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2. Development of a multi‐scanner facility for data acquisition for digital pathology artificial intelligence.

Author

Humphries, Matthew P, Kaye, Danny, Stankeviciute, Gaby, Halliwell, Jacob, Wright, Alexander I, Bansal, Daljeet, Brettle, David, and Treanor, Darren

Subjects
ARTIFICIAL intelligence, MEDICAL protocols, SCANNING systems, DIAGNOSIS, ACQUISITION of data
Abstract

Whole slide imaging (WSI) of pathology glass slides using high‐resolution scanners has enabled the large‐scale application of artificial intelligence (AI) in pathology, to support the detection and diagnosis of disease, potentially increasing efficiency and accuracy in tissue diagnosis. Despite the promise of AI, it has limitations. 'Brittleness' or sensitivity to variation in inputs necessitates that large amounts of data are used for training. AI is often trained on data from different scanners but not usually by replicating the same slide across scanners. The utilisation of multiple WSI instruments to produce digital replicas of the same slides will make more comprehensive datasets and may improve the robustness and generalisability of AI algorithms as well as reduce the overall data requirements of AI training. To this end, the National Pathology Imaging Cooperative (NPIC) has built the AI FORGE (Facilitating Opportunities for Robust Generalisable data Emulation), a unique multi‐scanner facility embedded in a clinical site in the NHS to (1) compare scanner performance, (2) replicate digital pathology image datasets across WSI systems, and (3) support the evaluation of clinical AI algorithms. The NPIC AI FORGE currently comprises 15 scanners from nine manufacturers. It can generate approximately 4,000 WSI images per day (approximately 7 TB of image data). This paper describes the process followed to plan and build such a facility. © 2024 The Author(s). The Journal of Pathology published by John Wiley & Sons Ltd on behalf of The Pathological Society of Great Britain and Ireland. [ABSTRACT FROM AUTHOR]

Published
2024
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3. Activation of a cGAS-STING-mediated immune response predicts response to neoadjuvant chemotherapy in early breast cancer

Author

Parkes, Eileen E., Savage, Kienan I., Lioe, Tong, Boyd, Clinton, Halliday, Sophia, Walker, Steven M., Lowry, Keith, Knight, Laura, Buckley, Niamh E., Grogan, Andrena, Logan, Gemma E., Clayton, Alison, Hurwitz, Jane, Kirk, Stephen J., Xu, Jiamei, Sidi, Fatima Abdullahi, Humphries, Matthew P., Bingham, Victoria, James, Jaqueline A., James, Colin R., Paul Harkin, D., Kennedy, Richard D., and McIntosh, Stuart A.

Published
2022
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4. Male Breast Cancer

Author

Speirs, Valerie, Humphries, Matthew P., Shaaban, Abeer M., van Krieken, J. H. J. M., Series Editor, Sapino, Anna, editor, and Kulka, Janina, editor

Published
2020
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8. Immune status is prognostic for poor survival in colorectal cancer patients and is associated with tumour hypoxia

Author

Craig, Stephanie G., Humphries, Matthew P., Alderdice, Matthew, Bingham, Victoria, Richman, Susan D., Loughrey, Maurice B., Coleman, Helen G., Viratham-Pulsawatdi, Amelie, McCombe, Kris, Murray, Graeme I., Blake, Andrew, Domingo, Enric, Robineau, James, Brown, Louise, Fisher, David, Seymour, Matthew T., Quirke, Phil, Bankhead, Peter, McQuaid, Stephen, Lawler, Mark, McArt, Darragh G., Maughan, Tim S., James, Jacqueline A., and Salto-Tellez, Manuel

Published
2020
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14. Data from Metastasis and Immune Evasion from Extracellular cGAMP Hydrolysis

Author

Li, Jun, primary, Duran, Mercedes A., primary, Dhanota, Ninjit, primary, Chatila, Walid K., primary, Bettigole, Sarah E., primary, Kwon, John, primary, Sriram, Roshan K., primary, Humphries, Matthew P., primary, Salto-Tellez, Manuel, primary, James, Jacqueline A., primary, Hanna, Matthew G., primary, Melms, Johannes C., primary, Vallabhaneni, Sreeram, primary, Litchfield, Kevin, primary, Usaite, Ieva, primary, Biswas, Dhruva, primary, Bareja, Rohan, primary, Li, Hao Wei, primary, Martin, Maria Laura, primary, Dorsaint, Princesca, primary, Cavallo, Julie-Ann, primary, Li, Peng, primary, Pauli, Chantal, primary, Gottesdiener, Lee, primary, DiPardo, Benjamin J., primary, Hollmann, Travis J., primary, Merghoub, Taha, primary, Wen, Hannah Y., primary, Reis-Filho, Jorge S., primary, Riaz, Nadeem, primary, Su, Shin-San Michael, primary, Kalbasi, Anusha, primary, Vasan, Neil, primary, Powell, Simon N., primary, Wolchok, Jedd D., primary, Elemento, Olivier, primary, Swanton, Charles, primary, Shoushtari, Alexander N., primary, Parkes, Eileen E., primary, Izar, Benjamin, primary, and Bakhoum, Samuel F., primary

