytical issues have been less explored. The objective of this study was to evaluate the impact of time of ischemia on the performance of 2 commonly used antibodies against PD-L1. Sixteen tonsillectomy samples were kept in ischemia for <30 minutes from sample obtention (control) and 1, 3, 6, 12, and 24 hours at room temperature before formalin fixation and paraffin embedding. Selected areas were inserted into TMA paraffin recipient blocks stained with SP142 and SP263 antibodies and evaluated by 2 blind observers. The proportion of suboptimally stained samples was significantly higher for samples with cold ischemia times 6 hours or over ( P <0.0001). False-negative results were 25% in samples exposed to 6 hours of ischemia and raised to 34% for samples remaining in ischemia for 12 or 24 hours. When all observations were pooled, SP142 provided suboptimal results in 24% of observations and SP263 in 12.5%; this is a statistically significant difference ( P =0.042). In conclusion, the quality of staining for PD-L1 in tonsil samples varies with the time of cold ischemia. The SP142 antibody presented a significantly lower tolerance to prolonged cold ischemia than SP263. These results reveal the relevance of controlled preanalytical processing of samples.

靶向程序性死亡受体1或程序性死亡配体1(PD-L1)的抗体已成为治疗不同癌症的护理标准;对于其中一些肿瘤,PD-L1的组织表达与患者的反应率之间存在相关性。尽管PD-L1表达评估中的大多数分析挑战已经标准化,但对分析前问题的探索较少。本研究的目的是评估缺血时间对2种常用抗PD-L1抗体性能的影响。16个扁桃体切除术样本在缺血状态下保存
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引用次数: 0
Vascular Expression of Prostate-specific Membrane Antigen (PSMA) in MiTF Family Translocation Renal Cell Carcinoma and Related Neoplasms. 前列腺特异性膜抗原(PSMA)在MiTF家族易位肾细胞癌及相关肿瘤中的血管表达。
IF 1.6 4区 医学 Q2 Health Professions Pub Date : 2023-09-01 Epub Date: 2023-07-20 DOI: 10.1097/PAI.0000000000001142
Ezra G Baraban, Yasser Ged, Nirmish Singla, Mohammad E Allaf, Michael A Gorin, Mark C Markowski, Steven P Rowe, Pedram Argani

Multiple studies have demonstrated prostate-specific membrane antigen (PSMA) expression in the neo-vasculature of non-prostate tumors including clear cell renal cell carcinoma (ccRCC). However, PSMA expression in rare renal tumors including MiTF family translocation renal cell carcinoma has not been previously characterized. We examined PSMA expression by immunohistochemistry in a series of MiTF family translocation renal cell carcinomas as well as in several genetically related tumors including alveolar soft part sarcoma and PEComas with TFE3 rearrangements. PSMA expression was also studied in several cases of ccRCC and papillary RCC. Overall, PSMA immunohistochemistry was performed in 61 samples from 58 patients. Vascular PSMA expression was seen with the highest frequency in ccRCC [88% (14/16)] (38% focal, 50% diffuse). Translocation RCC (tRCC) demonstrated the second highest frequency of PSMA expression [71% (22/28)] (57% focal, 14% diffuse), followed by alveolar soft part sarcoma [50% (4/8)] (38% focal, 12% diffuse). No PSMA expression was seen in PEComas with TFE3 rearrangement (0/3) or papillary RCC (0/6). PSMA expression was only present in tumor-associated neo-vasculature. A patient with oligometastatic tRCC underwent 68 Ga-PSMA-11 PET imaging which detected multiple putative metastatic lesions not detected on conventional computed tomography imaging performed 2 weeks prior, supporting the potential utility of PSMA imaging in tRCC. These findings have potential implications for the utility of PSMA guided diagnostic and therapeutic agents in both common and uncommon renal cell carcinoma subtypes as well as genetically related mesenchymal neoplasms.

