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1. On the Value of PHH3 for Mitotic Figure Detection on H&E-stained Images

Author

Ganz, Jonathan, Marzahl, Christian, Ammeling, Jonas, Richter, Barbara, Puget, Chloé, Denk, Daniela, Demeter, Elena A., Tabaran, Flaviu A., Wasinger, Gabriel, Lipnik, Karoline, Tecilla, Marco, Valentine, Matthew J., Dark, Michael J., Abele, Niklas, Bolfa, Pompei, Erber, Ramona, Klopfleisch, Robert, Merz, Sophie, Donovan, Taryn A., Jabari, Samir, Bertram, Christof A., Breininger, Katharina, and Aubreville, Marc

Subjects
Computer Science - Computer Vision and Pattern Recognition, Quantitative Biology - Quantitative Methods
Abstract

The count of mitotic figures (MFs) observed in hematoxylin and eosin (H&E)-stained slides is an important prognostic marker as it is a measure for tumor cell proliferation. However, the identification of MFs has a known low inter-rater agreement. Deep learning algorithms can standardize this task, but they require large amounts of annotated data for training and validation. Furthermore, label noise introduced during the annotation process may impede the algorithm's performance. Unlike H&E, the mitosis-specific antibody phospho-histone H3 (PHH3) specifically highlights MFs. Counting MFs on slides stained against PHH3 leads to higher agreement among raters and has therefore recently been used as a ground truth for the annotation of MFs in H&E. However, as PHH3 facilitates the recognition of cells indistinguishable from H&E stain alone, the use of this ground truth could potentially introduce noise into the H&E-related dataset, impacting model performance. This study analyzes the impact of PHH3-assisted MF annotation on inter-rater reliability and object level agreement through an extensive multi-rater experiment. We found that the annotators' object-level agreement increased when using PHH3-assisted labeling. Subsequently, MF detectors were evaluated on the resulting datasets to investigate the influence of PHH3-assisted labeling on the models' performance. Additionally, a novel dual-stain MF detector was developed to investigate the interpretation-shift of PHH3-assisted labels used in H&E, which clearly outperformed single-stain detectors. However, the PHH3-assisted labels did not have a positive effect on solely H&E-based models. The high performance of our dual-input detector reveals an information mismatch between the H&E and PHH3-stained images as the cause of this effect., Comment: 10 pages, 5 figures, 1 Table

Published
2024
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2. Nuclear Pleomorphism in Canine Cutaneous Mast Cell Tumors: Comparison of Reproducibility and Prognostic Relevance between Estimates, Manual Morphometry and Algorithmic Morphometry

Author

Haghofer, Andreas, Parlak, Eda, Bartel, Alexander, Donovan, Taryn A., Assenmacher, Charles-Antoine, Bolfa, Pompei, Dark, Michael J., Fuchs-Baumgartinger, Andrea, Klang, Andrea, Jäger, Kathrin, Klopfleisch, Robert, Merz, Sophie, Richter, Barbara, Schulman, F. Yvonne, Janout, Hannah, Ganz, Jonathan, Scharinger, Josef, Aubreville, Marc, Winkler, Stephan M., Kiupel, Matti, and Bertram, Christof A.

Subjects
Computer Science - Computer Vision and Pattern Recognition
Abstract

Variation in nuclear size and shape is an important criterion of malignancy for many tumor types; however, categorical estimates by pathologists have poor reproducibility. Measurements of nuclear characteristics (morphometry) can improve reproducibility, but manual methods are time consuming. The aim of this study was to explore the limitations of estimates and develop alternative morphometric solutions for canine cutaneous mast cell tumors (ccMCT). We assessed the following nuclear evaluation methods for measurement accuracy, reproducibility, and prognostic utility: 1) anisokaryosis (karyomegaly) estimates by 11 pathologists; 2) gold standard manual morphometry of at least 100 nuclei; 3) practicable manual morphometry with stratified sampling of 12 nuclei by 9 pathologists; and 4) automated morphometry using a deep learning-based segmentation algorithm. The study dataset comprised 96 ccMCT with available outcome information. The study dataset comprised 96 ccMCT with available outcome information. Inter-rater reproducibility of karyomegaly estimates was low ($\kappa$ = 0.226), while it was good (ICC = 0.654) for practicable morphometry of the standard deviation (SD) of nuclear size. As compared to gold standard manual morphometry (AUC = 0.839, 95% CI: 0.701 - 0.977), the prognostic value (tumor-specific survival) of SDs of nuclear area for practicable manual morphometry (12 nuclei) and automated morphometry were high with an area under the ROC curve (AUC) of 0.868 (95% CI: 0.737 - 0.991) and 0.943 (95% CI: 0.889 - 0.996), respectively. This study supports the use of manual morphometry with stratified sampling of 12 nuclei and algorithmic morphometry to overcome the poor reproducibility of estimates.

Published
2023

3. Information mismatch in PHH3-assisted mitosis annotation leads to interpretation shifts in H&E slide analysis

Author

Ganz, Jonathan, Marzahl, Christian, Ammeling, Jonas, Rosbach, Emely, Richter, Barbara, Puget, Chloé, Denk, Daniela, Demeter, Elena A., Tăbăran, Flaviu A., Wasinger, Gabriel, Lipnik, Karoline, Tecilla, Marco, Valentine, Matthew J., Dark, Michael J., Abele, Niklas, Bolfa, Pompei, Erber, Ramona, Klopfleisch, Robert, Merz, Sophie, Donovan, Taryn A., Jabari, Samir, Bertram, Christof A., Breininger, Katharina, and Aubreville, Marc

Published
2024
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4. RNA in situ hybridisation as a molecular diagnostic technique targeting IBA‐1 and CD204 in canine histiocytic sarcoma

Author

Engelien, Julia L, Lejeune, Amandine T, Dark, Michael J, Milner, Rowan J, and Shiomitsu, Keijiro

Subjects
Veterinary Sciences, Agricultural, Veterinary and Food Sciences, Biotechnology, Genetics, Cancer, Aetiology, 2.1 Biological and endogenous factors, Animals, Biomarkers, Dog Diseases, Dogs, Histiocytic Sarcoma, Immunohistochemistry, Molecular Diagnostic Techniques, Neoplasms, RNA, diagnosis, dog, histiocytic disorder, ionised calcium-binding adapter molecule 1, macrophage scavenger receptor, RNAscope, Veterinary sciences
Abstract

BackgroundCanine histiocytic sarcoma (HS) is an aggressive cancer with morphologically variable features; therefore, obtaining a definitive diagnosis can be challenging. Two proteins, IBA-1, ionised calcium-binding adapter molecule 1, and CD204, a macrophage scavenger receptor, have been shown to be specific immunohistochemical markers helpful in distinguishing HS from other tumour types with similar morphological features.ObjectivesThis study was performed to demonstrate the use of RNA in situ hybridisation (ISH) technology allowing single-molecule RNA visualisation in formalin-fixed paraffin-embedded (FFPE) tissues as a molecular tool for the diagnosis of canine HS.MethodsReverse transcription polymerase chain reaction (RT-PCR) and western blot analysis for IBA-1 and CD204 were performed to correlate gene expression and protein expression of these two markers in the histiocytic sarcoma DH82 cell line. RNA-ISH for IBA-1 and CD204 was performed on the DH82 cell line to validate the RNA-ISH probes. RNA-ISH and immunohistochemistry (IHC) were performed in clinical HS FFPE samples to demonstrate mRNA and protein expression of IBA-1 and CD204. FFPE archived samples of canine round cell tumours, melanoma and anaplastic sarcoma were used as negative controls.ResultsRNA-ISH and IHC showed moderate to strong expression for IBA-1 and CD204 in the neoplastic cells in both the canine DH82 cell line and the archived canine HS samples. RNA-ISH and IHC showed scattered positive staining in the control tumours samples, consistent with macrophagic infiltration.ConclusionRNA-ISH for CD204 and IBA-1 appeared to have a high specificity and sensitivity in our samples and may be an additional valuable diagnostic technique in identifying HS.