Published
2023
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15. Supplementary Data PDF from Metastasis and Immune Evasion from Extracellular cGAMP Hydrolysis

Author

Li, Jun, primary, Duran, Mercedes A., primary, Dhanota, Ninjit, primary, Chatila, Walid K., primary, Bettigole, Sarah E., primary, Kwon, John, primary, Sriram, Roshan K., primary, Humphries, Matthew P., primary, Salto-Tellez, Manuel, primary, James, Jacqueline A., primary, Hanna, Matthew G., primary, Melms, Johannes C., primary, Vallabhaneni, Sreeram, primary, Litchfield, Kevin, primary, Usaite, Ieva, primary, Biswas, Dhruva, primary, Bareja, Rohan, primary, Li, Hao Wei, primary, Martin, Maria Laura, primary, Dorsaint, Princesca, primary, Cavallo, Julie-Ann, primary, Li, Peng, primary, Pauli, Chantal, primary, Gottesdiener, Lee, primary, DiPardo, Benjamin J., primary, Hollmann, Travis J., primary, Merghoub, Taha, primary, Wen, Hannah Y., primary, Reis-Filho, Jorge S., primary, Riaz, Nadeem, primary, Su, Shin-San Michael, primary, Kalbasi, Anusha, primary, Vasan, Neil, primary, Powell, Simon N., primary, Wolchok, Jedd D., primary, Elemento, Olivier, primary, Swanton, Charles, primary, Shoushtari, Alexander N., primary, Parkes, Eileen E., primary, Izar, Benjamin, primary, and Bakhoum, Samuel F., primary

Published
2023
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16. supplementary figures, from In-depth Clinical and Biological Exploration of DNA Damage Immune Response as a Biomarker for Oxaliplatin Use in Colorectal Cancer

Author

Malla, Sudhir B., primary, Fisher, David J., primary, Domingo, Enric, primary, Blake, Andrew, primary, Hassanieh, Sylvana, primary, Redmond, Keara L., primary, Richman, Susan D., primary, Youdell, Michael, primary, Walker, Steven M., primary, Logan, Gemma E., primary, Chatzipli, Aikaterina, primary, Amirkhah, Raheleh, primary, Humphries, Matthew P., primary, Craig, Stephanie G., primary, McDermott, Ultan, primary, Seymour, Matthew T., primary, Morton, Dion G., primary, Quirke, Philip, primary, West, Nicholas P., primary, Salto-Tellez, Manuel, primary, Kennedy, Richard D., primary, Johnston, Patrick G., primary, Tomlinson, Ian, primary, Koelzer, Viktor H., primary, Campo, Letitia, primary, Kaplan, Richard S., primary, Longley, Daniel B., primary, Lawler, Mark, primary, Maughan, Timothy S., primary, Brown, Louise C., primary, and Dunne, Philip D., primary

Published
2023
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17. Supplementary Results from In-depth Clinical and Biological Exploration of DNA Damage Immune Response as a Biomarker for Oxaliplatin Use in Colorectal Cancer

Author

Malla, Sudhir B., primary, Fisher, David J., primary, Domingo, Enric, primary, Blake, Andrew, primary, Hassanieh, Sylvana, primary, Redmond, Keara L., primary, Richman, Susan D., primary, Youdell, Michael, primary, Walker, Steven M., primary, Logan, Gemma E., primary, Chatzipli, Aikaterina, primary, Amirkhah, Raheleh, primary, Humphries, Matthew P., primary, Craig, Stephanie G., primary, McDermott, Ultan, primary, Seymour, Matthew T., primary, Morton, Dion G., primary, Quirke, Philip, primary, West, Nicholas P., primary, Salto-Tellez, Manuel, primary, Kennedy, Richard D., primary, Johnston, Patrick G., primary, Tomlinson, Ian, primary, Koelzer, Viktor H., primary, Campo, Letitia, primary, Kaplan, Richard S., primary, Longley, Daniel B., primary, Lawler, Mark, primary, Maughan, Timothy S., primary, Brown, Louise C., primary, and Dunne, Philip D., primary

Published
2023
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18. Experimental workflow from A Case-Matched Gender Comparison Transcriptomic Screen Identifies eIF4E and eIF5 as Potential Prognostic Markers in Male Breast Cancer