多项研究表明,前列腺特异性膜抗原(PSMA)在包括透明细胞肾细胞癌(ccRCC)在内的非前列腺肿瘤的新血管系统中表达。然而,PSMA在包括MiTF家族易位肾细胞癌在内的罕见肾肿瘤中的表达先前尚未得到表征。我们通过免疫组织化学检测了PSMA在一系列MiTF家族易位肾细胞癌以及几种遗传相关肿瘤中的表达,包括肺泡软部肉瘤和具有TFE3重排的PEComas。还研究了PSMA在几个ccRCC和乳头状RCC中的表达。总体而言,对58名患者的61份样本进行了PSMA免疫组织化学检查。血管PSMA表达在ccRCC中最高[88%(14/16)](38%为局灶性,50%为弥漫性)。移位性RCC(tRCC)的PSMA表达频率位居第二[71%(22/28)](57%为局灶性,14%为弥漫性),其次是肺泡软部肉瘤[50%(4/8)](38%为局灶,12%为弥漫性。在TFE3重排的PEComas(0/3)或乳头状RCC(0/6)中未发现PSMA表达。PSMA仅在肿瘤相关的新血管系统中表达。一名低转移性tRCC患者接受了68 Ga-PSMA-11 PET成像,该成像检测到了2周前常规计算机断层扫描成像未检测到的多个假定转移性病变,支持PSMA成像在tRCC中的潜在用途。这些发现对PSMA指导的诊断和治疗剂在常见和不常见肾细胞癌亚型以及遗传相关间充质肿瘤中的应用具有潜在意义。
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引用次数: 0
Renal Glomerular Expression of WT-1, TGF-β, VEGF, and ET-1 Immunostains in Murine Models of Focal and Segmental Glomerulosclerosis. 肾肾小球WT-1、TGF-β、VEGF和ET-1在局灶性和节段性肾小球硬化症小鼠模型中的表达。
IF 1.6 4区 医学 Q2 Health Professions Pub Date : 2023-09-01 Epub Date: 2023-08-03 DOI: 10.1097/PAI.0000000000001146
Sufia Husain

Primary focal segmental glomerulosclerosis (FSGS) is a type of chronic renal disease that commonly progresses to renal failure as the treatments are not particularly effective. Glomerular podocyte injury and loss are pivotal to the pathogenesis of FSGS. This study aims to explore the glomerular immunohistochemistry stain expression of Wilms tumor-1 (WT-1) (podocyte-specific protein), transforming growth factor beta (TGF-β) (cytokine protein), vascular endothelial growth factor (VEGF) (angiogenic protein), and endothelin-1 (ET-1) (profibrotic growth factor), in rats with adriamycin nephropathy, which represents the murine model of human FSGS. By the end of 8 and 12 weeks, the kidneys of adriamycin-treated rats and control rats were harvested and the histomorphology was studied. Both 8- and 12-week test groups developed proteinuria, and hypoalbuminemia and showed FSGS on hematoxylin and eosin-stained slides. The renal tissue samples were also treated with immunostains for WT-1, TGF-β, VEGF, and ET-1. The glomeruli in all the FSGS kidneys showed loss of WT-1 expression with a concomitant notable increased expression of TGF-β, VEGF, and ET-1 immunostains. These results demonstrate that as FSGS evolves, the WT-1-expressing podocytes are lost and it correlates inversely with the overexpression of TGF-β, VEGF, and ET-1, suggesting that during the pathogenesis of FSGS, podocyte damage triggers the activation of these proteins. The findings in the current study echo the theory hypothesized in world literature that TGF-β, VEGF, and ET-1 play an integral part in the evolution of FSGS. More research is needed to further detail the pathogenic role of these proteins as it may open routes to more targeted and effective treatment modalities.

原发性局灶节段性肾小球硬化症(FSGS)是一种慢性肾脏疾病,由于治疗效果不佳,通常会发展为肾衰竭。肾小球足细胞损伤和丢失是FSGS发病机制的关键。本研究旨在探讨肾母细胞瘤1(WT-1)(足细胞特异性蛋白)、转化生长因子β(TGF-β)(细胞因子蛋白)、血管内皮生长因子(VEGF)(血管生成蛋白)和内皮素-1(ET-1)(促纤维化生长因子)在阿霉素肾病大鼠肾小球中的免疫组织化学染色表达,这是人类FSGS的小鼠模型。在8周和12周结束时,收获阿霉素处理的大鼠和对照大鼠的肾脏,并研究其组织形态学。8周和12周的试验组均出现蛋白尿和低蛋白血症,苏木精和伊红染色的载玻片显示FSGS。肾组织样本也用WT-1、TGF-β、VEGF和ET-1的免疫染色处理。所有FSGS肾脏的肾小球显示WT-1表达缺失,同时TGF-β、VEGF和ET-1免疫染色的表达显著增加。这些结果表明,随着FSGS的进化,表达WT-1的足细胞丢失,并且与TGF-β、VEGF和ET-1的过度表达呈负相关,这表明在FSGS的发病机制中,足细胞损伤触发了这些蛋白质的激活。目前的研究结果与世界文献中假设的理论相呼应,即TGF-β、VEGF和ET-1在FSGS的进化中起着不可或缺的作用。需要更多的研究来进一步详细说明这些蛋白质的致病作用,因为它可能为更具针对性和有效的治疗模式开辟途径。
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引用次数: 0
Heterogeneity of the Tumor Microenvironment Across Molecular Subtypes of Breast Cancer. 癌症分子亚型肿瘤微环境的异质性。
IF 1.6 4区 医学 Q2 Health Professions Pub Date : 2023-09-01 Epub Date: 2023-06-26 DOI: 10.1097/PAI.0000000000001139
Dharambir Kashyap, Amanjit Bal, Santosh Irinike, Siddhant Khare, Shalmoli Bhattacharya, Ashim Das, Gurpreet Singh