Published
2022

5. Mitosis domain generalization in histopathology images — The MIDOG challenge

Author

Aubreville, Marc, Stathonikos, Nikolas, Bertram, Christof A., Klopfleisch, Robert, ter Hoeve, Natalie, Ciompi, Francesco, Wilm, Frauke, Marzahl, Christian, Donovan, Taryn A., Maier, Andreas, Breen, Jack, Ravikumar, Nishant, Chung, Youjin, Park, Jinah, Nateghi, Ramin, Pourakpour, Fattaneh, Fick, Rutger H.J., Ben Hadj, Saima, Jahanifar, Mostafa, Shephard, Adam, Dexl, Jakob, Wittenberg, Thomas, Kondo, Satoshi, Lafarge, Maxime W., Koelzer, Viktor H., Liang, Jingtang, Wang, Yubo, Long, Xi, Liu, Jingxin, Razavi, Salar, Khademi, April, Yang, Sen, Wang, Xiyue, Erber, Ramona, Klang, Andrea, Lipnik, Karoline, Bolfa, Pompei, Dark, Michael J., Wasinger, Gabriel, Veta, Mitko, and Breininger, Katharina

Published
2023
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7. Automated Nuclear Morphometry: A Deep Learning Approach for Prognostication in Canine Pulmonary Carcinoma to Enhance Reproducibility.

Author

Glahn, Imaine, Haghofer, Andreas, Donovan, Taryn A., Degasperi, Brigitte, Bartel, Alexander, Kreilmeier-Berger, Theresa, Hyndman, Philip S., Janout, Hannah, Assenmacher, Charles-Antoine, Bartenschlager, Florian, Bolfa, Pompei, Dark, Michael J., Klang, Andrea, Klopfleisch, Robert, Merz, Sophie, Richter, Barbara, Schulman, F. Yvonne, Ganz, Jonathan, Scharinger, Josef, and Aubreville, Marc

Subjects
DEEP learning, MORPHOMETRICS, NUCLEAR shapes, CARCINOMA, PROGNOSIS, PROGNOSTIC tests
Abstract

Simple Summary: We investigated a new method for diagnosing and predicting outcomes in canine pulmonary carcinoma. We developed a deep learning-based algorithm that accurately detects tumor nuclei and subsequently measures size and shape parameters. The variation in nuclear size and shape (nuclear pleomorphism) is a crucial malignancy criterion used in the current grading system for canine pulmonary carcinoma. Pathologists currently evaluate it and classify it according to a three-tier system. Manual morphometry is a more objective approach where tumor nuclei are individually encircled and analyzed. This task can be easily performed by an algorithm. Our algorithm's accuracy in correctly detecting and segmenting tumor nuclei was considered good when compared to manual morphometry. By comparing automated morphometry with conventional prognostic tests, such as pathologists' estimates, mitotic count, histological grading, and clinical staging, we found that our approach was equally accurate in terms of prognostic value. The algorithm's advantage lies in its high reproducibility and efficiency. Automated evaluation of nuclear pleomorphism can enhance the efficiency and reliability of canine pulmonary carcinoma diagnosis and grading, effectively addressing issues of inter-observer reproducibility. However, further optimization of the algorithm and validation with a larger study group is necessary to confirm our findings. The integration of deep learning-based tools into diagnostic workflows is increasingly prevalent due to their efficiency and reproducibility in various settings. We investigated the utility of automated nuclear morphometry for assessing nuclear pleomorphism (NP), a criterion of malignancy in the current grading system in canine pulmonary carcinoma (cPC), and its prognostic implications. We developed a deep learning-based algorithm for evaluating NP (variation in size, i.e., anisokaryosis and/or shape) using a segmentation model. Its performance was evaluated on 46 cPC cases with comprehensive follow-up data regarding its accuracy in nuclear segmentation and its prognostic ability. Its assessment of NP was compared to manual morphometry and established prognostic tests (pathologists' NP estimates (n = 11), mitotic count, histological grading, and TNM-stage). The standard deviation (SD) of the nuclear area, indicative of anisokaryosis, exhibited good discriminatory ability for tumor-specific survival, with an area under the curve (AUC) of 0.80 and a hazard ratio (HR) of 3.38. The algorithm achieved values comparable to manual morphometry. In contrast, the pathologists' estimates of anisokaryosis resulted in HR values ranging from 0.86 to 34.8, with slight inter-observer reproducibility (k = 0.204). Other conventional tests had no significant prognostic value in our study cohort. Fully automated morphometry promises a time-efficient and reproducible assessment of NP with a high prognostic value. Further refinement of the algorithm, particularly to address undersegmentation, and application to a larger study population are required. [ABSTRACT FROM AUTHOR]

Published
2024
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9. Telangiectatic osteosarcoma in four dogs: Cytologic, histopathologic, cytochemical, and immunohistochemical findings.

Author

Cagle, Laura A., Maisel, Morgan, Conrado, Francisco O., Wait, Courtney, Peper, Katherine, Lochhead, Tannis, Vo, Thao, Dolan, Jacqueline K., de Oliveira, Helena Hauck, Bosch, Sarah, Walker, Randall, Fox‐Alvarez, Stacey A., Porter, Erin, Carrera‐Justiz, Sheila, Lanier, Christopher J., Hoffmann, Aline Rodrigues, Dark, Michael J., and Sharkey, Leslie C.

Subjects
OSTEOSARCOMA, BLOOD coagulation factor VIII, CYTODIAGNOSIS, ALKALINE phosphatase, ANGIOSARCOMA, DOGS
Abstract

Telangiectatic osteosarcoma is a rare variant of osteosarcoma histologically and clinically similar to hemangiosarcoma (HSA). This case series describes the imaging and cytologic features of four histologically confirmed telangiectatic osteosarcomas, including the use of cytochemical stains. Alkaline phosphatase (ALP) was applied to Wright–Giemsa‐stained cytology slides, and Factor VIII immunohistochemistry was evaluated. Cytologic characteristics included atypical mesenchymal cells with evidence of acute and chronic hemorrhage. Telangiectatic osteosarcoma cases had positive ALP cytochemical staining, while control HSA cases were negative. Factor VIII immunohistochemistry was negative in telangiectatic osteosarcoma and positive in HSA. Cytologic diagnosis of telangiectatic osteosarcoma with positive ALP cytochemical staining can help differentiate this neoplasm from HSA. [ABSTRACT FROM AUTHOR]

Published
2024
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12. Mitosis domain generalization in histopathology images - The MIDOG challenge

