Lydia L Wu, S. Shen, Henry Biermann, M. Nelson, N. Bagrodia, Ann M Defnet, Rebecca Kirschner, Peter Hahn, Tzintzuni I. Garcia, F. Flores-Guzmán, Jessica J Kandel, Henar Cuervo, Sonia L Hernandez
{"title":"The long and winding road: detecting and quantifying Notch activation in endothelial cells","authors":"Lydia L Wu, S. Shen, Henry Biermann, M. Nelson, N. Bagrodia, Ann M Defnet, Rebecca Kirschner, Peter Hahn, Tzintzuni I. Garcia, F. Flores-Guzmán, Jessica J Kandel, Henar Cuervo, Sonia L Hernandez","doi":"10.24238/13221-13-1-201","DOIUrl":"https://doi.org/10.24238/13221-13-1-201","url":null,"abstract":"","PeriodicalId":23948,"journal":{"name":"Vascular Cell","volume":"1 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2021-12-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"45431731","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
E. Rezaie, N. Visser, R. Thaler, F. Khani, P. Friedrich, A. Folpe, D. Deyle, A. Shin, A. J. Wijnen, A. Bishop
Background: Cryopreserved bone allografts are often used to reconstruct segmental bone defects. They are non-viable, which can result in infection, non-union and stress-fractures. We aimed to revascularize allografts in porcine and rat models using vascular endothelial growth factor (VEGF), combined with platelet derived growth factor (PDGF) administered through an adeno-associated viral vector. We report the development of vascular tumors resulting from this treatment. Methods: In two separate studies, an identical AAV.VEGF.PDGF vector was used to promote angiogenesis in cryopreserved bone allografts. In 8 Yucatan minipigs, a 3.5 cm segmental tibial defect was reconstructed with a matched allograft, revascularized by placement of a transfected arteriovenous (AV) bundle within the medullary canal. In another experiment, cryopreserved femoral bone allografts coated with AAV.VEGF.PDGF were placed across a 10 mm segmental femoral gap in 10 Lewis rats. Results: Vascular tumors developed in skin and subcutaneous tissues in 5 out of 8 pigs and all of the rats. Histology revealed changes essentially identical to those seen in pyogenic granuloma (lobular capillary hemangioma) in humans. Polymerase chain reaction (PCR) identified the sequence of human VEGF-DNA in all of the sampled tumor tissues. Conclusion: Recombinant AAV gene therapy used to promote angiogenesis in avascular bone risks the development of vascular cutaneous lesions. Gene therapy using an identical AAV.VEGF.PDGF vector should not be considered clinically until safe use can be demonstrated and.concerns regarding chromosomal integration, dose effect and species differences are addressed.
{"title":"Vascular Tumors Result from Adeno-Associated Virus-9 Angiogenic Gene Therapy of Bone Allografts","authors":"E. Rezaie, N. Visser, R. Thaler, F. Khani, P. Friedrich, A. Folpe, D. Deyle, A. Shin, A. J. Wijnen, A. Bishop","doi":"10.24238/13221-12-1-192","DOIUrl":"https://doi.org/10.24238/13221-12-1-192","url":null,"abstract":"Background: Cryopreserved bone allografts are often used to reconstruct segmental bone defects. They are non-viable, which can result in infection, non-union and stress-fractures. We aimed to revascularize allografts in porcine and rat models using vascular endothelial growth factor (VEGF), combined with platelet derived growth factor (PDGF) administered through an adeno-associated viral vector. We report the development of vascular tumors resulting from this treatment. \u0000Methods: In two separate studies, an identical AAV.VEGF.PDGF vector was used to promote angiogenesis in cryopreserved bone allografts. In 8 Yucatan minipigs, a 3.5 cm segmental tibial defect was reconstructed with a matched allograft, revascularized by placement of a transfected arteriovenous (AV) bundle within the medullary canal. In another experiment, cryopreserved femoral bone allografts coated with AAV.VEGF.PDGF were placed across a 10 mm segmental femoral gap in 10 Lewis rats. \u0000Results: Vascular tumors developed in skin and subcutaneous tissues in 5 out of 8 pigs and all of the rats. Histology revealed changes essentially identical to those