Breast cancer is a heterogenous disease at the molecular level thus, it can be hypothesized that different molecular subtypes differ in their tumor microenvironment (TME) also. Understanding the TME heterogeneity may provide new prognostic biomarkers and new targets for cancer therapy. For deciphering heterogeneity in the TME, immunohistochemistry for immune markers (CD3, CD4, CD8, CD68, CD163, and programmed death-ligand 1), Cancer-associated fibroblast markers [anti-fibroblast activating protein α (FAP-α), platelet-derived growth factor receptor α (PDGFR-α), S100A4, Neuron-glial antigen 2, and Caveolin-1], and angiogenesis (CD31) was performed on tissue microarrays of different molecular subtypes of breast cancer. High CD3 + T cells were noted in the Luminal B subtype ( P =0.002) of which the majority were CD8 + cytotoxic T cells. Programmed death-ligand 1 expression in immune cells was highest in the human epidermal growth factor receptor 2 (Her-2)-positive and Luminal B subtypes compared with the triple-negative breast cancer (TNBC) subtype ( P =0.003). Her-2 subtype is rich in M2 tumor-associated macrophages ( P =0.000) compared with TNBC and Luminal B subtypes. M2 immune microenvironment correlated with high tumor grade and high Ki-67. Her-2 and TNBC subtypes are rich in extracellular matrix remodeling (FAP-α, P =0.003), angiogenesis-promoting (PDGFR-α; P =0.000) and invasion markers (Neuron-glial antigen 2, P =0.000; S100A4, P =0.07) compared with Luminal subtypes. Mean Microvessel density showed an increasing trend: Luminal A>Luminal B>Her-2 positive>TNBC; however, this difference was not statistically significant. The cancer-associated fibroblasts (FAP-α, PDGFR-α, and Neuron-glial antigen 2) showed a positive correlation with lymph node metastasis in specific subtypes. Immune cells, tumor-associated macrophage, and cancer-associated fibroblast-related s tromal markers showed higher expression in Luminal B, Her-2 positive, and TNBC respectively. This differential expression of different components of TME indicates heterogeneity of the TME across molecular subtypes of breast cancer.