Author

Humphries, Matthew P., primary, Sundara Rajan, Sreekumar, primary, Droop, Alastair, primary, Suleman, Charlotte A.B., primary, Carbone, Carmine, primary, Nilsson, Cecilia, primary, Honarpisheh, Hedieh, primary, Cserni, Gabor, primary, Dent, Jo, primary, Fulford, Laura, primary, Jordan, Lee B., primary, Jones, J. Louise, primary, Kanthan, Rani, primary, Litwiniuk, Maria, primary, Di Benedetto, Anna, primary, Mottolese, Marcella, primary, Provenzano, Elena, primary, Shousha, Sami, primary, Stephens, Mark, primary, Walker, Rosemary A., primary, Kulka, Janina, primary, Ellis, Ian O., primary, Jeffery, Margaret, primary, Thygesen, Helene H., primary, Cappelletti, Vera, primary, Daidone, Maria G., primary, Hedenfalk, Ingrid A., primary, Fjällskog, Marie-Louise, primary, Melisi, Davide, primary, Stead, Lucy F., primary, Shaaban, Abeer M., primary, and Speirs, Valerie, primary

Published
2023
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19. Cut-off determination and representative staining profiles for eIF proteins determined by immunohistochemistry from A Case-Matched Gender Comparison Transcriptomic Screen Identifies eIF4E and eIF5 as Potential Prognostic Markers in Male Breast Cancer

Author

Humphries, Matthew P., primary, Sundara Rajan, Sreekumar, primary, Droop, Alastair, primary, Suleman, Charlotte A.B., primary, Carbone, Carmine, primary, Nilsson, Cecilia, primary, Honarpisheh, Hedieh, primary, Cserni, Gabor, primary, Dent, Jo, primary, Fulford, Laura, primary, Jordan, Lee B., primary, Jones, J. Louise, primary, Kanthan, Rani, primary, Litwiniuk, Maria, primary, Di Benedetto, Anna, primary, Mottolese, Marcella, primary, Provenzano, Elena, primary, Shousha, Sami, primary, Stephens, Mark, primary, Walker, Rosemary A., primary, Kulka, Janina, primary, Ellis, Ian O., primary, Jeffery, Margaret, primary, Thygesen, Helene H., primary, Cappelletti, Vera, primary, Daidone, Maria G., primary, Hedenfalk, Ingrid A., primary, Fjällskog, Marie-Louise, primary, Melisi, Davide, primary, Stead, Lucy F., primary, Shaaban, Abeer M., primary, and Speirs, Valerie, primary

Published
2023
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20. Interrogation of Oncomine{trade mark, serif} from A Case-Matched Gender Comparison Transcriptomic Screen Identifies eIF4E and eIF5 as Potential Prognostic Markers in Male Breast Cancer

Author

Humphries, Matthew P., primary, Sundara Rajan, Sreekumar, primary, Droop, Alastair, primary, Suleman, Charlotte A.B., primary, Carbone, Carmine, primary, Nilsson, Cecilia, primary, Honarpisheh, Hedieh, primary, Cserni, Gabor, primary, Dent, Jo, primary, Fulford, Laura, primary, Jordan, Lee B., primary, Jones, J. Louise, primary, Kanthan, Rani, primary, Litwiniuk, Maria, primary, Di Benedetto, Anna, primary, Mottolese, Marcella, primary, Provenzano, Elena, primary, Shousha, Sami, primary, Stephens, Mark, primary, Walker, Rosemary A., primary, Kulka, Janina, primary, Ellis, Ian O., primary, Jeffery, Margaret, primary, Thygesen, Helene H., primary, Cappelletti, Vera, primary, Daidone, Maria G., primary, Hedenfalk, Ingrid A., primary, Fjällskog, Marie-Louise, primary, Melisi, Davide, primary, Stead, Lucy F., primary, Shaaban, Abeer M., primary, and Speirs, Valerie, primary

Published
2023
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21. Supplementary Data from In-depth Clinical and Biological Exploration of DNA Damage Immune Response as a Biomarker for Oxaliplatin Use in Colorectal Cancer

Author

Malla, Sudhir B., primary, Fisher, David J., primary, Domingo, Enric, primary, Blake, Andrew, primary, Hassanieh, Sylvana, primary, Redmond, Keara L., primary, Richman, Susan D., primary, Youdell, Michael, primary, Walker, Steven M., primary, Logan, Gemma E., primary, Chatzipli, Aikaterina, primary, Amirkhah, Raheleh, primary, Humphries, Matthew P., primary, Craig, Stephanie G., primary, McDermott, Ultan, primary, Seymour, Matthew T., primary, Morton, Dion G., primary, Quirke, Philip, primary, West, Nicholas P., primary, Salto-Tellez, Manuel, primary, Kennedy, Richard D., primary, Johnston, Patrick G., primary, Tomlinson, Ian, primary, Koelzer, Viktor H., primary, Campo, Letitia, primary, Kaplan, Richard S., primary, Longley, Daniel B., primary, Lawler, Mark, primary, Maughan, Timothy S., primary, Brown, Louise C., primary, and Dunne, Philip D., primary