seen in pyogenic granuloma (lobular capillary hemangioma) in humans. Polymerase chain reaction (PCR) identified the sequence of human VEGF-DNA in all of the sampled tumor tissues. \u0000Conclusion: Recombinant AAV gene therapy used to promote angiogenesis in avascular bone risks the development of vascular cutaneous lesions. Gene therapy using an identical AAV.VEGF.PDGF vector should not be considered clinically until safe use can be demonstrated and.concerns regarding chromosomal integration, dose effect and species differences are addressed.","PeriodicalId":23948,"journal":{"name":"Vascular Cell","volume":"12 1","pages":"3"},"PeriodicalIF":0.0,"publicationDate":"2020-11-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"43324821","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
A. Popa-Wagner, M. Popescu-Drigă, Leonard-Radu Pinosanu, Monica Grigore, Flavia Semida Ghinea, B. Căpitănescu, D. Hermann
Comorbidities like diabetes, arterial hypertension, or comorbidity factors such as hypercholesterolemia is common in elderly persons and are associated with higher risk of stroke. Since stroke afflicts mostly the elderly comorbid patients, it is highly desirable to test the efficacy of cell therapies in an appropriate animal stroke model. Animal models of stroke often ignore age and comorbidities frequently associated with aging, and this could be one of the explanations for unsuccessful bench-to-bedside translation of neuroprotective strategies. In order to mimic more closely the clinical condition, we have established a model of ischemic stroke in aged rats. Using this model, we showed that post-stroke angiogenesis is not impaired in the lesioned, aged brain and conclude that stroke in aged rodent models in reliable and more closely related to the human condition.
{"title":"A clinically relevant model of stroke using aged rats","authors":"A. Popa-Wagner, M. Popescu-Drigă, Leonard-Radu Pinosanu, Monica Grigore, Flavia Semida Ghinea, B. Căpitănescu, D. Hermann","doi":"10.24238/13221-12-1-198","DOIUrl":"https://doi.org/10.24238/13221-12-1-198","url":null,"abstract":"Comorbidities like diabetes, arterial hypertension, or comorbidity factors such as \u0000hypercholesterolemia is common in elderly persons and are associated with higher \u0000risk of stroke. Since stroke afflicts mostly the elderly comorbid patients, it is highly desirable to test the efficacy of cell therapies in an appropriate animal stroke model. Animal models of stroke often ignore age and comorbidities frequently associated with aging, and this could be one of the explanations for unsuccessful bench-to-bedside translation of neuroprotective strategies. In order to mimic more closely the clinical condition, we have established a model of ischemic stroke in aged rats. Using this model, we showed that post-stroke angiogenesis is not impaired in the lesioned, aged brain and conclude that stroke in aged rodent models in reliable and more closely related to the human condition.","PeriodicalId":23948,"journal":{"name":"Vascular Cell","volume":"12 1","pages":"6"},"PeriodicalIF":0.0,"publicationDate":"2020-11-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"48483184","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Nordic Immunohistochemical Quality Control (NordiQC) performs proficiency testing for about 600 pathology laboratories in more than 50 countries. All general results are published on www.nordiqc.org. Over-all, about 30% of the staining results on circulated slides from tissue micro arrays have by an expert group been assessed as insufficient for diagnostic use. This paper describes the results from the two latest NordiQC runs for CD31. Out of 476 stains submitted, 30.5% were considered insufficient, mostly due to too weak or false negative staining reactions. The best results were obtained by use of mouse monoclonal antibody JC70A with an optimized protocol based on efficient heat induced epitope retrieval and a three-step polymer/multimer conjugate as visualization system. The mouse monoclonal antibody 1A10 gave unsatisfactory results in almost all cases.