癌症是一种分子水平上的异质性疾病,因此,可以假设不同的分子亚型在其肿瘤微环境(TME)中也有所不同。了解TME的异质性可能为癌症治疗提供新的预后生物标志物和新的靶点。为了破解TME中的异质性,免疫标记物(CD3、CD4、CD8、CD68、CD163和程序性死亡1)、癌症相关成纤维细胞标记物[抗成纤维细胞活化蛋白α(FAP-α)、血小板衍生生长因子受体α(PDGFR-α)、S100A4、神经元胶质抗原2和Caveolin-1]的免疫组织化学,在癌症不同分子亚型的组织微阵列上进行血管生成(CD31)。在Luminal B亚型中观察到高CD3+T细胞(P=0.002),其中大多数是CD8+细胞毒性T细胞。与癌症(TNBC)三阴性亚型相比,人表皮生长因子受体2(Her-2)阳性和Luminal B亚型的免疫细胞中程序性死亡配体1表达最高(P=0.003)。与TNBC和Luminal B亚型相比Her-2亚型富含M2肿瘤相关巨噬细胞(P=0.000)。M2免疫微环境与高肿瘤分级和高Ki-67相关。与Luminal亚型相比,Her-2和TNBC亚型富含细胞外基质重塑(FAP-α,P=0.003)、血管生成促进(PDGFR-α;P=0.000)和侵袭标记物(神经元-胶质抗原2,P=0.000;S100A4,P=0.007)。平均微血管密度呈增加趋势:管腔A>管腔B>Her-2阳性>TNBC;然而,这种差异在统计学上并不显著。癌症相关成纤维细胞(FAP-α、PDGFR-α和神经元胶质抗原2)在特定亚型中与淋巴结转移呈正相关。免疫细胞、肿瘤相关巨噬细胞和癌症相关成纤维细胞相关基质标记物分别在Luminal B、Her-2阳性和TNBC中表达较高。TME不同成分的差异表达表明TME在癌症分子亚型中的异质性。
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引用次数: 0
Comparison of PD-L1 IHC 22C3 PharmDx Combined Positive Score (CPS) in Primary Versus Metastatic Nodal Squamous Cell Carcinomas of the Head and Neck: Is There a Significant Difference? PD-L1 IHC 22C3 PharmDx联合阳性评分(CPS)在头颈部原发性和转移性结节性鳞状细胞癌中的比较:有显著差异吗?
IF 1.6 4区 医学 Q2 Health Professions Pub Date : 2023-09-01 Epub Date: 2023-06-27 DOI: 10.1097/PAI.0000000000001140
Ahmet Surucu, Tieying Hou, Matthew Kuhar, Greg Durm, Hector Mesa

PD-L1 IHC 22C3 pharmDx is an FDA-approved companion test to select patients for anti-PD-L1 immunotherapy. In head and neck squamous cell carcinoma PD-L1 expression is determined using a Combined Positive Score (CPS), which evaluates expression in tumor cells and tumor-associated leukocytes. We hypothesized that in nodal metastasis, the CPS should be higher given their inherent higher proportion of leukocytes. A significant difference in CPS between sites would mean that the tissue chosen for PD-L1 testing would impact patient eligibility for therapy. Currently, guidelines about which tissue should be tested do not exist. PD-L1 22C3 IHC was performed in the primary and nodal metastases of 35 head and neck squamous cell carcinoma, and a CPS was generated by 3 pathologists. Mean CPS was higher at the primary than the nodal metastasis: 47.2 versus 42.2; however, the difference was not statistically significant: P=0.259 . By therapeutic groups: negative (CPS <1), low (CPS 1-19) and high (CPS≥20), low-expression was more common in the primary: 40 vs. 26%, and high-expression in the nodal metastasis: 74 vs. 60% but this difference was not statistically significant: P=0.180. Stratified by positive versus negative (CPS <1 vs. ≥1), there were no differences between sites. Interobserver agreement for CPS among the 3 raters was slight for both sites: ƙ = 0.117 and 0.025, fair if stratified by therapeutic group: ƙ = 0.371 and 0.318, and near perfect if stratified as negative versus positive: ƙ = 0.652 and 1. There were no statistically significant differences in CPS between primary and nodal metastases independent of how the CPS was stratified.

