Review
Oncology
Romain Cohen, Raphael Colle, Thomas Pudlarz, Maximilien Heran, Alex Duval, Magali Svrcek, Thierry Andre
Summary: Microsatellite instability (MSI) is a tumor phenotype related to a deficient DNA mismatch repair system (dMMR). This phenotype, observed in 5% of metastatic mCRC but 10-18% of localized CRC, is associated with high tumor mutational burden with highly immunogenic neoantigens. It has emerged as a major predictive biomarker for the efficacy of ICIs.
Review
Oncology
Shuangshuang Zhao, Lingli Chen, Yuqin Zang, Wenlu Liu, Shiqi Liu, Fei Teng, Fengxia Xue, Yingmei Wang
Summary: Lynch syndrome (LS) is caused by germline pathogenic variants in mismatch repair (MMR) genes, leading to LS-associated endometrial cancer (LS-EC) which has specific clinicopathologic features. Screening, diagnosis, surveillance, prevention and treatment for LS-EC have significantly advanced, with recommendations for universal LS screening among EC patients.
INTERNATIONAL JOURNAL OF CANCER
(2022)
Article
Oncology
Yan Li, Lihong Fan, Jianming Zheng, Xiu Nie, Yu Sun, Qin Feng, Shenyi Lian, Wenqi Bai, Weijing Cai, Yanan Yang, Bo Su, Yanfeng Xi, Dongmei Lin
Summary: This study systematically investigated the pre-screening methods and characterized the genetic and clinical features of Lynch syndrome (LS) colorectal cancers (CRCs) in Asia. The results demonstrated that MMR IHC and MSI testing were effective methods for LS pre-screening and identified previously unreported pathogenic germline variants of MMR genes in LS patients.
CANCER BIOLOGY & MEDICINE
(2022)
Article
Oncology
Yurong Song, Travis D. Kerr, Chelsea Sanders, Lisheng Dai, Shaneen S. Baxter, Brandon Somerville, Ryan N. Baugher, Stephanie D. Mellott, Todd B. Young, Heidi E. Lawhorn, Teri M. Plona, Bingfang Xu, Lei Wei, Qiang Hu, Song Liu, Alan Hutson, Baktiar Karim, Sandra Burkett, Simone Difilippantonio, Ligia Pinto, Johannes Gebert, Matthias Kloor, Steven M. Lipkin, Shizuko Sei, Robert H. Shoemaker
Summary: This study established organoids with MSI-H characteristics for studying MMR-deficient cancer biology and developed an orthotopic model suitable for evaluating the efficacy of neoantigen-based vaccines or anticancer drugs.
FRONTIERS IN ONCOLOGY
(2023)
Article
Genetics & Heredity
Gaelle Tachon, Arnaud Chong-Si-Tsaon, Thierry Lecomte, Audelaure Junca, Eric Frouin, Elodie Miquelestorena-Standley, Julie Godet, Camille Evrard, Violaine Randrian, Romain Chautard, Marie-Luce Auriault, Valerie Moulin, Serge Guyetant, Gaelle Fromont, Lucie Karayan-Tapon, David Tougeron
Summary: The determination of microsatellite instability (MSI) and deficient mismatch repair (dMMR) in colorectal cancer (CRC) has important implications for management. This study evaluated the interest of HSP110 deletion/expression as a diagnostic tool for dMMR/MSI CRCs and a predictive tool for adjuvant chemotherapy efficacy. The results showed a strong correlation between HSP110 protein expression and the size of HSP110 T-17 deletion in MSI CRCs. HSP110 T-17 deletion was found to be an interesting marker for identifying discordant cases between MMR IHC and MSI.
FRONTIERS IN GENETICS
(2022)
Article
Cell Biology
F. Grillo, M. Paudice, A. Gambella, S. Bozzano, S. Sciallero, A. Puccini, S. Lastraioli, M. Dono, P. Parente, A. Vanoli, V. Angerilli, M. Fassan, L. Mastracci
Summary: This study aims to identify the advantages, disadvantages, and potential pitfalls of MMR evaluation on biopsy tissue for colorectal cancer. The results show that biopsy specimens often have indeterminate stains, particularly for MLH1. However, this issue can be solved by reducing primary incubation times, allowing for accurate assessment of MMR status.