{"title":"External Quality Assessments of CD31 Immunoassays – the NordiQC experience","authors":"M. Vyberg, S. Nielsen, M. Bzorek, R. Røge","doi":"10.24238/13221-12-1-193","DOIUrl":"https://doi.org/10.24238/13221-12-1-193","url":null,"abstract":"Nordic Immunohistochemical Quality Control (NordiQC) performs proficiency testing for about 600 pathology laboratories in more than 50 countries. All general results are published on www.nordiqc.org. Over-all, about 30% of the staining results on circulated slides from tissue micro arrays have by an expert group been assessed as insufficient for diagnostic use. This paper describes the results from the two latest NordiQC runs for CD31. Out of 476 stains submitted, 30.5% were considered insufficient, mostly due to too weak or false negative staining reactions. The best results were obtained by use of mouse monoclonal antibody JC70A with an optimized protocol based on efficient heat induced epitope retrieval and a three-step polymer/multimer conjugate as visualization system. The mouse monoclonal antibody 1A10 gave unsatisfactory results in almost all cases.","PeriodicalId":23948,"journal":{"name":"Vascular Cell","volume":"12 1","pages":"4"},"PeriodicalIF":0.0,"publicationDate":"2020-07-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"49621623","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
N. Doan, Thang-Quyet Huynh, Sang Tran, Gui Wang, S. Hamlet, V. Dau, D. Dao, N. Nguyen, H. Nguyen, J. Doan, T. Thai, N. Doan, K. N. Truong
Background: The application of Photobiomodulation (PBM), Piezoelectric Surgery (PES) and Concentrated Growth Factors (CGF) in dental implant sinus lift procedure has gained popularity. Aim: To detail a two cases report on the use of PMB, PES, and CGF as a means of enhanced angiogenesis in tissue regeneration in dental implant lateral wall sinus lift procedure. Materials and Methods: This paper presents two cases report on the multi-disciplined approach using PBM, PES, and CGF as a method of enriched angiogenesis in tissue regeneration in dental implant sinus lift technique. In both patients, the sinus lateral windows were created using PES and the sinus membrane was raised to make a new partition. Surface modified dental implants (average 8 mm long) were inserted concurrently, packed with autologous fibrin-rich CGF, and then lastly induced PBM using Multiwave Locked System (MLS) laser. Radiographic and clinical evaluation was implemented to validate the efficacy of this multi-disciplined approach. Results and discussion: Postoperative revival was ordinary with no noteworthy postoperative complications. Wound closure/angiogenesis occurred shortly after day one. New bone formation in all augmented maxillary sinuses was detected alongside the implants on plain radiographs and on cone-beam computed tomograms. The patients were very happy with the overall treatment (>80%) and the success rate of implant was 100% after a usual 10 months loading period. PBM, PES, and CGF enhance angiogenesis/wound healing by speeding up wound approximation/healing, lessening the followings: postoperative pain, swelling, bleeding, speech impairment, analgesic use, and trismus. Conclusion: Using PBM, PES, and CGF as a method to enrich angiogenesis/wound healing in sinus lift rendered initial phase of satisfaction, simplicity, effectiveness, minimal complication, enhanced angiogenesis/wound healing with no cross infection and allergic reaction. Keywords photobiomodulation - piezoelectric surgery - concentrated growth factors - sinus augmentation - angiogenesis/wound healing
{"title":"Multidisciplinary approach to maximize angiogenesis and wound healing using piezoelectric surgery, concentrated growth factors and photobiomodulation for dental implant placement surgery involving lateral wall sinus lift: two case reports.","authors":"N. Doan, Thang-Quyet Huynh, Sang Tran, Gui Wang, S. Hamlet, V. Dau, D. Dao, N. Nguyen, H. Nguyen, J. Doan, T. Thai, N. Doan, K. N. Truong","doi":"10.24238/13221-12-1-186","DOIUrl":"https://doi.org/10.24238/13221-12-1-186","url":null,"abstract":"Background: The application of Photobiomodulation (PBM), Piezoelectric Surgery (PES) and Concentrated Growth Factors (CGF) in dental implant sinus lift procedure has gained popularity. Aim: To detail a two cases report on the use of PMB, PES, and CGF as a means of enhanced angiogenesis in tissue regeneration in dental implant lateral wall sinus lift procedure. Materials and Methods: This paper presents two cases report on the multi-disciplined approach using PBM, PES, and CGF as a method of enriched angiogenesis in tissue regeneration in dental implant sinus lift technique. In both patients, the sinus lateral windows were created using PES and the sinus membrane was raised to make a new partition. Surface modified dental implants (average 8 mm long) were inserted concurrently, packed with autologous fibrin-rich CGF, and then lastly induced PBM using Multiwave Locked System (MLS) laser. Radiographic and clinical evaluation was implemented to validate the efficacy of this multi-disciplined approach. Results and discussion: Postoperative revival was