PD-L1 IHC 22C3 pharmDx是美国食品药品监督管理局批准的一项配套测试,用于选择患者进行抗PD-L1免疫治疗。在头颈部鳞状细胞癌中,PD-L1的表达是使用联合阳性评分(CPS)来确定的,该评分评估肿瘤细胞和肿瘤相关白细胞中的表达。我们假设,在淋巴结转移中,CPS应该更高,因为它们固有的白细胞比例更高。位点之间CPS的显著差异意味着选择用于PD-L1测试的组织将影响患者的治疗资格。目前,关于哪些组织应该接受检测的指导方针还不存在。PD-L1 22C3 IHC在35例头颈部鳞状细胞癌的原发性和淋巴结转移中进行,3名病理学家生成了CPS。原发性转移的平均CPS高于淋巴结转移:47.2比42.2;然而,差异无统计学意义:P=0.259。按治疗组分:阴性(CPS
{"title":"Comparison of PD-L1 IHC 22C3 PharmDx Combined Positive Score (CPS) in Primary Versus Metastatic Nodal Squamous Cell Carcinomas of the Head and Neck: Is There a Significant Difference?","authors":"Ahmet Surucu,&nbsp;Tieying Hou,&nbsp;Matthew Kuhar,&nbsp;Greg Durm,&nbsp;Hector Mesa","doi":"10.1097/PAI.0000000000001140","DOIUrl":"10.1097/PAI.0000000000001140","url":null,"abstract":"<p><p>PD-L1 IHC 22C3 pharmDx is an FDA-approved companion test to select patients for anti-PD-L1 immunotherapy. In head and neck squamous cell carcinoma PD-L1 expression is determined using a Combined Positive Score (CPS), which evaluates expression in tumor cells and tumor-associated leukocytes. We hypothesized that in nodal metastasis, the CPS should be higher given their inherent higher proportion of leukocytes. A significant difference in CPS between sites would mean that the tissue chosen for PD-L1 testing would impact patient eligibility for therapy. Currently, guidelines about which tissue should be tested do not exist. PD-L1 22C3 IHC was performed in the primary and nodal metastases of 35 head and neck squamous cell carcinoma, and a CPS was generated by 3 pathologists. Mean CPS was higher at the primary than the nodal metastasis: 47.2 versus 42.2; however, the difference was not statistically significant: P=0.259 . By therapeutic groups: negative (CPS <1), low (CPS 1-19) and high (CPS≥20), low-expression was more common in the primary: 40 vs. 26%, and high-expression in the nodal metastasis: 74 vs. 60% but this difference was not statistically significant: P=0.180. Stratified by positive versus negative (CPS <1 vs. ≥1), there were no differences between sites. Interobserver agreement for CPS among the 3 raters was slight for both sites: ƙ = 0.117 and 0.025, fair if stratified by therapeutic group: ƙ = 0.371 and 0.318, and near perfect if stratified as negative versus positive: ƙ = 0.652 and 1. There were no statistically significant differences in CPS between primary and nodal metastases independent of how the CPS was stratified.</p>","PeriodicalId":48952,"journal":{"name":"Applied Immunohistochemistry & Molecular Morphology","volume":null,"pages":null},"PeriodicalIF":1.6,"publicationDate":"2023-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10193314","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Immunohistochemical Surrogates for Molecular Stratification in Medulloblastoma. 髓母细胞瘤分子分层的免疫组织化学替代物。
IF 1.6 4区 医学 Q2 Health Professions Pub Date : 2023-09-01 Epub Date: 2023-07-21 DOI: 10.1097/PAI.0000000000001143
Dheeraj Chinnam, Aastha Saraswati, Swathi Jogunoori, Aanchal Verma, Tanvi Kiran, Pravin Salunke, Nalini Gupta, Narendra Kumar, Renu Madan, Bishan Dass Radotra, Kirti Gupta

Background: The WHO classification of central nervous system neoplasms (2016) recognized 4 histologic variants and genetically defined molecular subgroups within medulloblastoma (MB). Further, in the 2021 classification, new subtypes have been provisionally added within the existing subgroups reflecting the biological diversity. YAP1, GAB1, and β-catenin were conventionally accepted as surrogate markers to identify these genetic subgroups.

Objectives: We aimed to stratify MB into molecular subgroups using 3 immunohistochemical markers. TP53 mutation was also assessed in Wingless (WNT), and Sonic Hedgehog (SHH) subgroups. Demographic profiles, imaging details, and survival outcomes were compared within these molecular subgroups.

Patients and methods: Our cohort included 164 MB cases diagnosed over the last 10 years. The histologic variants were identified on histology, and tumors were molecularly stratified using YAP1, GAB1, and β-catenin. Further, TP53 mutation was assessed using immunohistochemical in WNT and SHH subgroups. The clinical details and survival outcomes were retrieved from the records, and the mentioned correlates were evaluated statistically.

Results: The age ranged from 1 to 52 years with M:F ratio of 2:1. Group 3/group 4 constituted the majority (48.4%), followed by SHH (45.9%) and WNT subgroups (5.7%). Desmoplastic/nodular and MB with extensive nodularity had the best survival, whereas large cell/anaplastic had the worst. The follow-up period ranged from 1 to 129 months. The best outcome was observed for the WNT subgroup, followed by the SHH subgroup; group 3/group 4 had the worst. Among the SHH subgroup, TP53 mutant tumors had a significantly poorer outcome compared with SHH-TP53 wildtype.