HISTOCHEMISTRY AND CELL BIOLOGY
(2023)
Article
Oncology
Koen Zwart, Frederieke H. van Der Baan, Romain Cohen, Thomas Aparicio, Christelle de la Fouchardiere, Thierry Lecomte, Cornelis J. A. Punt, David Sefrioui, Rik J. Verheijden, Geraldine R. Vink, G. Emerens Wensink, Aziz Zaanan, Miriam Koopman, David Tougeron, Jeanine M. L. Roodhart
Summary: Current knowledge on prognostic biomarkers in metastatic colorectal cancer (mCRC) is mainly based on mCRC patients with pMMR tumors. It is uncertain whether these biomarkers have the same prognostic value in mCRC patients with dMMR tumors.
Article
Oncology
Zhiyu Li, Bo Cheng, Shan Liu, Shanshan Ding, Jinhong Liu, Lanju Quan, Yanjiao Hao, Lin Xu, Huan Zhao, Jing Guo, Suozhu Sun
Summary: The non-classical phenotypes of mismatch repair deficiency (dMMR) and microsatellite instability (MSI) are observed in patients with Lynch syndrome.
FRONTIERS IN ONCOLOGY
(2022)
Review
Immunology
Jiao-Ting Chen, Yu-Wen Zhou, Ting-Rui Han, Jun-Lun Wei, Meng Qiu
Summary: Surgical resection is essential for achieving good prognoses in colorectal cancer (CRC), but some patients fail to meet surgical indications or achieve pathological complete response after surgery. Perioperative therapy can effectively decrease tumor staging and reduce recurrence and metastasis. Immune checkpoint inhibitors (ICIs) have shown satisfactory efficacy and safety in patients with high microsatellite instability/deficient mismatch repair (MSI-H/dMMR), while the therapeutic effect is minimal in patients with mismatch repair-proficient or microsatellite stable (pMMR/MSS). Additional predictors are needed to screen patients with potential clinical benefits. Different combinations of immunotherapy in perioperative clinical trials for CRC have been comprehensively summarized in this review, focusing on efficacy and safety, and pointing out future directions.
FRONTIERS IN IMMUNOLOGY
(2023)
Article
Biochemistry & Molecular Biology
Vitaly Shubin, Yury Shelygin, Sergey Achkasov, Oleg Sushkov, Ilya Nazarov, Alexey Ponomarenko, Iuliia Alimova, Anna Loginova, Aleksey Tsukanov
Summary: The aim of this study was to determine the characteristics of Russian patients with microsatellite instability (MSI) tumors. The results showed that patients with MSI tumors differed in the age of diagnosis, tumor localization, time of cancer recurrence, and stage of the disease. Patients whose tumors had MSI status had higher overall and disease-free survival rates.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2022)
Article
Oncology
Dung T. Le, Luis A. Diaz Jr, Tae Won Kim, Eric Van Cutsem, Ravit Geva, Dirk Jaeger, Hiroki Hara, Matthew Burge, Bert H. O'Neil, Petr Kavan, Takayuki Yoshino, Rosine Guimbaud, Hiroya Taniguchi, Elena Elez, Salah-Eddin Al-Batran, Patrick M. Boland, Yi Cui, Pierre Leconte, Patricia Marinello, Thierry Andre
Summary: The study demonstrated that Pembrolizumab had durable clinical benefit and manageable safety in previously treated MSI-H/dMMR colorectal cancer patients. It showed persistent antitumor activity, prolonged overall survival, and tolerable safety profile.
EUROPEAN JOURNAL OF CANCER
(2023)
Article
Oncology
Daniele Fanale, Lidia Rita Corsini, Chiara Brando, Alessandra Dimino, Clarissa Filorizzo, Luigi Magrin, Roberta Sciacchitano, Alessia Fiorino, Tancredi Didier Bazan Russo, Valentina Calo, Juan Lucio Iovanna, Edoardo Francini, Antonio Russo, Viviana Bazan
Summary: Lynch syndrome is a genetic condition associated with an increased predisposition to colorectal cancer and other tumors. The most efficient strategy to identify patients with this syndrome is still unclear. A study found that analyzing tissue microsatellite instability according to the revised Bethesda guidelines is the best selection approach, but using different selection methods as complementary strategies helps reduce underdiagnosis.