Author

Pathologie Support, Pathologie Groep Van Diest, Aubreville, Marc, Stathonikos, Nikolas, Bertram, Christof A, Klopfleisch, Robert, Ter Hoeve, Natalie, Ciompi, Francesco, Wilm, Frauke, Marzahl, Christian, Donovan, Taryn A, Maier, Andreas, Breen, Jack, Ravikumar, Nishant, Chung, Youjin, Park, Jinah, Nateghi, Ramin, Pourakpour, Fattaneh, Fick, Rutger H J, Ben Hadj, Saima, Jahanifar, Mostafa, Shephard, Adam, Dexl, Jakob, Wittenberg, Thomas, Kondo, Satoshi, Lafarge, Maxime W, Koelzer, Viktor H, Liang, Jingtang, Wang, Yubo, Long, Xi, Liu, Jingxin, Razavi, Salar, Khademi, April, Yang, Sen, Wang, Xiyue, Erber, Ramona, Klang, Andrea, Lipnik, Karoline, Bolfa, Pompei, Dark, Michael J, Wasinger, Gabriel, Veta, Mitko, Breininger, Katharina, Pathologie Support, Pathologie Groep Van Diest, Aubreville, Marc, Stathonikos, Nikolas, Bertram, Christof A, Klopfleisch, Robert, Ter Hoeve, Natalie, Ciompi, Francesco, Wilm, Frauke, Marzahl, Christian, Donovan, Taryn A, Maier, Andreas, Breen, Jack, Ravikumar, Nishant, Chung, Youjin, Park, Jinah, Nateghi, Ramin, Pourakpour, Fattaneh, Fick, Rutger H J, Ben Hadj, Saima, Jahanifar, Mostafa, Shephard, Adam, Dexl, Jakob, Wittenberg, Thomas, Kondo, Satoshi, Lafarge, Maxime W, Koelzer, Viktor H, Liang, Jingtang, Wang, Yubo, Long, Xi, Liu, Jingxin, Razavi, Salar, Khademi, April, Yang, Sen, Wang, Xiyue, Erber, Ramona, Klang, Andrea, Lipnik, Karoline, Bolfa, Pompei, Dark, Michael J, Wasinger, Gabriel, Veta, Mitko, and Breininger, Katharina

Published
2023

16. Anaplasma

Author

Brayton, Kelly A., Dark, Michael J., Palmer, Guy H., Nene, Vishvanath, editor, and Kole, Chittaranjan, editor

Published
2009
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17. Overview of the Veterinary Cancer Guidelines and Protocols group's "Developing, reporting and validating histologic tumor grading systems".

Author

Schulman, F. Yvonne, Bertram, Christof A., Meuten, Donald J., Moore, Frances M., Avallone, Giancarlo, Bartel, Alexander, Bolfa, Pompei, Camus, Melinda, Chambers, James K., Dark, Michael J., Dervisis, Nick, Dobromylskyj, Melanie J., Donovan, Taryn A., Foster, Robert A., Krimer, Paula M., Miller, Andrew, Milovancev, Milan, Roccabianca, Paola, Selmic, Laura E., and Wood, Geoff A.

Subjects
TUMOR grading
Abstract

The Veterinary Cancer Guidelines and Protocols (VCGP) group has developed guidelines for developing, reporting, and validating histologic tumor grading systems. These guidelines aim to standardize tumor evaluation in order to improve the care of animals with cancer. The grading systems should be reproducible, relevant to prognosis, and realistic in terms of applicability in a routine diagnostic setting. The VCGP group encourages collaboration from various disciplines and emphasizes the importance of standardized clinical outcomes and statistical assessment. The guidelines also suggest comparing histologic grade with other assays and encourage the publication of grading systems in peer-reviewed journals with sufficient details for replication and validation. Validation studies should be conducted before implementing the grading system on clinical cases. [Extracted from the article]

Published
2024
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21. Veterinary Pathology

Author

Meuten, Donald J., Moore, Frances M., Donovan, Taryn A., Bertram, Christof A., Klopfleisch, Robert, Foster, Robert A., Smedley, Rebecca C., Dark, Michael J., Milovancev, Milan, Stromberg, Paul, Williams, Bruce H., Aubreville, Marc, Avallone, Giancarlo, Bolfa, Pompei, Cullen, John, Dennis, Michelle M., Goldschmidt, Michael, Luong, Richard, Miller, Andrew D., Miller, Margaret A., Munday, John S., Roccabianca, Paola, Salas, Elisa N., Schulman, F. Yvonne, Laufer-Amorim, Renee, Asakawa, Midori G., Craig, Linden, Dervisis, Nikolaos G., Esplin, D. Glen, George, Jeanne W., Hauck, Marlene, Kagawa, Yumiko, Kiupel, Matti, Linder, Keith, Meichner, Kristina, Marconato, Laura, Oblak, Michelle L., Santos, Renato L., Simpson, R. Mark, Tvedten, Harold, and Whitley, Derick

Subjects
standardization, validation, MITOTIC FIGURES, protocols, Reproducibility of Results, VASCULAR INVASION, PERIVASCULAR WALL TUMORS, SOFT-TISSUE SARCOMAS, SURGICAL EXCISION, Neoplasms, oncology, PROGNOSTIC-SIGNIFICANCE, NERVE SHEATH TUMORS, BREAST-CANCER, Animals, guidelines, IMMUNOHISTOCHEMICAL MARKERS, Pathology, Veterinary, MAST-CELL TUMORS, Cancer
Abstract

Standardization of tumor assessment lays the foundation for validation of grading systems, permits reproducibility of oncologic studies among investigators, and increases confidence in the significance of study results. Currently, there is minimal methodological standardization for assessing tumors in veterinary medicine, with few attempts to validate published protocols and grading schemes. The current article attempts to address these shortcomings by providing standard guidelines for tumor assessment parameters and protocols for evaluating specific tumor types. More detailed information is available in the Supplemental Files, the intention of which is 2-fold: publication as part of this commentary, but more importantly, these will be available as “living documents” on a website (www.vetcancerprotocols.org), which will be updated as new information is presented in the peer-reviewed literature. Our hope is that veterinary pathologists will agree that this initiative is needed, and will contribute to and utilize this information for routine diagnostic work and oncologic studies. Journal editors and reviewers can utilize checklists to ensure publications include sufficient detail and standardized methods of tumor assessment. To maintain the relevance of the guidelines and protocols, it is critical that the information is periodically updated and revised as new studies are published and validated with the intent of providing a repository of this information. Our hope is that this initiative (a continuation of efforts published in this journal in 2011) will facilitate collaboration and reproducibility between pathologists and institutions, increase case numbers, and strengthen clinical research findings, thus ensuring continued progress in veterinary oncologic pathology and improving patient care. Accepted version