ordinary with no noteworthy postoperative complications. Wound closure/angiogenesis occurred shortly after day one. New bone formation in all augmented maxillary sinuses was detected alongside the implants on plain radiographs and on cone-beam computed tomograms. The patients were very happy with the overall treatment (>80%) and the success rate of implant was 100% after a usual 10 months loading period. PBM, PES, and CGF enhance angiogenesis/wound healing by speeding up wound approximation/healing, lessening the followings: postoperative pain, swelling, bleeding, speech impairment, analgesic use, and trismus. Conclusion: Using PBM, PES, and CGF as a method to enrich angiogenesis/wound healing in sinus lift rendered initial phase of satisfaction, simplicity, effectiveness, minimal complication, enhanced angiogenesis/wound healing with no cross infection and allergic reaction. \u0000 \u0000Keywords \u0000photobiomodulation - piezoelectric surgery - concentrated growth factors - sinus augmentation - angiogenesis/wound healing","PeriodicalId":23948,"journal":{"name":"Vascular Cell","volume":"12 1","pages":"2"},"PeriodicalIF":0.0,"publicationDate":"2020-04-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"45247808","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Non-union of scaphoid bone fractures, though an uncommon occurance, are a signficant cause of morbidity in young patients. This review outlines the current understanding of vascularised bone grafts and non-union, and examines the most current clinical literature regarding the role of these procedures in modern orthopaedic practice. Composite evidence from level III studies would support using osseous grafts on a vascular pedicle for patients with non-union of the proximal end of the scaphoid with associated avascular necrosis and in cases of revision surgery where a previous non-vascularised graft has failed to achieve bony union.
{"title":"Surgical angiogenesis for scaphoid non-union: a literature review","authors":"J. Corcoran, I. Nusem, Usama Zafar","doi":"10.24238/13221-12-1-187","DOIUrl":"https://doi.org/10.24238/13221-12-1-187","url":null,"abstract":"Non-union of scaphoid bone fractures, though an uncommon occurance, are a signficant cause of morbidity in young patients. This review outlines the current understanding of vascularised bone grafts and non-union, and examines the most current clinical literature regarding the role of these procedures in modern orthopaedic practice. Composite evidence from level III studies would support using osseous grafts on a vascular pedicle for patients with non-union of the proximal end of the scaphoid with associated avascular necrosis and in cases of revision surgery where a previous non-vascularised graft has failed to achieve bony union.","PeriodicalId":23948,"journal":{"name":"Vascular Cell","volume":"12 1","pages":"1"},"PeriodicalIF":0.0,"publicationDate":"2020-01-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"42190226","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Xiao-Ju Wan, Zifu Zhang, Lei Rui, R. Wilson, Xiaoning Wu, Xin Liu
Chicken chorioallantoic membrane (CAM) models have been applied as an affordable and efficient angiogenesis model for many years in relevant areas such as cancer angiogenesis and cardiovascular sciences. However, this model has intrinsic weaknesses such as the difficulty of operation and the limited size of the viewing windows. Efforts of trying to improve this model, such as transferring the embryos into petri dishes, has led to compromised survival rate of the embryos. In this study we improve the workflow by using surrogate egg shells. The images obtained from the viewing windows of the surrogate shells allow us to apply automated image analysis. This CAM model in surrogate shells combined with automated image analysis significantly decreases the labour whilst also increasing the data quality, when compared to traditional CAM models. Furthermore, to demonstrate the potential of our model, we have investigated the effects of a range of chylomicrons, extracted from murine and human samples, using the improved CAM model, to seek clues to elucidate the controversial roles of high level chylomicrons (CMs) in hypertriglyceridaemia (HTG) on atherosclerosis. We show that both native and modified chylomicrons (CMs) promote in vitro and in vivo angiogenesis. As angiogenesis is a risk factor in atherosclerosis our results provide a new mechanism for the effect of hypertriglyceridaemia (HTG) on atherosclerosis development. In summary, we demonstrate an improved CAM model aided by automated image analysis, we demonstrate the potential of this model by demonstrating interfered angiogenesis caused by HTG and discuss the impact this could potentially cause other pathological processes, such as atherosclerosis or carcinogenesis. Furthermore, the significantly low cost of CAM models compared with traditional murine models for cardiovascular research will have potential 3Rs (replacement, reduction and refinement) significance for the research communities, especially for laboratories with limited budgets or regulatory restrictions.