FRONTIERS IN ONCOLOGY
(2022)
Review
Immunology
Wei-Jian Mei, Mi Mi, Jing Qian, Nan Xiao, Ying Yuan, Pei-Rong Ding
Summary: Colorectal cancers with high microsatellite instability and deficient mismatch repair have different characteristics compared to normal CRC, but the testing rates for MSI and MMR remain low in clinical practice. Insufficient testing fails to identify patients with these types of CRC who could benefit from immunotherapy. Understanding the importance of MMR/MSI status in the clinical characteristics and prognosis of CRC may help improve testing rates and guide the development of more effective therapies.
FRONTIERS IN IMMUNOLOGY
(2022)
Article
Gastroenterology & Hepatology
C. Richard Boland, Minoru Koi, Mary T. Hawn, John M. Carethers, Matthew B. Yurgelun
Summary: The scientists in this study have witnessed the development of colorectal cancer research and the understanding of tumor pathogenesis, from early pathological descriptions to personalized therapies. These discoveries have led to a better understanding of the DNA mismatch repair system and the development of immune checkpoint inhibitors, which have transformed and cured certain types of cancers. The study also emphasizes the importance of careful experimentation, perseverance, and thinking outside established paradigms in scientific progress.
DIGESTIVE DISEASES AND SCIENCES
(2023)
Article
Pathology
Chung-Ta Lee, Nan-Haw Chow, Yi-Lin Chen, Chung-Liang Ho, Yu-Min Yeh, Shao-Chieh Lin, Peng-Chan Lin, Bo-Wen Lin, Chien-An Chu, Hung-Wen Tsai, Jenq-Chang Lee
Summary: Microsatellite instability (MSI) in colorectal cancers (CRCs) is associated with mismatch repair system deficiencies, particularly due to methylation of MMR genes and BRAF mutations. Different patterns of dMMR were found to be associated with specific clinicopathological features, with BRAF V600E mutations predominantly occurring in certain types. The expression patterns of MMR proteins also showed distinct associations with tumor staging and age at diagnosis.
PATHOLOGY RESEARCH AND PRACTICE
(2021)
Review
Oncology
Mary Kay Washington, Richard M. Goldberg, George J. Chang, Paul Limburg, Alfred K. Lam, Manuel Salto-Tellez, Mark J. Arends, Iris D. Nagtegaal, David S. Klimstra, Massimo Rugge, Peter Schirmacher, Alexander J. Lazar, Robert D. Odze, Fatima Carneiro, Masashi Fukayama, Ian A. Cree
Summary: The WHO Classification of Tumours provides international standards for classification and diagnosis, with the latest fifth edition going digital and including a series of books. This article summarizes major diagnostic innovations from the past decade that have been incorporated into the classification.
INTERNATIONAL JOURNAL OF CANCER
(2021)
Article
Pathology
Lisa Browning, Eve Fryer, Derek Roskell, Kieron White, Richard Colling, Jens Rittscher, Clare Verrill
Summary: The COVID-19 pandemic has put pressure on our diagnostic services, and the use of digital pathology is on the rise globally, playing a role in maintaining diagnostic practices.
JOURNAL OF CLINICAL PATHOLOGY
(2021)
Review
Pathology
Lisa Browning, Richard Colling, Emad Rakha, Nasir Rajpoot, Jens Rittscher, Jacqueline A. James, Manuel Salto-Tellez, David R. J. Snead, Clare Verrill
Summary: The measures to control COVID-19 outbreak will likely continue until a suitable vaccine or treatment is found, impacting clinical services and research, with pathologists working remotely and changes to protocols and studies. Digital pathology and artificial intelligence may play a key role in safeguarding clinical services and pathology-based research in the current and future climate.