Published
2021

22. International Guidelines for Veterinary Tumor Pathology: A Call to Action

Author

Meuten, Donald J., primary, Moore, Frances M., additional, Donovan, Taryn A., additional, Bertram, Christof A., additional, Klopfleisch, Robert, additional, Foster, Robert A., additional, Smedley, Rebecca C., additional, Dark, Michael J., additional, Milovancev, Milan, additional, Stromberg, Paul, additional, Williams, Bruce H., additional, Aubreville, Marc, additional, Avallone, Giancarlo, additional, Bolfa, Pompei, additional, Cullen, John, additional, Dennis, Michelle M., additional, Goldschmidt, Michael, additional, Luong, Richard, additional, Miller, Andrew D., additional, Miller, Margaret A., additional, Munday, John S., additional, Roccabianca, Paola, additional, Salas, Elisa N., additional, Schulman, F. Yvonne, additional, Laufer-Amorim, Renee, additional, Asakawa, Midori G., additional, Craig, Linden, additional, Dervisis, Nick, additional, Esplin, D. Glen, additional, George, Jeanne W., additional, Hauck, Marlene, additional, Kagawa, Yumiko, additional, Kiupel, Matti, additional, Linder, Keith, additional, Meichner, Kristina, additional, Marconato, Laura, additional, Oblak, Michelle L., additional, Santos, Renato L., additional, Simpson, R. Mark, additional, Tvedten, Harold, additional, and Whitley, Derick, additional

Published
2021
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23. Supplemental Material, sj-pdf-9-vet-10.1177_03009858211013712 - International Guidelines for Veterinary Tumor Pathology: A Call to Action

Author

Meuten, Donald J., Moore, Frances M., Donovan, Taryn A., Bertram, Christof A., Klopfleisch, Robert, Foster, Robert A., Smedley, Rebecca C., Dark, Michael J., Milovancev, Milan, Stromberg, Paul, Williams, Bruce H., Aubreville, Marc, Avallone, Giancarlo, Bolfa, Pompei, Cullen, John, Dennis, Michelle M., Goldschmidt, Michael, Luong, Richard, Miller, Andrew D., Miller, Margaret A., Munday, John S., Roccabianca, Paola, Salas, Elisa N., Schulman, F. Yvonne, Laufer-Amorim, Renee, Asakawa, Midori G., Craig, Linden, Dervisis, Nick, Esplin, D. Glen, George, Jeanne W., Hauck, Marlene, Kagawa, Yumiko, Kiupel, Matti, Linder, Keith, Meichner, Kristina, Marconato, Laura, Oblak, Michelle L., Santos, Renato L., Simpson, R. Mark, Tvedten, Harold, and Whitley, Derick

Subjects
70706 Veterinary Medicine, FOS: Clinical medicine, FOS: Veterinary sciences, 111599 Pharmacology and Pharmaceutical Sciences not elsewhere classified
Abstract

Supplemental Material, sj-pdf-9-vet-10.1177_03009858211013712 for International Guidelines for Veterinary Tumor Pathology: A Call to Action by Donald J. Meuten, Frances M. Moore, Taryn A. Donovan, Christof A. Bertram, Robert Klopfleisch, Robert A. Foster, Rebecca C. Smedley, Michael J. Dark, Milan Milovancev, Paul Stromberg, Bruce H. Williams, Marc Aubreville, Giancarlo Avallone, Pompei Bolfa, John Cullen, Michelle M. Dennis, Michael Goldschmidt, Richard Luong, Andrew D. Miller, Margaret A. Miller, John S. Munday, Paola Roccabianca, Elisa N. Salas, F. Yvonne Schulman, Renee Laufer-Amorim, Midori G. Asakawa, Linden Craig, Nick Dervisis, D. Glen Esplin, Jeanne W. George, Marlene Hauck, Yumiko Kagawa, Matti Kiupel, Keith Linder, Kristina Meichner, Laura Marconato, Michelle L. Oblak, Renato L. Santos, R. Mark Simpson, Harold Tvedten and Derick Whitley in Veterinary Pathology

Published
2021
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24. Supplemental Material, sj-pdf-5-vet-10.1177_03009858211013712 - International Guidelines for Veterinary Tumor Pathology: A Call to Action

Author

Meuten, Donald J., Moore, Frances M., Donovan, Taryn A., Bertram, Christof A., Klopfleisch, Robert, Foster, Robert A., Smedley, Rebecca C., Dark, Michael J., Milovancev, Milan, Stromberg, Paul, Williams, Bruce H., Aubreville, Marc, Avallone, Giancarlo, Bolfa, Pompei, Cullen, John, Dennis, Michelle M., Goldschmidt, Michael, Luong, Richard, Miller, Andrew D., Miller, Margaret A., Munday, John S., Roccabianca, Paola, Salas, Elisa N., Schulman, F. Yvonne, Laufer-Amorim, Renee, Asakawa, Midori G., Craig, Linden, Dervisis, Nick, Esplin, D. Glen, George, Jeanne W., Hauck, Marlene, Kagawa, Yumiko, Kiupel, Matti, Linder, Keith, Meichner, Kristina, Marconato, Laura, Oblak, Michelle L., Santos, Renato L., Simpson, R. Mark, Tvedten, Harold, and Whitley, Derick

Subjects
70706 Veterinary Medicine, FOS: Clinical medicine, FOS: Veterinary sciences, 111599 Pharmacology and Pharmaceutical Sciences not elsewhere classified
Abstract

Supplemental Material, sj-pdf-5-vet-10.1177_03009858211013712 for International Guidelines for Veterinary Tumor Pathology: A Call to Action by Donald J. Meuten, Frances M. Moore, Taryn A. Donovan, Christof A. Bertram, Robert Klopfleisch, Robert A. Foster, Rebecca C. Smedley, Michael J. Dark, Milan Milovancev, Paul Stromberg, Bruce H. Williams, Marc Aubreville, Giancarlo Avallone, Pompei Bolfa, John Cullen, Michelle M. Dennis, Michael Goldschmidt, Richard Luong, Andrew D. Miller, Margaret A. Miller, John S. Munday, Paola Roccabianca, Elisa N. Salas, F. Yvonne Schulman, Renee Laufer-Amorim, Midori G. Asakawa, Linden Craig, Nick Dervisis, D. Glen Esplin, Jeanne W. George, Marlene Hauck, Yumiko Kagawa, Matti Kiupel, Keith Linder, Kristina Meichner, Laura Marconato, Michelle L. Oblak, Renato L. Santos, R. Mark Simpson, Harold Tvedten and Derick Whitley in Veterinary Pathology

Published
2021
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25. Supplemental Material, sj-pdf-4-vet-10.1177_03009858211013712 - International Guidelines for Veterinary Tumor Pathology: A Call to Action

Author

Meuten, Donald J., Moore, Frances M., Donovan, Taryn A., Bertram, Christof A., Klopfleisch, Robert, Foster, Robert A., Smedley, Rebecca C., Dark, Michael J., Milovancev, Milan, Stromberg, Paul, Williams, Bruce H., Aubreville, Marc, Avallone, Giancarlo, Bolfa, Pompei, Cullen, John, Dennis, Michelle M., Goldschmidt, Michael, Luong, Richard, Miller, Andrew D., Miller, Margaret A., Munday, John S., Roccabianca, Paola, Salas, Elisa N., Schulman, F. Yvonne, Laufer-Amorim, Renee, Asakawa, Midori G., Craig, Linden, Dervisis, Nick, Esplin, D. Glen, George, Jeanne W., Hauck, Marlene, Kagawa, Yumiko, Kiupel, Matti, Linder, Keith, Meichner, Kristina, Marconato, Laura, Oblak, Michelle L., Santos, Renato L., Simpson, R. Mark, Tvedten, Harold, and Whitley, Derick

Subjects
70706 Veterinary Medicine, FOS: Clinical medicine, FOS: Veterinary sciences, 111599 Pharmacology and Pharmaceutical Sciences not elsewhere classified
Abstract