Published
2023
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22. Subcellular Epithelial HMGB1 Expression Is Associated with Colorectal Neoplastic Progression, Male Sex, Mismatch Repair Protein Expression, Lymph Node Positivity, and an ‘Immune Cold’ Phenotype Associated with Poor Survival

Author

Porter, Ross J., primary, Murray, Graeme I., additional, Hapca, Sandra, additional, Hay, Andrew, additional, Craig, Stephanie G., additional, Humphries, Matthew P., additional, James, Jacqueline A., additional, Salto-Tellez, Manuel, additional, Brice, Daniel P., additional, Berry, Susan H., additional, and McLean, Mairi H., additional

Published
2023
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24. ICOSeg: Real-Time ICOS Protein Expression Segmentation from Immunohistochemistry Slides Using a Lightweight Conv-Transformer Network

Author

Singh, Vivek Kumar, primary, Sarker, Md. Mostafa Kamal, additional, Makhlouf, Yasmine, additional, Craig, Stephanie G., additional, Humphries, Matthew P., additional, Loughrey, Maurice B., additional, James, Jacqueline A., additional, Salto-Tellez, Manuel, additional, O’Reilly, Paul, additional, and Maxwell, Perry, additional

Published
2022
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26. Activation of a cGAS-STING-mediated immune response predicts response to neoadjuvant chemotherapy in early breast cancer

Author

Parkes, Eileen E, Savage, Kienan I, Lioe, Tong, Boyd, Clinton, Halliday, Sophia, Walker, Steven M, Lowry, Keith, Knight, Laura, Buckley, Niamh E, Grogan, Andrena, Logan, Gemma E, Clayton, Alison, Hurwitz, Jane, Kirk, Stephen J, Xu, Jiamei, Sidi, Fatima Abdullahi, Humphries, Matthew P, Bingham, Victoria, Neo-DDIR Investigators, James, Jaqueline A, James, Colin R, Paul Harkin, D, Kennedy, Richard D, and McIntosh, Stuart A

Abstract

BACKGROUND: The DNA-damage immune-response (DDIR) signature is an immune-driven gene expression signature retrospectively validated as predicting response to anthracycline-based therapy. This feasibility study prospectively evaluates the use of this assay to predict neoadjuvant chemotherapy response in early breast cancer. METHODS: This feasibility study assessed the integration of a novel biomarker into clinical workflows. Tumour samples were collected from patients receiving standard of care neoadjuvant chemotherapy (FEC + /-taxane and anti-HER2 therapy as appropriate) at baseline, mid- and post-chemotherapy. Baseline DDIR signature scores were correlated with pathological treatment response. RNA sequencing was used to assess chemotherapy/response-related changes in biologically linked gene signatures. RESULTS: DDIR signature reports were available within 14 days for 97.8% of 46 patients (13 TNBC, 16 HER2 + ve, 27 ER + HER2-ve). Positive scores predicted response to treatment (odds ratio 4.67 for RCB 0-1 disease (95% CI 1.13-15.09, P = 0.032)). DDIR positivity correlated with immune infiltration and upregulated immune-checkpoint gene expression. CONCLUSIONS: This study validates the DDIR signature as predictive of response to neoadjuvant chemotherapy which can be integrated into clinical workflows, potentially identifying a subgroup with high sensitivity to anthracycline chemotherapy. Transcriptomic data suggest induction with anthracycline-containing regimens in immune restricted, "cold" tumours may be effective for immune priming. TRIAL REGISTRATION: Not applicable (non-interventional study). CRUK Internal Database Number 14232.

Published
2021

27. Orthogonal MET analysis in a population‐representative stage II–III colon cancer cohort: prognostic and potential therapeutic implications

Author

Craig, Stephanie G., primary, Mende, Svenja, additional, Humphries, Matthew P., additional, Bingham, Victoria, additional, Viratham Pulsawatdi, Amélie, additional, Loughrey, Maurice B., additional, Coleman, Helen G., additional, McQuaid, Stephen, additional, Wilson, Richard H., additional, Van Schaeybroeck, Sandra, additional, James, Jacqueline A., additional, and Salto‐Tellez, Manuel, additional

Published
2021
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28. The Potential of Digital Image Analysis to Determine Tumor Cell Content in Biobanked Formalin-Fixed, Paraffin-Embedded Tissue Samples

Author

Greene, Christine, primary, O'Doherty, Edwina, additional, Abdullahi Sidi, Fatima, additional, Bingham, Victoria, additional, Fisher, Natalie C., additional, Humphries, Matthew P., additional, Craig, Stephanie G., additional, Harewood, Louise, additional, McQuaid, Stephen, additional, Lewis, Claire, additional, and James, Jacqueline, additional