JOURNAL OF CLINICAL PATHOLOGY
(2021)
Article
Oncology
Sudhir B. Malla, David J. Fisher, Enric Domingo, Andrew Blake, Sylvana Hassanieh, Keara L. Redmond, Susan D. Richman, Michael Youdell, Steven M. Walker, Gemma E. Logan, Aikaterina Chatzipli, Raheleh Amirkhah, Matthew P. Humphries, Stephanie G. Craig, Ultan McDermott, Matthew T. Seymour, Dion G. Morton, Philip Quirke, Nicholas P. West, Manuel Salto-Tellez, Richard D. Kennedy, Patrick G. Johnston, Ian Tomlinson, Viktor H. Koelzer, Letitia Campo, Richard S. Kaplan, Daniel B. Longley, Mark Lawler, Timothy S. Maughan, Louise C. Brown, Philip D. Dunne
Summary: Positivity of DDIR does not predict improved response to oxaliplatin treatment in colorectal cancer, with DDIR-negative patients showing a trend towards better outcomes. The DDIR assay may have potential in identifying immune-rich tumors that could benefit from immune checkpoint blockade therapies, beyond the current use of MSI status.
CLINICAL CANCER RESEARCH
(2021)
Article
Oncology
Jun Li, Mercedes A. Duran, Ninjit Dhanota, Walid K. Chatila, Sarah E. Bettigole, John Kwon, Roshan K. Sriram, Matthew P. Humphries, Manuel Salto-Tellez, Jacqueline A. James, Matthew G. Hanna, Johannes C. Melms, Sreeram Vallabhaneni, Kevin Litchfield, Ieva Usaite, Dhruva Biswas, Rohan Bareja, Hao Wei Li, Maria Laura Martin, Princesca Dorsaint, Julie-Ann Cavallo, Peng Li, Chantal Pauli, Lee Gottesdiener, Benjamin J. DiPardo, Travis J. Hollmann, Taha Merghoub, Hannah Y. Wen, Jorge S. Reis-Filho, Nadeem Riaz, Shin-San Michael Su, Anusha Kalbasi, Neil Vasan, Simon N. Powell, Jedd D. Wolchok, Olivier Elemento, Charles Swanton, Alexander N. Shoushtari, Eileen E. Parkes, Benjamin Izar, Samuel F. Bakhoum
Summary: ENPP1 promotes metastasis by degrading cGAMP, inhibiting immune cell infiltration, increasing metastatic potential, and inducing resistance to immunotherapy in chromosomally unstable tumors.
Article
Oncology
Fatima Abdullahi Sidi, Victoria Bingham, Stephanie G. Craig, Stephen McQuaid, Jacqueline James, Matthew P. Humphries, Manuel Salto-Tellez
Summary: The study demonstrates the usefulness of advanced computer software in helping pathologists assess routine tests for immunotherapy treatment. Multiplex testing can provide specific information from patient samples. The use of multiplex immunofluorescence and digital image analysis is effective in quantifying PD-L1 in non-small cell lung cancer and supports clinical workflows.
Article
Biochemistry & Molecular Biology
M. P. Humphries, P. Maxwell, M. Salto-Tellez
Summary: QuPath, created at Queen's University Belfast, is the most widely used image analysis software program globally, addressing various needs in tissue-based image analysis and serving as the system of choice for researchers in scientific research.
COMPUTATIONAL AND STRUCTURAL BIOTECHNOLOGY JOURNAL
(2021)
Article
Gastroenterology & Hepatology
Jonathan W. J. Lee, Feng Zhu, Supriya Srivastava, Stephen Kk Tsao, Christopher Khor, Khek Yu Ho, Kwong Ming Fock, Wee Chian Lim, Tiing Leong Ang, Wan Cheng Chow, Jimmy Bok Yan So, Calvin J. Koh, Shijia Joy Chua, Andrew S. Y. Wong, Jaideepraj Rao, Lee Guan Lim, Khoon Lin Ling, Chung-King Chia, Choon Jin Ooi, Andrea Rajnakova, Wai Ming Yap, Manuel Salto-Tellez, Bow Ho, Richie Soong, Kee Seng Chia, Yik Ying Teo, Ming Teh, Khay-Guan Yeoh
Summary: This study found that gastric intestinal metaplasia (IM) is a significant risk factor for early gastric neoplasia (EGN) in regions with low-intermediate incidence of gastric cancer. Based on the results, it is recommended that high-risk patients (OLGIM III-IV) undergo endoscopic surveillance every 2 years, and intermediate-risk patients (OLGIM II) every 5 years.