Conclusions: Molecular stratification significantly contributes to prognostication, and a panel of 3 antibodies is helpful in stratifying MB into its subgroups in centers where access to advanced molecular testing is limited. Our study reinforces the efficacy of incorporating this cost-effective, minimal panel into routine practice for stratification. Further, we propose a 3-risk stratification grouping, incorporating morphology and molecular markers.

背景:世界卫生组织中枢神经系统肿瘤分类(2016)识别了髓母细胞瘤(MB)中的4种组织学变异和遗传定义的分子亚群。此外,在2021年的分类中,在反映生物多样性的现有亚组中暂时增加了新的亚型。YAP1、GAB1和β-连环蛋白通常被认为是鉴定这些遗传亚群的替代标记。目的:我们旨在使用3种免疫组织化学标记物将MB分为分子亚组。TP53突变也在Wingless(WNT)和Sonic Hedgehog(SHH)亚组中进行了评估。在这些分子亚组中比较人口统计学特征、影像学细节和生存结果。患者和方法:我们的队列包括过去10年中诊断的164例MB病例。在组织学上鉴定组织学变异,并使用YAP1、GAB1和β-连环蛋白对肿瘤进行分子分层。此外,在WNT和SHH亚组中使用免疫组织化学评估TP53突变。从记录中检索临床细节和生存结果,并对上述相关性进行统计学评估。结果:患者年龄1~52岁,男女比例为2:1。第3组/第4组占大多数(48.4%),其次是SHH(45.9%)和WNT亚组(5.7%)。结节性/结节性和广泛结节性MB的存活率最高,而大细胞/间变性的存活率最差。随访时间为1-129个月。WNT亚组的疗效最好,其次是SHH亚组;第3组/第4组最差。在SHH亚组中,与SHH-TP53野生型相比,TP53突变型肿瘤的预后明显较差。结论:分子分层有助于预测,在先进分子检测有限的中心,一组3种抗体有助于将MB分为其亚组。我们的研究加强了将这种成本效益高、最小的小组纳入常规分层实践的有效性。此外,我们提出了一个3风险分层分组,结合形态学和分子标记。
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引用次数: 0
Expression and Significance of MTA2 and CPNE1 in Cervical Squamous Cell Carcinoma. MTA2和CPNE1在宫颈鳞状细胞癌中的表达及意义。
IF 1.6 4区 医学 Q2 Health Professions Pub Date : 2023-09-01 Epub Date: 2023-07-03 DOI: 10.1097/PAI.0000000000001138
Lixin Wang, Gang Chen, Chen Zhou, Chao Wu, Jingui Jiang

The aim of this study was to investigate the expression and clinical significance of MTA2 and CPNE1 proteins in cervical squamous cell carcinoma. In this study, high-risk human papillomavirus (HPV) typing was performed on cervical cancer tissues. Reverse transcription polymerase chain reaction and immunochemical EliVision method were used to examine the expressions of MTA2 and CPNE1 in the cervix, and their relationship with clinicopathologic features. We found that it is mainly distributed in these types, namely HPV-16 (23.8%), HPV-18 (20.9%), HPV-53 (17.1%), HPV-52 (15.5%), HPV-82 (11.7%), HPV-56 (10.8%). The expressions of MTA2 and CPNE1 in cervical squamous cell carcinoma tissues were significantly higher than those in normal tissues ( P <0.01). The expressions of MTA2 and CPNE1 were correlated with FIGO stage, degree of differentiation, and lymph node metastasis of cervical cancer ( P <0.05), but not with the patient's age ( P >0.05). The rank correlation coefficient of MTA2 and CPNE1 protein expression in cervical squamous cell carcinoma was 0.668 ( P <0.01), and the 2 expressions were positively correlated. MTA2 and CPNE1 are closely related to the occurrence and development of cervical squamous cell carcinoma and may play a synergistic role in the evolution of cervical squamous cell carcinoma.