Published
2021
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30. HistoClean: Open-source Software for Histological Image Pre-processing and Augmentation to Improve Development of Robust Convolutional Neural Networks

Author

McCombe, Kris D., primary, Craig, Stephanie G., additional, Pulsawatdi, Amélie Viratham, additional, Quezada-Marín, Javier I., additional, Hagan, Matthew, additional, Rajendran, Simon, additional, Humphries, Matthew P., additional, Bingham, Victoria, additional, Salto-Tellez, Manuel, additional, Gault, Richard, additional, and James, Jacqueline A., additional

Published
2021
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31. Technical note on the exploration of COVID-19 in autopsy material

Author

Humphries, Matthew Phillip, Bingham, Victoria, Abdullah Sidi, Fatima, Craig, Stephanie, Lara, Beatrize, El-daly, Hesham, O'Doherty, Nicole, Maxwell, Perry, Lewis, Claire, McQuaid, Stephen, Lyness, James, James, Jacqueline, Snead, David R J, and Salto-Tellez, Manuel

Abstract

Interrogation of immune response in autopsy material from patients with SARS-CoV-2 is potentially significant. We aim to describe a validated protocol for the exploration of the molecular physiopathology of SARS-CoV-2 pulmonary disease using multiplex immunofluorescence (mIF).The application of validated assays for the detection of SARS-CoV-2 in tissues, originally developed in our laboratory in the context of oncology, was used to map the topography and complexity of the adaptive immune response at protein and mRNA levels.SARS-CoV-2 is detectable in situ by protein or mRNA, with a sensitivity that could be in part related to disease stage. In formalin-fixed, paraffin-embedded pneumonia material, multiplex immunofluorescent panels are robust, reliable and quantifiable and can detect topographic variations in inflammation related to pathological processes.Clinical autopsies have relevance in understanding diseases of unknown/complex pathophysiology. In particular, autopsy materials are suitable for the detection of SARS-CoV-2 and for the topographic description of the complex tissue-based immune response using mIF.

Published
2023
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32. Colonic epithelial cathelicidin (LL‐37) expression intensity is associated with progression of colorectal cancer and presence of CD8+ T cell infiltrate

Author

Porter, Ross J, primary, Murray, Graeme I, additional, Alnabulsi, Abdo, additional, Humphries, Matthew P, additional, James, Jacqueline A, additional, Salto‐Tellez, Manuel, additional, Craig, Stephanie G, additional, Wang, Ji M, additional, Yoshimura, Teizo, additional, and McLean, Mairi H, additional

Published
2021
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33. Evolutionary genetic algorithm identifies IL2RB as a potential predictive biomarker for immune-checkpoint therapy in colorectal cancer

Author

Alderdice, Matthew, primary, Craig, Stephanie G, additional, Humphries, Matthew P, additional, Gilmore, Alan, additional, Johnston, Nicole, additional, Bingham, Victoria, additional, Coyle, Vicky, additional, Senevirathne, Seedevi, additional, Longley, Daniel B, additional, Loughrey, Maurice B, additional, McQuaid, Stephen, additional, James, Jacqueline A, additional, Salto-Tellez, Manuel, additional, Lawler, Mark, additional, and McArt, Darragh G, additional

Published
2021
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34. Automated tumour recognition and digital pathology scoring unravels new role for PD-L1 in predicting good outcome in ER-/HER2+ breast cancer

Author

Humphries, Matthew P., Hynes, Sean, Bingham, Victoria, Cougot, Delphine, James, Jacqueline, Patel-Socha, Farah, Parkes, Eileen E., Blayney, Jaine K., O'Rorke, Michael A., Irwin, Gareth W., McArt, Darragh G., Kennedy, Richard D., Mullan, Paul B., McQuaid, Stephen, Salto-Tellez, Manuel, and Buckley, Niamh E.

Subjects
SDG 3 - Good Health and Well-being, Article Subject, lcsh:Neoplasms. Tumors. Oncology. Including cancer and carcinogens, lcsh:RC254-282, Research Article
Abstract