Article
Pathology
Ross J. Porter, Graeme Murray, Abdo Alnabulsi, Matthew P. Humphries, Jacqueline A. James, Manuel Salto-Tellez, Stephanie G. Craig, Ji M. Wang, Teizo Yoshimura, Mairi H. McLean
Summary: Research reveals that loss of cathelicidin is associated with human CRC progression, with a switch in expression intensity as an early feature. LL-37 expression intensity is linked to CD8(+) T cell infiltrate and influenced by tumor characteristics.
JOURNAL OF PATHOLOGY CLINICAL RESEARCH
(2021)
Article
Pathology
Abdo Alnabulsi, Tiehui Wang, Wei Pang, Marius Ionescu, Stephanie G. Craig, Matthew P. Humphries, Kris McCombe, Manuel Salto Tellez, Ayham Alnabulsi, Graeme Murray
Summary: A study developed an effective methodology to identify optimal biomarker combinations for the prognosis of colorectal carcinoma. Six biomarkers were identified as the best combination in terms of prognostic power, and it was significantly associated with overall survival and independent of other clinicopathological parameters. The study also demonstrated the potential of this methodology for biomarker discovery in various biological and clinical studies.
JOURNAL OF PATHOLOGY CLINICAL RESEARCH
(2022)
Article
Oncology
Vivek Kumar Singh, Md Mostafa Kamal Sarker, Yasmine Makhlouf, Stephanie G. Craig, Matthew P. Humphries, Maurice B. Loughrey, Jacqueline A. James, Manuel Salto-Tellez, Paul O'Reilly, Perry Maxwell
Summary: In this study, a lightweight deep learning model called ICOSeg is proposed to accurately segment the immune-checkpoint biomarker ICOS protein in colon cancer immunohistochemistry slide patches. The proposed model utilizes a convolutional neural network and transformer to extract relevant features from immunohistochemistry images and performs segmentation using an encoder and decoder sub-network. Experimental results show that ICOSeg achieves better segmentation results compared to existing methods with a reduction in parameters.
Article
Pathology
Matthew Phillip Humphries, Victoria Bingham, Fatima Abdullah Sidi, Stephanie Craig, Beatrize Lara, Hesham El-daly, Nicole O'Doherty, Perry Maxwell, Claire Lewis, Stephen McQuaid, James Lyness, Jacqueline James, David R. J. Snead, Manuel Salto-Tellez
Summary: In this study, a validated protocol using multiplex immunofluorescence (mIF) was described for the exploration of the molecular physiopathology of SARS-CoV-2 pulmonary disease. Validated assays originally developed for the detection of SARS-CoV-2 in tissues were applied to map the adaptive immune response at protein and mRNA levels. The mIF panels showed robust, reliable, and quantifiable performance in detecting topographic variations in inflammation related to pathological processes in formalin-fixed, paraffin-embedded pneumonia material.
JOURNAL OF CLINICAL PATHOLOGY
(2023)
Editorial Material
Oncology
Manuel Salto-Tellez, Jorge S. Reis-Filho
Review
Biochemistry & Molecular Biology
Alice Geaney, Paul O'Reilly, Perry Maxwell, Jacqueline A. James, Darragh Mcart, Manuel Salto-Tellez
Summary: Digital pathology and artificial intelligence have transformed oncology research and cancer diagnostics, allowing for better interpretation of pathology images and improved quantitation of biomarkers. Different approaches of artificial intelligence can solve various problems in pathology workflows and have the potential to revolutionize clinical trials and create complex biomarkers for cancer patients.
Article
Biochemistry & Molecular Biology
Kris D. McCombe, Stephanie G. Craig, Amelie Viratham Pulsawatdi, Javier I. Quezada-Marin, Matthew Hagan, Simon Rajendran, Matthew P. Humphries, Victoria Bingham, Manuel Salto-Tellez, Richard Gault, Jacqueline A. James
Summary: The growth of digital pathology has led to advancements in cancer prediction and prognosis research through the use of deep learning and computer vision techniques. HistoClean, a user-friendly application, aims to improve deep learning models by providing transparent image pre-processing and augmentation techniques.
COMPUTATIONAL AND STRUCTURAL BIOTECHNOLOGY JOURNAL
(2021)