{"title":"An Improved In Vivo Angiogenesis Model of Chicken Chorioallantoic Membranes in Surrogate Shells Revealed the Pro-angiogenesis Effects of Chylomicrons","authors":"Xiao-Ju Wan, Zifu Zhang, Lei Rui, R. Wilson, Xiaoning Wu, Xin Liu","doi":"10.24238/13221-11-1-178","DOIUrl":"https://doi.org/10.24238/13221-11-1-178","url":null,"abstract":"Chicken chorioallantoic membrane (CAM) models have been applied as an affordable and efficient angiogenesis model for many years in relevant areas such as cancer angiogenesis and cardiovascular sciences. However, this model has intrinsic weaknesses such as the difficulty of operation and the limited size of the viewing windows. Efforts of trying to improve this model, such as transferring the embryos into petri dishes, has led to compromised survival rate of the embryos. In this study we improve the workflow by using surrogate egg shells. The images obtained from the viewing windows of the surrogate shells allow us to apply automated image analysis. This CAM model in surrogate shells combined with automated image analysis significantly decreases the labour whilst also increasing the data quality, when compared to traditional CAM models. Furthermore, to demonstrate the potential of our model, we have investigated the effects of a range of chylomicrons, extracted from murine and human samples, using the improved CAM model, to seek clues to elucidate the controversial roles of high level chylomicrons (CMs) in hypertriglyceridaemia (HTG) on atherosclerosis. We show that both native and modified chylomicrons (CMs) promote in vitro and in vivo angiogenesis. As angiogenesis is a risk factor in atherosclerosis our results provide a new mechanism for the effect of hypertriglyceridaemia (HTG) on atherosclerosis development. In summary, we demonstrate an improved CAM model aided by automated image analysis, we demonstrate the potential of this model by demonstrating interfered angiogenesis caused by HTG and discuss the impact this could potentially cause other pathological processes, such as atherosclerosis or carcinogenesis. Furthermore, the significantly low cost of CAM models compared with traditional murine models for cardiovascular research will have potential 3Rs (replacement, reduction and refinement) significance for the research communities, especially for laboratories with limited budgets or regulatory restrictions.","PeriodicalId":23948,"journal":{"name":"Vascular Cell","volume":"1 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2019-02-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"43575901","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
J. Pagliuso, S. Parry, Z. Haffajee, T. Badrick, Keith W. Miller
Julia Pagliuso, Suzanne Parry, Zenobia Haffajee, Tony Badrick, Keith Miller Background . One important initiative that commenced at the Royal College of Pathologists of Australasia Quality Assurance Program (RCPAQAP) in 2017 was the collaboration with United Kingdom National External Quality Assessment Scheme (UK NEQAS) Immunocytochemistry (ICC) and In-Situ Hybridization (ISH) for the challenging implementation of a PD-L1 immunohistochemistry (IHC) proficiency testing program for non-small cell lung carcinoma (NSCLC). A RCPAQAP participant survey in 2016 showed that only eight laboratories were performing PD-L1 testing. The aim of the collaboration was to increase the sample size of the pilot program to provide meaningful results that could be reported back to RCPAQAP participants with appropriate recommendations. Other challenges of assessment included standardising the clinical cut-offs for positivity for each commercial assay, interpretation of laboratory developed tests (LDTs), using appropriate tissue to cover the critical interpretation points for each assay, interchangeability of clones and interpretation proficiency testing. Methods . The use of a ‘Gold Standard’ for each commercial assay was used as a baseline to compare participant results and tumour proportion score bin categories were implemented to harmonise interpretation across clones. Conclusions . The findings of the pre-pilot test suggest that the use of a clinically validated PD-L1 IHC assay performs better during assessment than adopting a laboratory developed test (LDT). The assessment committee also concluded that tonsil showed a better dynamic range of positivity than placenta. It was acknowledged that participants are limited by the platforms they have available and so it was suggested that validating an optimal method against the clinical assay and continual verification of the test may produce the expected result. The next big challenge is to extend proficiency testing from technical to interpretation. This is being implemented globally via the International Quality Network for Pathology (IQNPath) with participation through local External Quality Assurance programs, including RCPAQAP.