The role of PD-L1 as a prognostic and predictive biomarker is an area of great interest. However, there is a lack of consensus on how to deliver PD-L1 as a clinical biomarker. At the heart of this conundrum is the subjective scoring of PD-L1 IHC in most studies to date. Current standard scoring systems involve separation of epithelial and inflammatory cells and find clinical significance in different percentages of expression, e.g., above or below 1%. Clearly, an objective, reproducible and accurate approach to PD-L1 scoring would bring a degree of necessary consistency to this landscape. Using a systematic comparison of technologies and the application of QuPath, a digital pathology platform, we show that high PD-L1 expression is associated with improved clinical outcome in Triple Negative breast cancer in the context of standard of care (SoC) chemotherapy, consistent with previous findings. In addition, we demonstrate for the first time that high PD-L1 expression is also associated with better outcome in ER- disease as a whole including HER2+ breast cancer. We demonstrate the influence of antibody choice on quantification and clinical impact with the Ventana antibody (SP142) providing the most robust assay in our hands. Through sampling different regions of the tumour, we show that tumour rich regions display the greatest range of PD-L1 expression and this has the most clinical significance compared to stroma and lymphoid rich areas. Furthermore, we observe that both inflammatory and epithelial PD-L1 expression are associated with improved survival in the context of chemotherapy. Moreover, as seen with PD-L1 inhibitor studies, a low threshold of PD-L1 expression stratifies patient outcome. This emphasises the importance of using digital pathology and precise biomarker quantitation to achieve accurate and reproducible scores that can discriminate low PD-L1 expression.

Published
2020

35. Additional file 2 of The adaptive immune and immune checkpoint landscape of neoadjuvant treated esophageal adenocarcinoma using digital pathology quantitation

Author

Humphries, Matthew P., Craig, Stephanie G., Kacprzyk, Rafal, Fisher, Natalie C., Bingham, Victoria, McQuaid, Stephen, Murray, Graeme I., McManus, Damian, Turkington, Richard C., James, Jacqueline, and Salto-Tellez, Manuel

Subjects
Data_FILES
Abstract

Additional file 2: Table S2. R.O.C Cut Offs.

Published
2020
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36. Additional file 4 of The adaptive immune and immune checkpoint landscape of neoadjuvant treated esophageal adenocarcinoma using digital pathology quantitation

Author

Humphries, Matthew P., Craig, Stephanie G., Kacprzyk, Rafal, Fisher, Natalie C., Bingham, Victoria, McQuaid, Stephen, Murray, Graeme I., McManus, Damian, Turkington, Richard C., James, Jacqueline, and Salto-Tellez, Manuel

Subjects
ComputingMethodologies_PATTERNRECOGNITION
Abstract

Additional file 4: Figure S1. Robust digital pathology workflow. Flow diagram demonstrates conceptually the process of biomarker quantification, strict quality control and data validation steps.

Published
2020
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37. Additional file 3 of The adaptive immune and immune checkpoint landscape of neoadjuvant treated esophageal adenocarcinoma using digital pathology quantitation

Author

Humphries, Matthew P., Craig, Stephanie G., Kacprzyk, Rafal, Fisher, Natalie C., Bingham, Victoria, McQuaid, Stephen, Murray, Graeme I., McManus, Damian, Turkington, Richard C., James, Jacqueline, and Salto-Tellez, Manuel

Abstract

Additional file 3: Table S3. Discovery Cohort Multivariate Analysis Excluding TRG 1 and 2 cases.

Published
2020
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39. In-depth Clinical and Biological Exploration of DNA Damage Immune Response as a Biomarker for Oxaliplatin Use in Colorectal Cancer

Author

Malla, Sudhir B., primary, Fisher, David J., additional, Domingo, Enric, additional, Blake, Andrew, additional, Hassanieh, Sylvana, additional, Redmond, Keara L., additional, Richman, Susan D., additional, Youdell, Michael, additional, Walker, Steven M., additional, Logan, Gemma E., additional, Chatzipli, Aikaterina, additional, Amirkhah, Raheleh, additional, Humphries, Matthew P., additional, Craig, Stephanie G., additional, McDermott, Ultan, additional, Seymour, Matthew T., additional, Morton, Dion G., additional, Quirke, Philip, additional, West, Nicholas P., additional, Salto-Tellez, Manuel, additional, Kennedy, Richard D., additional, Johnston, Patrick G., additional, Tomlinson, Ian, additional, Koelzer, Viktor H., additional, Campo, Letitia, additional, Kaplan, Richard S., additional, Longley, Daniel B., additional, Lawler, Mark, additional, Maughan, Timothy S., additional, Brown, Louise C., additional, and Dunne, Philip D., additional

Published
2021
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40. Metastasis and Immune Evasion from Extracellular cGAMP Hydrolysis

Author

Li, Jun, primary, Duran, Mercedes A., additional, Dhanota, Ninjit, additional, Chatila, Walid K., additional, Bettigole, Sarah E., additional, Kwon, John, additional, Sriram, Roshan K., additional, Humphries, Matthew P., additional, Salto-Tellez, Manuel, additional, James, Jacqueline A., additional, Hanna, Matthew G., additional, Melms, Johannes C., additional, Vallabhaneni, Sreeram, additional, Litchfield, Kevin, additional, Usaite, Ieva, additional, Biswas, Dhruva, additional, Bareja, Rohan, additional, Li, Hao Wei, additional, Martin, Maria Laura, additional, Dorsaint, Princesca, additional, Cavallo, Julie-Ann, additional, Li, Peng, additional, Pauli, Chantal, additional, Gottesdiener, Lee, additional, DiPardo, Benjamin J., additional, Hollmann, Travis J., additional, Merghoub, Taha, additional, Wen, Hannah Y., additional, Reis-Filho, Jorge S., additional, Riaz, Nadeem, additional, Su, Shin-San Michael, additional, Kalbasi, Anusha, additional, Vasan, Neil, additional, Powell, Simon N., additional, Wolchok, Jedd D., additional, Elemento, Olivier, additional, Swanton, Charles, additional, Shoushtari, Alexander N., additional, Parkes, Eileen E., additional, Izar, Benjamin, additional, and Bakhoum, Samuel F., additional

