Article
Cell Biology
James Wei Tatt Toh, Puneet Singh, Venkata A. A. S. K. Tangirala, Alex Limmer, Kevin J. Spring
Summary: This study developed a simple, cost-effective, and accurate MSI testing method based on CGE for colorectal cancer classification, successfully distinguishing MSI-L from MSI-H and MSS. An automated computational algorithm for MSI status determination was also created.
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
Maria Rasmussen, Peter Sowter, Richard Gallon, Jon Ambaek Durhuus, Christine Hayes, Ove Andersen, Mef Nilbert, Lone Schejbel, Estrid Hogdall, Mauro Santibanez-Koref, Michael S. Jackson, John Burn, Christina Therkildsen
Summary: This study compared methods of testing for MMR deficiency in Lynch syndrome-associated urothelial cancers. The results showed that Lynch syndrome-associated urothelial cancers frequently had loss of MMR protein expression. Testing for MMR deficiency using immunohistochemistry and/or sequencing-based MSI analysis of sensitive markers offers a potentially useful approach to identifying Lynch syndrome cases.
FRONTIERS IN ONCOLOGY
(2023)
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
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
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
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
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
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
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
Gastroenterology & Hepatology
James W. T. Toh, Kevin Phan, Faizur Reza, Pierre Chapuis, Kevin J. Spring
Summary: Microsatellite instability (MSI-H) in colorectal cancer is associated with improved overall survival and lower rate of dissemination, particularly in stage II and III patients. However, MSI-H does not serve as a robust prognostic marker in stage I or stage IV colorectal cancer without immunotherapy.
INTERNATIONAL JOURNAL OF COLORECTAL DISEASE
(2021)
Article
Pathology
Anne-Sophie van der Werf-'t, Diantha Terlouw, Carli M. Tops, Merel S. van Kan, Liselotte P. van Hest, Hans J. P. Gille, Floor A. M. Duijkers, Anja Wagner, Ellis L. Eikenboom, Tom G. W. Letteboer, Mirjam M. de Jong, Sanne W. Bajwa-ten Broeke, Fonnet E. Bleeker, Encarna B. Gomez Garcia, Niels de Wind, J. Tom van Wezel, Hans Morreau, Manon Suerink, Maartje Nielsen
Summary: This study aimed to identify the various causes of the discordant phenotypes in MSH6-associated Lynch syndrome, including abnormal immunohistochemical staining and mutations in the mismatch repair genes. The results suggest that genetic analysis should be considered in colorectal cancer patients with a strong family history.
Article
Oncology
Anna Plotkin, Ekaterina Olkhov-Mitsel, Sharon Nofech-Mozes
Summary: MLH1 promoter hypermethylation is a common cause of mismatch repair deficiency in endometrial cancer. This study examined the proportion of MLH1-deficient endometrial cancer cases with hypermethylation, assessed the impact of reflex MLH1-PHM testing strategy, and evaluated the associated costs. The results showed that MLH1 hypermethylation is prevalent in endometrial cancer and reflex testing incurs substantial costs. The study suggests the need to optimize resource utilization and testing approaches in healthcare systems with finite resources.
Article
Pathology
Ying-Chun Lo, Christina Price, Kim Blenman, Pallavi Patil, Xuchen Zhang, Marie E. Robert
Summary: Studies have found that colonic biopsy specimens from CPI patients showed significantly lower chronicity scores and similar activity scores compared with patients with IBD. There were differences in the expression of immune cells between CPI colitis and IBD. CD8/FoxP3 ratios may predict therapeutic response in CPI-associated colitis.
AMERICAN JOURNAL OF CLINICAL PATHOLOGY
(2021)
Editorial Material
Medicine, General & Internal
Shana E. Gleeson, Xuchen Zhang, Marwan M. Azar
Summary: This case study presents a 28-year-old man who developed intermittent diarrhea and hematochezia after swimming in the upper Nile River in Uganda. Colonoscopy with biopsy showed rectal granulomas containing oval-shaped features with lateral spines. Treatment plan was not mentioned.
JAMA-JOURNAL OF THE AMERICAN MEDICAL ASSOCIATION
(2021)
Article
Biochemistry & Molecular Biology
Vipin Rawat, Parmanand Malvi, Deborah Della Manna, Eddy S. Yang, Suresh Bugide, Xuchen Zhang, Romi Gupta, Narendra Wajapeyee
Summary: Metabolic deregulation in cancer cells promotes tumor growth and metastasis. In this study, PSPH, a key enzyme in serine metabolism pathway, was found to be upregulated in melanoma samples. Knocking down PSPH resulted in inhibition of melanoma growth and metastasis through suppression of 2-HG levels and subsequent activation of pro-oncogenic gene expression pathways.