Supplemental Material, sj-pdf-4-vet-10.1177_03009858211013712 for International Guidelines for Veterinary Tumor Pathology: A Call to Action by Donald J. Meuten, Frances M. Moore, Taryn A. Donovan, Christof A. Bertram, Robert Klopfleisch, Robert A. Foster, Rebecca C. Smedley, Michael J. Dark, Milan Milovancev, Paul Stromberg, Bruce H. Williams, Marc Aubreville, Giancarlo Avallone, Pompei Bolfa, John Cullen, Michelle M. Dennis, Michael Goldschmidt, Richard Luong, Andrew D. Miller, Margaret A. Miller, John S. Munday, Paola Roccabianca, Elisa N. Salas, F. Yvonne Schulman, Renee Laufer-Amorim, Midori G. Asakawa, Linden Craig, Nick Dervisis, D. Glen Esplin, Jeanne W. George, Marlene Hauck, Yumiko Kagawa, Matti Kiupel, Keith Linder, Kristina Meichner, Laura Marconato, Michelle L. Oblak, Renato L. Santos, R. Mark Simpson, Harold Tvedten and Derick Whitley in Veterinary Pathology

Published
2021
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26. Supplemental Material, sj-pdf-6-vet-10.1177_03009858211013712 - International Guidelines for Veterinary Tumor Pathology: A Call to Action

Author

Meuten, Donald J., Moore, Frances M., Donovan, Taryn A., Bertram, Christof A., Klopfleisch, Robert, Foster, Robert A., Smedley, Rebecca C., Dark, Michael J., Milovancev, Milan, Stromberg, Paul, Williams, Bruce H., Aubreville, Marc, Avallone, Giancarlo, Bolfa, Pompei, Cullen, John, Dennis, Michelle M., Goldschmidt, Michael, Luong, Richard, Miller, Andrew D., Miller, Margaret A., Munday, John S., Roccabianca, Paola, Salas, Elisa N., Schulman, F. Yvonne, Laufer-Amorim, Renee, Asakawa, Midori G., Craig, Linden, Dervisis, Nick, Esplin, D. Glen, George, Jeanne W., Hauck, Marlene, Kagawa, Yumiko, Kiupel, Matti, Linder, Keith, Meichner, Kristina, Marconato, Laura, Oblak, Michelle L., Santos, Renato L., Simpson, R. Mark, Tvedten, Harold, and Whitley, Derick

Subjects
70706 Veterinary Medicine, FOS: Clinical medicine, FOS: Veterinary sciences, 111599 Pharmacology and Pharmaceutical Sciences not elsewhere classified
Abstract

Supplemental Material, sj-pdf-6-vet-10.1177_03009858211013712 for International Guidelines for Veterinary Tumor Pathology: A Call to Action by Donald J. Meuten, Frances M. Moore, Taryn A. Donovan, Christof A. Bertram, Robert Klopfleisch, Robert A. Foster, Rebecca C. Smedley, Michael J. Dark, Milan Milovancev, Paul Stromberg, Bruce H. Williams, Marc Aubreville, Giancarlo Avallone, Pompei Bolfa, John Cullen, Michelle M. Dennis, Michael Goldschmidt, Richard Luong, Andrew D. Miller, Margaret A. Miller, John S. Munday, Paola Roccabianca, Elisa N. Salas, F. Yvonne Schulman, Renee Laufer-Amorim, Midori G. Asakawa, Linden Craig, Nick Dervisis, D. Glen Esplin, Jeanne W. George, Marlene Hauck, Yumiko Kagawa, Matti Kiupel, Keith Linder, Kristina Meichner, Laura Marconato, Michelle L. Oblak, Renato L. Santos, R. Mark Simpson, Harold Tvedten and Derick Whitley in Veterinary Pathology

Published
2021
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27. Supplemental Material, sj-pdf-7-vet-10.1177_03009858211013712 - International Guidelines for Veterinary Tumor Pathology: A Call to Action

Author

Meuten, Donald J., Moore, Frances M., Donovan, Taryn A., Bertram, Christof A., Klopfleisch, Robert, Foster, Robert A., Smedley, Rebecca C., Dark, Michael J., Milovancev, Milan, Stromberg, Paul, Williams, Bruce H., Aubreville, Marc, Avallone, Giancarlo, Bolfa, Pompei, Cullen, John, Dennis, Michelle M., Goldschmidt, Michael, Luong, Richard, Miller, Andrew D., Miller, Margaret A., Munday, John S., Roccabianca, Paola, Salas, Elisa N., Schulman, F. Yvonne, Laufer-Amorim, Renee, Asakawa, Midori G., Craig, Linden, Dervisis, Nick, Esplin, D. Glen, George, Jeanne W., Hauck, Marlene, Kagawa, Yumiko, Kiupel, Matti, Linder, Keith, Meichner, Kristina, Marconato, Laura, Oblak, Michelle L., Santos, Renato L., Simpson, R. Mark, Tvedten, Harold, and Whitley, Derick

Subjects
70706 Veterinary Medicine, FOS: Clinical medicine, FOS: Veterinary sciences, 111599 Pharmacology and Pharmaceutical Sciences not elsewhere classified
Abstract

Supplemental Material, sj-pdf-7-vet-10.1177_03009858211013712 for International Guidelines for Veterinary Tumor Pathology: A Call to Action by Donald J. Meuten, Frances M. Moore, Taryn A. Donovan, Christof A. Bertram, Robert Klopfleisch, Robert A. Foster, Rebecca C. Smedley, Michael J. Dark, Milan Milovancev, Paul Stromberg, Bruce H. Williams, Marc Aubreville, Giancarlo Avallone, Pompei Bolfa, John Cullen, Michelle M. Dennis, Michael Goldschmidt, Richard Luong, Andrew D. Miller, Margaret A. Miller, John S. Munday, Paola Roccabianca, Elisa N. Salas, F. Yvonne Schulman, Renee Laufer-Amorim, Midori G. Asakawa, Linden Craig, Nick Dervisis, D. Glen Esplin, Jeanne W. George, Marlene Hauck, Yumiko Kagawa, Matti Kiupel, Keith Linder, Kristina Meichner, Laura Marconato, Michelle L. Oblak, Renato L. Santos, R. Mark Simpson, Harold Tvedten and Derick Whitley in Veterinary Pathology

Published
2021
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28. Supplemental Material, sj-pdf-8-vet-10.1177_03009858211013712 - International Guidelines for Veterinary Tumor Pathology: A Call to Action

Author

Meuten, Donald J., Moore, Frances M., Donovan, Taryn A., Bertram, Christof A., Klopfleisch, Robert, Foster, Robert A., Smedley, Rebecca C., Dark, Michael J., Milovancev, Milan, Stromberg, Paul, Williams, Bruce H., Aubreville, Marc, Avallone, Giancarlo, Bolfa, Pompei, Cullen, John, Dennis, Michelle M., Goldschmidt, Michael, Luong, Richard, Miller, Andrew D., Miller, Margaret A., Munday, John S., Roccabianca, Paola, Salas, Elisa N., Schulman, F. Yvonne, Laufer-Amorim, Renee, Asakawa, Midori G., Craig, Linden, Dervisis, Nick, Esplin, D. Glen, George, Jeanne W., Hauck, Marlene, Kagawa, Yumiko, Kiupel, Matti, Linder, Keith, Meichner, Kristina, Marconato, Laura, Oblak, Michelle L., Santos, Renato L., Simpson, R. Mark, Tvedten, Harold, and Whitley, Derick