Published
2020
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42. Identifying mismatch repair‐deficient colon cancer: near‐perfect concordance between immunohistochemistry and microsatellite instability testing in a large, population‐based series

Author

Loughrey, Maurice B, primary, McGrath, Jason, additional, Coleman, Helen G, additional, Bankhead, Peter, additional, Maxwell, Perry, additional, McGready, Claire, additional, Bingham, Victoria, additional, Humphries, Matthew P, additional, Craig, Stephanie G, additional, McQuaid, Stephen, additional, Salto‐Tellez, Manuel, additional, and James, Jacqueline A, additional

Published
2020
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43. A robust multiplex immunofluorescence and digital pathology workflow for the characterisation of the tumour immune microenvironment

Author

Viratham Pulsawatdi, Amélie, primary, Craig, Stephanie G., additional, Bingham, Victoria, additional, McCombe, Kris, additional, Humphries, Matthew P., additional, Senevirathne, Seedevi, additional, Richman, Susan D., additional, Quirke, Phil, additional, Campo, Leticia, additional, Domingo, Enric, additional, Maughan, Timothy S., additional, James, Jacqueline A., additional, and Salto‐Tellez, Manuel, additional

Published
2020
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47. Critical Appraisal of Programmed Death Ligand 1 Reflex Diagnostic Testing: Current Standards and Future Opportunities

Author

Humphries, Matthew P, McQuaid, Stephen, Craig, Stephanie G, Bingham, Victoria, Maxwell, Perry, Maurya, Manisha, McLean, Fiona, Sampson, James, Higgins, Patricia, Greene, Christine, James, Jacqueline, and Salto-Tellez, Manuel

Abstract

INTRODUCTION: Patient suitability to anti-programmed death ligand 1 (PD-L1) immune checkpoint inhibition is key to the treatment of NSCLC. We present, applied to PD-L1 testing: a comprehensive cross-validation of two immunohistochemistry (IHC) clones; our descriptive experience in diagnostic reflex testing; the concordance of IHC to in situ RNA (RNA-ISH); and application of digital pathology.METHODS: Eight hundred thirteen NSCLC tumor samples collected from 564 diagnostic samples were analyzed prospectively, and 249 diagnostic samples analyzed retrospectively in tissue microarray format. Validated methods for IHC and RNA-ISH were tested in tissue microarrays and full sections and the QuPath system were used for digital pathology analysis.RESULTS: Antibody concordance of clones SP263 and 22C3 validation was 97% to 98% in squamous cell carcinoma and adenocarcinomas, respectively. Clinical NSCLC cases were reported as PD-L1-negative (48%), 1% to 49% (23%), and more than 50% (29%), with differences associated to tissue-type and EGFR status. Comparison of IHC and RNA-ISH was highly concordant in both subgroups. Comparison of digital assessment versus manual assessment was highly concordant. Discrepancies were mostly around the 1% clinical threshold. Challenging IHC interpretation included 1) calculating the total tumor cell denominator and the nature of PD-L1 expressing cell aggregates in cytology samples; 2) peritumoral expression of positive immune cells; 3) calculation of positive tumor percentages around clinical thresholds; and 4) relevance of the 100 malignant cell rule.CONCLUSIONS: Sample type and EGFR status dictate differences in the expected percentage of PD-L1 expression. Analysis of PD-L1 is challenging, and interpretative guidelines are discussed. PD-L1 evaluations by RNA-ISH and digital pathology appear reliable, particularly in adenocarcinomas.

Published
2019

48. Colonic epithelial cathelicidin (LL‐37) expression intensity is associated with progression of colorectal cancer and presence of CD8+ T cell infiltrate.