Julia Pagliuso, Suzanne Parry, Zenobia Haffajee, Tony Badrick, Keith Miller2017年，澳大利亚皇家病理学家学院质量保证计划(RCPAQAP)启动了一项重要举措，即与英国国家外部质量评估计划(UK NEQAS)免疫细胞化学(ICC)和原位杂交(ISH)合作，以挑战性地实施非小细胞肺癌(NSCLC)的PD-L1免疫组织化学(IHC)能力测试计划。2016年RCPAQAP参与者调查显示，只有8家实验室进行PD-L1检测。合作的目的是增加试点项目的样本量，以提供有意义的结果，并向RCPAQAP参与者报告并提供适当的建议。评估的其他挑战包括使每种商业化验的阳性临床截止标准标准化、实验室开发的化验(LDTs)的解释、使用适当的组织覆盖每种化验的关键解释点、克隆的互换性和解释能力测试。方法。使用每个商业测定的“金标准”作为基线来比较参与者的结果，并实施肿瘤比例评分bin类别以协调跨克隆的解释。结论。预先导试验的结果表明，在评估过程中，使用临床验证的PD-L1免疫组化检测比采用实验室开发的检测(LDT)效果更好。评估委员会还得出结论，扁桃体比胎盘表现出更好的动态阳性范围。与会者承认，参与者受到现有平台的限制，因此建议针对临床分析验证最佳方法并不断验证测试可能产生预期结果。下一个重大挑战是将熟练程度测试从技术测试扩展到口译测试。这是通过国际病理质量网络(IQNPath)在全球范围内实施的，并通过当地的外部质量保证计划(包括RCPAQAP)参与。
{"title":"The Challenges of Implementing a PD-L1 Proficiency Testing Program in Australia","authors":"J. Pagliuso, S. Parry, Z. Haffajee, T. Badrick, Keith W. Miller","doi":"10.24238/13221-10-1-180","DOIUrl":"https://doi.org/10.24238/13221-10-1-180","url":null,"abstract":"Julia Pagliuso, Suzanne Parry, Zenobia Haffajee, Tony Badrick, Keith Miller Background . One important initiative that commenced at the Royal College of Pathologists of Australasia Quality Assurance Program (RCPAQAP) in 2017 was the collaboration with United Kingdom National External Quality Assessment Scheme (UK NEQAS) Immunocytochemistry (ICC) and In-Situ Hybridization (ISH) for the challenging implementation of a PD-L1 immunohistochemistry (IHC) proficiency testing program for non-small cell lung carcinoma (NSCLC). A RCPAQAP participant survey in 2016 showed that only eight laboratories were performing PD-L1 testing. The aim of the collaboration was to increase the sample size of the pilot program to provide meaningful results that could be reported back to RCPAQAP participants with appropriate recommendations. Other challenges of assessment included standardising the clinical cut-offs for positivity for each commercial assay, interpretation of laboratory developed tests (LDTs), using appropriate tissue to cover the critical interpretation points for each assay, interchangeability of clones and interpretation proficiency testing. Methods . The use of a ‘Gold Standard’ for each commercial assay was used as a baseline to compare participant results and tumour proportion score bin categories were implemented to harmonise interpretation across clones. Conclusions . The findings of the pre-pilot test suggest that the use of a clinically validated PD-L1 IHC assay performs better during assessment than adopting a laboratory developed test (LDT). The assessment committee also concluded that tonsil showed a better dynamic range of positivity than placenta. It was acknowledged that participants are limited by the platforms they have available and so it was suggested that validating an optimal method against the clinical assay and continual verification of the test may produce the expected result. The next big challenge is to extend proficiency testing from technical to interpretation. This is being implemented globally via the International Quality Network for Pathology (IQNPath) with participation through local External Quality Assurance programs, including RCPAQAP.","PeriodicalId":23948,"journal":{"name":"Vascular Cell","volume":"1 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2018-12-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"45220139","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
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