Subjects
70706 Veterinary Medicine, FOS: Clinical medicine, FOS: Veterinary sciences, 111599 Pharmacology and Pharmaceutical Sciences not elsewhere classified
Abstract

Supplemental Material, sj-pdf-8-vet-10.1177_03009858211013712 for International Guidelines for Veterinary Tumor Pathology: A Call to Action by Donald J. Meuten, Frances M. Moore, Taryn A. Donovan, Christof A. Bertram, Robert Klopfleisch, Robert A. Foster, Rebecca C. Smedley, Michael J. Dark, Milan Milovancev, Paul Stromberg, Bruce H. Williams, Marc Aubreville, Giancarlo Avallone, Pompei Bolfa, John Cullen, Michelle M. Dennis, Michael Goldschmidt, Richard Luong, Andrew D. Miller, Margaret A. Miller, John S. Munday, Paola Roccabianca, Elisa N. Salas, F. Yvonne Schulman, Renee Laufer-Amorim, Midori G. Asakawa, Linden Craig, Nick Dervisis, D. Glen Esplin, Jeanne W. George, Marlene Hauck, Yumiko Kagawa, Matti Kiupel, Keith Linder, Kristina Meichner, Laura Marconato, Michelle L. Oblak, Renato L. Santos, R. Mark Simpson, Harold Tvedten and Derick Whitley in Veterinary Pathology

Published
2021
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29. Supplemental Material, sj-pdf-10-vet-10.1177_03009858211013712 - International Guidelines for Veterinary Tumor Pathology: A Call to Action

Author

Meuten, Donald J., Moore, Frances M., Donovan, Taryn A., Bertram, Christof A., Klopfleisch, Robert, Foster, Robert A., Smedley, Rebecca C., Dark, Michael J., Milovancev, Milan, Stromberg, Paul, Williams, Bruce H., Aubreville, Marc, Avallone, Giancarlo, Bolfa, Pompei, Cullen, John, Dennis, Michelle M., Goldschmidt, Michael, Luong, Richard, Miller, Andrew D., Miller, Margaret A., Munday, John S., Roccabianca, Paola, Salas, Elisa N., Schulman, F. Yvonne, Laufer-Amorim, Renee, Asakawa, Midori G., Craig, Linden, Dervisis, Nick, Esplin, D. Glen, George, Jeanne W., Hauck, Marlene, Kagawa, Yumiko, Kiupel, Matti, Linder, Keith, Meichner, Kristina, Marconato, Laura, Oblak, Michelle L., Santos, Renato L., Simpson, R. Mark, Tvedten, Harold, and Whitley, Derick

Subjects
70706 Veterinary Medicine, FOS: Clinical medicine, FOS: Veterinary sciences, 111599 Pharmacology and Pharmaceutical Sciences not elsewhere classified
Abstract

Supplemental Material, sj-pdf-10-vet-10.1177_03009858211013712 for International Guidelines for Veterinary Tumor Pathology: A Call to Action by Donald J. Meuten, Frances M. Moore, Taryn A. Donovan, Christof A. Bertram, Robert Klopfleisch, Robert A. Foster, Rebecca C. Smedley, Michael J. Dark, Milan Milovancev, Paul Stromberg, Bruce H. Williams, Marc Aubreville, Giancarlo Avallone, Pompei Bolfa, John Cullen, Michelle M. Dennis, Michael Goldschmidt, Richard Luong, Andrew D. Miller, Margaret A. Miller, John S. Munday, Paola Roccabianca, Elisa N. Salas, F. Yvonne Schulman, Renee Laufer-Amorim, Midori G. Asakawa, Linden Craig, Nick Dervisis, D. Glen Esplin, Jeanne W. George, Marlene Hauck, Yumiko Kagawa, Matti Kiupel, Keith Linder, Kristina Meichner, Laura Marconato, Michelle L. Oblak, Renato L. Santos, R. Mark Simpson, Harold Tvedten and Derick Whitley in Veterinary Pathology

Published
2021
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30. Supplemental Material, sj-pdf-2-vet-10.1177_03009858211013712 - International Guidelines for Veterinary Tumor Pathology: A Call to Action

Author

Meuten, Donald J., Moore, Frances M., Donovan, Taryn A., Bertram, Christof A., Klopfleisch, Robert, Foster, Robert A., Smedley, Rebecca C., Dark, Michael J., Milovancev, Milan, Stromberg, Paul, Williams, Bruce H., Aubreville, Marc, Avallone, Giancarlo, Bolfa, Pompei, Cullen, John, Dennis, Michelle M., Goldschmidt, Michael, Luong, Richard, Miller, Andrew D., Miller, Margaret A., Munday, John S., Roccabianca, Paola, Salas, Elisa N., Schulman, F. Yvonne, Laufer-Amorim, Renee, Asakawa, Midori G., Craig, Linden, Dervisis, Nick, Esplin, D. Glen, George, Jeanne W., Hauck, Marlene, Kagawa, Yumiko, Kiupel, Matti, Linder, Keith, Meichner, Kristina, Marconato, Laura, Oblak, Michelle L., Santos, Renato L., Simpson, R. Mark, Tvedten, Harold, and Whitley, Derick

Subjects
70706 Veterinary Medicine, FOS: Clinical medicine, FOS: Veterinary sciences, 111599 Pharmacology and Pharmaceutical Sciences not elsewhere classified
Abstract

Supplemental Material, sj-pdf-2-vet-10.1177_03009858211013712 for International Guidelines for Veterinary Tumor Pathology: A Call to Action by Donald J. Meuten, Frances M. Moore, Taryn A. Donovan, Christof A. Bertram, Robert Klopfleisch, Robert A. Foster, Rebecca C. Smedley, Michael J. Dark, Milan Milovancev, Paul Stromberg, Bruce H. Williams, Marc Aubreville, Giancarlo Avallone, Pompei Bolfa, John Cullen, Michelle M. Dennis, Michael Goldschmidt, Richard Luong, Andrew D. Miller, Margaret A. Miller, John S. Munday, Paola Roccabianca, Elisa N. Salas, F. Yvonne Schulman, Renee Laufer-Amorim, Midori G. Asakawa, Linden Craig, Nick Dervisis, D. Glen Esplin, Jeanne W. George, Marlene Hauck, Yumiko Kagawa, Matti Kiupel, Keith Linder, Kristina Meichner, Laura Marconato, Michelle L. Oblak, Renato L. Santos, R. Mark Simpson, Harold Tvedten and Derick Whitley in Veterinary Pathology

Published
2021
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31. Supplemental Material, sj-pdf-3-vet-10.1177_03009858211013712 - International Guidelines for Veterinary Tumor Pathology: A Call to Action