Author

Porter, Ross J, Murray, Graeme I, Alnabulsi, Abdo, Humphries, Matthew P, James, Jacqueline A, Salto‐Tellez, Manuel, Craig, Stephanie G, Wang, Ji M, Yoshimura, Teizo, and McLean, Mairi H

Subjects
COLORECTAL cancer, T cells, CANCER invasiveness, SKIN permeability, GENDER, CANCER-related mortality
Abstract

Colorectal cancer (CRC) remains a leading cause of cancer mortality. Here, we define the colonic epithelial expression of cathelicidin (LL‐37) in CRC. Cathelicidin exerts pleotropic effects including anti‐microbial and immunoregulatory functions. Genetic knockout of cathelicidin led to increased size and number of colorectal tumours in the azoxymethane‐induced murine model of CRC. We aimed to translate this to human disease. The expression of LL‐37 in a large (n = 650) fully characterised cohort of treatment‐naïve primary human colorectal tumours and 50 matched normal mucosa samples with associated clinical and pathological data (patient age, gender, tumour site, tumour stage [UICC], presence or absence of extra‐mural vascular invasion, tumour differentiation, mismatch repair protein status, and survival to 18 years) was assessed by immunohistochemistry. The biological consequences of LL‐37 expression on the epithelial barrier and immune cell phenotype were assessed using targeted quantitative PCR gene expression of epithelial permeability (CLDN2, CLDN4, OCLN, CDH1, and TJP1) and cytokine (IL‐1β, IL‐18, IL‐33, IL‐10, IL‐22, and IL‐27) genes in a human colon organoid model, and CD3+, CD4+, and CD8+ lymphocyte phenotyping by immunohistochemistry, respectively. Our data reveal that loss of cathelicidin is associated with human CRC progression, with a switch in expression intensity an early feature of CRC. LL‐37 expression intensity is associated with CD8+ T cell infiltrate, influenced by tumour characteristics including mismatch repair protein status. There was no effect on epithelial barrier gene expression. These data offer novel insights into the contribution of LL‐37 to the pathogenesis of CRC and as a therapeutic molecule. [ABSTRACT FROM AUTHOR]

Published
2021
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49. Automated Tumour Recognition and Digital Pathology Scoring Unravels New Role for PD-L1 in Predicting Good Outcome in ER-/HER2+ Breast Cancer

Author

Humphries, Matthew P., primary, Hynes, Sean, additional, Bingham, Victoria, additional, Cougot, Delphine, additional, James, Jacqueline, additional, Patel-Socha, Farah, additional, Parkes, Eileen E., additional, Blayney, Jaine K., additional, O’Rorke, Michael A., additional, Irwin, Gareth W., additional, McArt, Darragh G., additional, Kennedy, Richard D., additional, Mullan, Paul B., additional, McQuaid, Stephen, additional, Salto-Tellez, Manuel, additional, and Buckley, Niamh E., additional

Published
2018
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50. Identifying mismatch repair‐deficient colon cancer: near‐perfect concordance between immunohistochemistry and microsatellite instability testing in a large, population‐based series.

Author

Loughrey, Maurice B, McGrath, Jason, Coleman, Helen G, Bankhead, Peter, Maxwell, Perry, McGready, Claire, Bingham, Victoria, Humphries, Matthew P, Craig, Stephanie G, McQuaid, Stephen, Salto‐Tellez, Manuel, and James, Jacqueline A

Subjects
COLON cancer, HISTOCHEMISTRY, MICROSATELLITE repeats, DNA mismatch repair, HEREDITARY nonpolyposis colorectal cancer, IMMUNOHISTOCHEMISTRY, POLYMERASE chain reaction
Abstract

Aims: Establishing the mismatch repair (MMR) status of colorectal cancers is important to enable the detection of underlying Lynch syndrome and inform prognosis and therapy. Current testing typically involves either polymerase chain reaction (PCR)‐based microsatellite instability (MSI) testing or MMR protein immunohistochemistry (IHC). The aim of this study was to compare these two approaches in a large, population‐based cohort of stage 2 and 3 colon cancer cases in Northern Ireland. Methods and results: The study used the Promega pentaplex assay to determine MSI status and a four‐antibody MMR IHC panel. IHC was applied to tumour tissue microarrays with triplicate tumour sampling, and assessed manually. Of 593 cases with available MSI and MMR IHC results, 136 (22.9%) were MSI‐high (MSI‐H) and 135 (22.8%) showed abnormal MMR IHC. Concordance was extremely high, with 97.1% of MSI‐H cases showing abnormal MMR IHC, and 97.8% of cases with abnormal IHC showing MSI‐H status. Under‐representation of tumour epithelial cells in samples from heavily inflamed tumours resulted in misclassification of several cases with abnormal MMR IHC as microsatellite‐stable. MMR IHC revealed rare cases with unusual patterns of MMR protein expression, unusual combinations of expression loss, or secondary clonal loss of expression, as further illustrated by repeat immunostaining on whole tissue sections. Conclusions: MSI PCR testing and MMR IHC can be considered to be equally proficient tests for establishing MMR/MSI status, when there is awareness of the potential pitfalls of either method. The choice of methodology may depend on available services and expertise. [ABSTRACT FROM AUTHOR]

Published
2021
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