本研究旨在探讨MTA2和CPNE1蛋白在宫颈鳞状细胞癌中的表达及其临床意义。本研究对癌症宫颈组织进行高危型人乳头瘤病毒(HPV)分型。采用逆转录聚合酶链反应和免疫化学EliVision方法检测MTA2和CPNE1在宫颈中的表达及其与临床病理特征的关系。我们发现它主要分布在这些类型中,即HPV-16(23.8%)、HPV-18(20.9%)、HPV-53(17.1%)、HPV-52(15.5%)、,HPV-56(10.8%),MTA2和CPNE1在宫颈鳞状细胞癌组织中的表达明显高于正常组织(P<0.05),MTA2/CPNE1在宫颈鳞癌中的表达等级相关系数为0.668(P<0.01)
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引用次数: 0
HER2 Equivocal (Score = 2+) Breast Carcinoma Cases Identified by Immunohistochemistry at a South African Hospital. What is the Impact of Fluorescent In Situ Hybridization Testing? 南非一家医院通过免疫组织化学鉴定的HER2等位(得分=2+)乳腺癌病例。荧光原位杂交检测的影响是什么?
IF 1.6 4区 医学 Q2 Health Professions Pub Date : 2023-09-01 Epub Date: 2023-07-06 DOI: 10.1097/PAI.0000000000001141
Reena Dhansukh Mohanlal, Nikki Bouwer, Pascale Willem

The American Society of Clinical Oncology and the College of American Pathologists (ASCO/CAP) guidelines are used for human epidermal growth factor receptor 2 (HER2) reporting in breast carcinoma. Cases that demonstrate weak to moderate complete membrane immunohistochemical staining in >10% of the tumor are scored as 2+ (equivocal). This study aimed to determine what proportion of HER2 immunohistochemistry (IHC) score = 2+ breast carcinomas were confirmed to be positive by HER2 fluorescent in situ hybridization (FISH). There were 241 HER2 IHC score = 2+ breast carcinomas included. Most (74.3%) carcinomas were estrogen and progesterone receptor-positive. Invasive breast carcinoma of no special type (89.2%) was the commonest histologic subtype. Most tumors were grade 2 (64.3%). As per the FISH report, at the time of diagnosis, 27 cases (11.2%) were HER2 FISH positive. All HER2 FISH equivocal cases and one FISH positive case assessed using the 2013 ASCO/CAP HER2 criteria were reclassified to HER2 FISH negative when the 2018 criteria were applied. There was a high level of agreement (κ = 0.979) between HER2 FISH results obtained using the 2013 and the 2018 criteria. This study provides insight into the frequency of HER2 FISH positivity (11.2%) among HER2 IHC score = 2+ breast carcinomas and the impact of modifications to the ASCO/CAP HER2 guidelines. Elimination of the HER2 FISH equivocal category by the 2018 guidelines has reduced the need for repeat testing and simplified clinical management. Reclassification of previous HER2 FISH positive to negative has resulted in some patients being ineligible for costly anti-HER therapy.

美国临床肿瘤学会和美国病理学家学会(ASCO/CAP)指南用于乳腺癌中人类表皮生长因子受体2(HER2)的报告。在>10%的肿瘤中表现出弱至中度完全膜免疫组织化学染色的病例被评分为2+(模棱两可)。本研究旨在确定HER2免疫组织化学(IHC)评分=2+乳腺癌通过HER2荧光原位杂交(FISH)确认为阳性的比例。包括241例HER2 IHC评分=2+乳腺癌。大多数(74.3%)癌是雌激素和孕激素受体阳性。无特殊类型的侵袭性乳腺癌(89.2%)是最常见的组织学亚型。大多数肿瘤为2级(64.3%)。根据FISH报告,在诊断时,有27例(11.2%)HER2 FISH阳性。当应用2018年标准时,使用2013年ASCO/CAP HER2标准评估的所有HER2 FISH模棱两可的病例和一例FISH阳性病例被重新分类为HER2 FISH-阴性。使用2013年和2018年标准获得的HER2 FISH结果之间存在高度一致性(κ=0.799)。本研究深入了解了HER2 IHC评分=2+乳腺癌中HER2 FISH阳性率(11.2%)以及ASCO/CAP HER2指南修改的影响。2018年指南消除了HER2 FISH模棱两可的类别,减少了重复检测的需要,简化了临床管理。先前HER2 FISH阳性至阴性的重新分类导致一些患者没有资格接受昂贵的抗HER治疗。
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引用次数: 0
Toward a Total Dataization of Anatomic Pathology: Are You Ready? 实现解剖病理学的全面数据化:您准备好了吗?
IF 1.6 4区 医学 Q2 Health Professions Pub Date : 2023-09-01 Epub Date: 2023-07-27 DOI: 10.1097/PAI.0000000000001145
Pierre-Olivier Fiset, Gilbert Bigras
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引用次数: 0
期刊
Applied Immunohistochemistry & Molecular Morphology
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