Author

Meuten, Donald J., Moore, Frances M., Donovan, Taryn A., Bertram, Christof A., Klopfleisch, Robert, Foster, Robert A., Smedley, Rebecca C., Dark, Michael J., Milovancev, Milan, Stromberg, Paul, Williams, Bruce H., Aubreville, Marc, Avallone, Giancarlo, Bolfa, Pompei, Cullen, John, Dennis, Michelle M., Goldschmidt, Michael, Luong, Richard, Miller, Andrew D., Miller, Margaret A., Munday, John S., Roccabianca, Paola, Salas, Elisa N., Schulman, F. Yvonne, Laufer-Amorim, Renee, Asakawa, Midori G., Craig, Linden, Dervisis, Nick, Esplin, D. Glen, George, Jeanne W., Hauck, Marlene, Kagawa, Yumiko, Kiupel, Matti, Linder, Keith, Meichner, Kristina, Marconato, Laura, Oblak, Michelle L., Santos, Renato L., Simpson, R. Mark, Tvedten, Harold, and Whitley, Derick

Subjects
70706 Veterinary Medicine, FOS: Clinical medicine, FOS: Veterinary sciences, 111599 Pharmacology and Pharmaceutical Sciences not elsewhere classified
Abstract

Supplemental Material, sj-pdf-3-vet-10.1177_03009858211013712 for International Guidelines for Veterinary Tumor Pathology: A Call to Action by Donald J. Meuten, Frances M. Moore, Taryn A. Donovan, Christof A. Bertram, Robert Klopfleisch, Robert A. Foster, Rebecca C. Smedley, Michael J. Dark, Milan Milovancev, Paul Stromberg, Bruce H. Williams, Marc Aubreville, Giancarlo Avallone, Pompei Bolfa, John Cullen, Michelle M. Dennis, Michael Goldschmidt, Richard Luong, Andrew D. Miller, Margaret A. Miller, John S. Munday, Paola Roccabianca, Elisa N. Salas, F. Yvonne Schulman, Renee Laufer-Amorim, Midori G. Asakawa, Linden Craig, Nick Dervisis, D. Glen Esplin, Jeanne W. George, Marlene Hauck, Yumiko Kagawa, Matti Kiupel, Keith Linder, Kristina Meichner, Laura Marconato, Michelle L. Oblak, Renato L. Santos, R. Mark Simpson, Harold Tvedten and Derick Whitley in Veterinary Pathology

Published
2021
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32. International Guidelines for Veterinary Tumor Pathology: A Call to Action

Author

Meuten, Donald J., Moore, Frances M., Donovan, Taryn A., Bertram, Christof A., Klopfleisch, Robert, Foster, Robert A., Smedley, Rebecca C., Dark, Michael J., Milovancev, Milan, Stromberg, Paul, Williams, Bruce H., Aubreville, Marc, Avallone, Giancarlo, Bolfa, Pompei, Cullen, John, Dennis, Michelle M., Goldschmidt, Michael, Luong, Richard, Miller, Andrew D., Miller, Margaret A., Munday, John S., Roccabianca, Paola, Salas, Elisa N., Schulman, F. Yvonne, Laufer-Amorim, Renee, Asakawa, Midori G., Craig, Linden, Dervisis, Nikolaos G., Esplin, D. Glen, George, Jeanne W., Hauck, Marlene, Kagawa, Yumiko, Kiupel, Matti, Linder, Keith, Meichner, Kristina, Marconato, Laura, Oblak, Michelle L., Santos, Renato L., Simpson, R. Mark, Tvedten, Harold, Whitley, Derick, Meuten, Donald J., Moore, Frances M., Donovan, Taryn A., Bertram, Christof A., Klopfleisch, Robert, Foster, Robert A., Smedley, Rebecca C., Dark, Michael J., Milovancev, Milan, Stromberg, Paul, Williams, Bruce H., Aubreville, Marc, Avallone, Giancarlo, Bolfa, Pompei, Cullen, John, Dennis, Michelle M., Goldschmidt, Michael, Luong, Richard, Miller, Andrew D., Miller, Margaret A., Munday, John S., Roccabianca, Paola, Salas, Elisa N., Schulman, F. Yvonne, Laufer-Amorim, Renee, Asakawa, Midori G., Craig, Linden, Dervisis, Nikolaos G., Esplin, D. Glen, George, Jeanne W., Hauck, Marlene, Kagawa, Yumiko, Kiupel, Matti, Linder, Keith, Meichner, Kristina, Marconato, Laura, Oblak, Michelle L., Santos, Renato L., Simpson, R. Mark, Tvedten, Harold, and Whitley, Derick

Abstract

Standardization of tumor assessment lays the foundation for validation of grading systems, permits reproducibility of oncologic studies among investigators, and increases confidence in the significance of study results. Currently, there is minimal methodological standardization for assessing tumors in veterinary medicine, with few attempts to validate published protocols and grading schemes. The current article attempts to address these shortcomings by providing standard guidelines for tumor assessment parameters and protocols for evaluating specific tumor types. More detailed information is available in the Supplemental Files, the intention of which is 2-fold: publication as part of this commentary, but more importantly, these will be available as “living documents” on a website (www.vetcancerprotocols.org), which will be updated as new information is presented in the peer-reviewed literature. Our hope is that veterinary pathologists will agree that this initiative is needed, and will contribute to and utilize this information for routine diagnostic work and oncologic studies. Journal editors and reviewers can utilize checklists to ensure publications include sufficient detail and standardized methods of tumor assessment. To maintain the relevance of the guidelines and protocols, it is critical that the information is periodically updated and revised as new studies are published and validated with the intent of providing a repository of this information. Our hope is that this initiative (a continuation of efforts published in this journal in 2011) will facilitate collaboration and reproducibility between pathologists and institutions, increase case numbers, and strengthen clinical research findings, thus ensuring continued progress in veterinary oncologic pathology and improving patient care.

Published
2021

35. List of Contributors

Author

Bowen, Anna, primary, Batz, Michael B., additional, Caswell, Julie A., additional, Chittiboyina, Amar G., additional, Dark, Michael J., additional, Destro, Maria Teresa, additional, De Waal, Caroline Smith, additional, El-Arabi, Tarek F., additional, Estrada-Garcia, Teresa, additional, Fanning, S., additional, Fortin, Neal D., additional, Franco, A.A., additional, Gastañaduy, Paul A., additional, Glass, Kathleen, additional, Gopinath, G., additional, Grattan, Lynn, additional, Griffin, Patricia M., additional, Griffiths, Mansel W., additional, Grim, Christopher J., additional, Hald, Tine, additional, Hall, Aron J., additional, Harwood, Valerie J., additional, Havelaar, Arie, additional, Hecht, Gail A., additional, Hodges, Kim, additional, Holobaugh, Sailor, additional, Hu, L., additional, Jarvis, K.G., additional, Jones, Melissa, additional, Juneja, V.K., additional, Karlsson, Erik A., additional, Karst, Stephanie M., additional, Khan, Ikhlas A., additional, Kienesberger, Sabine, additional, Kirk, Martyn, additional, Kortbeek, Titia, additional, Kothary, M.H., additional, Labbé, Ronald G., additional, Lammerding, Anna, additional, Landgraf, Mariza, additional, Linton, Richard H., additional, Lopman, Ben A., additional, Marshall, Kristin, additional, McSwane, David Z., additional, Morris, J. Glenn, additional, Nesbakken, Truls, additional, Nygren, Benjamin, additional, Opsteegh, Marieke, additional, Orsi, Renato H., additional, Osman, Ahmed Mohamed Galal, additional, Parashar, Umesh D., additional, Perez-Perez, Guillermo Ignacio, additional, Pitt, John I., additional, Plunkett, David, additional, Potter, Morris E., additional, Richt, Jürgen A., additional, Roberts, Cynthia, additional, Rodriguez, Alfredo C., additional, Sathyamoorthy, V., additional, Scallan, Elaine, additional, Schultz-Cherry, Stacey, additional, Sharapov, Umid M., additional, Tall, B.D., additional, Tarr, Phillip I., additional, Teshale, Eyasu H., additional, van der Giessen, Joke, additional, Vinjé, Jan, additional, Walden, Heather Stockdale, additional, Wang, Siyun, additional, Wright, Anita C., additional, and Young, Alan J., additional

Published
2013
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40. Complete Urogenital and Anorectal Duplication in a Dog

Author

Coffman, Jonathan M., McConkey, Marina, Ellison, Gary, Huynh, Elizabeth, and Dark, Michael J.

Subjects
Article Subject
Abstract

A 10-week-old sexually intact female golden retriever was evaluated for two functional anal openings and a bipartite vulva. Examination revealed haired skin between two separate anatomically smaller anal openings. On rectal palpation, a soft tissue septum (5 cm) with a mucosal surface between the two anal openings was palpated. In addition, circumferential rectal musculature was not appreciated on the ventral aspect. Urogenital evaluation revealed duplication of the vestibule and vagina with a complete centrally located septum extending dorsoventrally. Computed tomography (CT) of the abdomen and pelvis, vaginocystourethrogram, and colonogram were performed. Complete bifurcation of the urinary bladder with duplication of the urethra, cervix, and vaginal canal was noted. Approximately 2 cm from the rectum, there was a similar bifurcation that converged the colon into two rectal portions and separate anal openings. The owner was counseled on the severity of congenital malformations and a high likelihood of aging-related developmental complications in the future. The owner elected humane euthanasia and a necropsy was performed to confirm the malformations.

Published
2019
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41. Comparative genomics and transcriptomics of trait-gene association

Author

Pierlé Sebastián, Dark Michael J, Dahmen Dani, Palmer Guy H, and Brayton Kelly A

Subjects
Bacteria, Rickettsia, SNP, RNA-seq, Anaplasma, Biotechnology, TP248.13-248.65, Genetics, QH426-470
Abstract

Abstract Background The Order Rickettsiales includes important tick-borne pathogens, from Rickettsia rickettsii, which causes Rocky Mountain spotted fever, to Anaplasma marginale, the most prevalent vector-borne pathogen of cattle. Although most pathogens in this Order are transmitted by arthropod vectors, little is known about the microbial determinants of transmission. A. marginale provides unique tools for studying the determinants of transmission, with multiple strain sequences available that display distinct and reproducible transmission phenotypes. The closed core A. marginale genome suggests that any phenotypic differences are due to single nucleotide polymorphisms (SNPs). We combined DNA/RNA comparative genomic approaches using strains with different tick transmission phenotypes and identified genes that segregate with transmissibility. Results Comparison of seven strains with different transmission phenotypes generated a list of SNPs affecting 18 genes and nine promoters. Transcriptional analysis found two candidate genes downstream from promoter SNPs that were differentially transcribed. To corroborate the comparative genomics approach we used three RNA-seq platforms to analyze the transcriptomes from two A. marginale strains with different transmission phenotypes. RNA-seq analysis confirmed the comparative genomics data and found 10 additional genes whose transcription between strains with distinct transmission efficiencies was significantly different. Six regions of the genome that contained no annotation were found to be transcriptionally active, and two of these newly identified transcripts were differentially transcribed. Conclusions This approach identified 30 genes and two novel transcripts potentially involved in tick transmission. We describe the transcriptome of an obligate intracellular bacterium in depth, while employing massive parallel sequencing to dissect an important trait in bacterial pathogenesis.

Published
2012
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47. Conservation in the face of diversity: multistrain analysis of an intracellular bacterium

Author

Knowles Donald P, Palmer Guy H, Nordeen Elizabeth, Gonzales Mikel P, Kappmeyer Lowell S, Herndon David R, Dark Michael J, and Brayton Kelly A

Subjects
Biotechnology, TP248.13-248.65, Genetics, QH426-470
Abstract

Abstract Background With the recent completion of numerous sequenced bacterial genomes, notable advances have been made in understanding the level of conservation between various species. However, relatively little is known about the genomic diversity among strains. We determined the complete genome sequence of the Florida strain of Anaplasma marginale, and near complete (>96%) sequences for an additional three strains, for comparative analysis with the previously fully sequenced St. Maries strain genome. Results These comparisons revealed that A. marginale has a closed-core genome with few highly plastic regions, which include the msp2 and msp3 genes, as well as the aaap locus. Comparison of the Florida and St. Maries genome sequences found that SNPs comprise 0.8% of the longer Florida genome, with 33.5% of the total SNPs between all five strains present in at least two strains and 3.0% of SNPs present in all strains except Florida. Comparison of genomes from three strains of Mycobacterium tuberculosis, Bacillus anthracis, and Nessieria meningiditis, as well as four Chlamydophila pneumoniae strains found that 98.8%–100% of SNPs are unique to each strain, suggesting A. marginale, with 76.0%, has an intermediate level of strain-specific SNPs. Comparison of genomes from other organisms revealed variation in diversity that did not segregate with the environmental niche the bacterium occupies, ranging from 0.00% to 8.00% of the larger pairwise-compared genome. Conclusion Analysis of multiple A. marginale strains suggests intracellular bacteria have more variable SNP retention rates than previously reported, and may have closed-core genomes in response to the host organism environment and/or reductive evolution.

Published
2009
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48. Self-Complementary Adeno-Associated Virus–Mediated Interleukin-1 Receptor Antagonist Gene Delivery for the Treatment of Osteoarthritis: Test of Efficacy in an Equine Model

Author

Watson Levings, Rachael S., primary, Smith, Andrew D., additional, Broome, Ted A., additional, Rice, Brett L., additional, Gibbs, Eric P., additional, Myara, David A., additional, Hyddmark, E. Viktoria, additional, Nasri, Elham, additional, Zarezadeh, Ali, additional, Levings, Padraic P., additional, Lu, Yuan, additional, White, Margaret E., additional, Dacanay, E. Anthony, additional, Foremny, Gregory B., additional, Evans, Christopher H., additional, Morton, Alison J., additional, Winter, Mathew, additional, Dark, Michael J., additional, Nickerson, David M., additional, Colahan, Patrick T., additional, and Ghivizzani, Steven C., additional

Published
2018
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49. Gene Therapy for Osteoarthritis: Pharmacokinetics of Intra-Articular Self-Complementary Adeno-Associated Virus Interleukin-1 Receptor Antagonist Delivery in an Equine Model

Author

Watson Levings, Rachael S., primary, Broome, Ted A., additional, Smith, Andrew D., additional, Rice, Brett L., additional, Gibbs, Eric P., additional, Myara, David A., additional, Hyddmark, E. Viktoria, additional, Nasri, Elham, additional, Zarezadeh, Ali, additional, Levings, Padraic P., additional, Lu, Yuan, additional, White, Margaret E., additional, Dacanay, E. Anthony, additional, Foremny, Gregory B., additional, Evans, Christopher H., additional, Morton, Alison J., additional, Winter, Mathew, additional, Dark, Michael J., additional, Nickerson, David M., additional, Colahan, Patrick T., additional, and Ghivizzani, Steven C., additional

Published
2018
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