Article
Oncology
Shi-Xun Lu, Yu-Hua Huang, Li-Li Liu, Chris Zhiyi Zhang, Xia Yang, Yuan-Zhong Yang, Chun-Kui Shao, Jian-Ming Li, Dan Xie, Xuchen Zhang, Dhanpat Jain, Jing-Ping Yun
Summary: The study demonstrates that AFP mRNA detected by RNAscope can increase the sensitivity in detecting HCC, and in combination with GPC3, can better differentiate HCC from benign/non-hepatocytic lesions.
BRITISH JOURNAL OF CANCER
(2021)
Article
Pathology
Deepika Kumar, Omeed Hafez, Dhanpat Jain, Xuchen Zhang
Summary: This study compared the histomorphologic features and phenotypic heterogeneity between primary and metastatic hepatocellular carcinoma (HCC) using 39 cases with both primary and metastatic tissues. The findings revealed significant intratumoral heterogeneity and histomorphologic discordance between primary and metastatic HCCs, with certain histologic patterns and subtypes being closely associated with metastasis. Further studies on a larger cohort are needed to better understand the mechanisms of HCC metastasis.
Article
Gastroenterology & Hepatology
Matthew J. McConnell, Nao Kawaguchi, Reiichiro Kondo, Aurelio Sonzogni, Lisa Licini, Clarissa Valle, Pietro A. Bonaffini, Sandro Sironi, Maria Grazia Alessio, Giulia Previtali, Michela Seghezzi, Xuchen Zhang, Alfred Lee, Alexander B. Pine, Hyung J. Chun, Xinbo Zhang, Carlos Fernandez-Hernando, Hua Qing, Andrew Wang, Christina Price, Zhaoli Sun, Teruo Utsumi, John Hwa, Mario Strazzabosco, Yasuko Iwakiri
Summary: Analysis of COVID-19 patients suggests that IL-6 trans-signaling may cause hepatic endotheliopathy and blood clot formation, leading to liver injury.
JOURNAL OF HEPATOLOGY
(2021)
Article
Pathology
David J. Papke Jr., Fei Dong, Xuchen Zhang, Rafal Kozielski, Olca Basturk, Christopher D. M. Fletcher, Lei Zhao
Summary: CNSET is a rare hepatic tumor affecting children and young adults, with varying sizes and CTNNB1 alterations. Clinical outcomes differ among patients, with some developing metastatic disease while others remain disease-free during follow-up.
Review
Gastroenterology & Hepatology
Timothy D. Murtha, Joshua Cornman-Homonoff, Rajasekhara Ayyagari, Xuchen Zhang, Ronald R. Salem
Summary: The incidence of pancreatic cystic neoplasms has increased, with serous cystadenoma traditionally considered benign but having a rare malignant variant called serous cystadenocarcinoma. Diagnosis of SCAC can be challenging due to its histological similarity with serous cystadenoma. In select patients, hepatic ablation may offer a less invasive but equally effective treatment option compared to hepatectomy.
Article
Pathology
Anisha Jain, Benjamin Mazer, Yanhong Deng, Maria Ciarleglio, Dhanpat Jain, Tamar Taddei, Xuchen Zhang
Summary: The study revealed that HCCs in noncirrhotic livers have larger tumor size, more macrotrabecular histologic pattern, higher grade and stage, higher rate of vascular invasion, and more anaplastic tumor cells compared to those in cirrhotic livers. Further research is needed to explore the oncogenesis pathways in noncirrhotic livers for better understanding of HCC pathogenesis.
AMERICAN JOURNAL OF CLINICAL PATHOLOGY
(2022)
Article
Medical Laboratory Technology
Pallavi A. Patil, Tamar Taddei, Dhanpat Jain, Xuchen Zhang
Summary: The study found that HNF-1 beta is a sensitive and specific marker for the diagnosis of iCCA and for distinguishing cHCC-CCA. It has higher diagnostic value compared to the previously identified marker, CRP.
ARCHIVES OF PATHOLOGY & LABORATORY MEDICINE
(2022)
Article
Gastroenterology & Hepatology
Reiichiro Kondo, Nao Kawaguchi, Matthew J. McConnell, Aurelio Sonzogni, Lisa Licini, Clarissa Valle, Pietro A. Bonaffini, Sandro Sironi, Maria Grazia Alessio, Giulia Previtali, Michela Seghezzi, Xuchen Zhang, Zhaoli Sun, Teruo Utsumi, Mario Strazzabosco, Yasuko Iwakiri
Summary: The study identified liver sinusoidal microthrombosis in COVID-19 patients, which was associated with higher serum ALT and AST levels. Platelet microthrombi were linked to increased ALT levels, while sinusoidal erythrocyte aggregation was not. Liver PMT was found to be an important thrombosis associated with liver injury in COVID-19.
HEPATOLOGY RESEARCH
(2021)
Article
Pathology
Bruce G. Rottmann, Natalie Patel, Muhammad Ahmed, Yanhong Deng, Maria Ciarleglio, Monika Vyas, Dhanpat Jain, Xuchen Zhang
Summary: This study investigates the prognostic significance of tumor-infiltrating neutrophil (TIN) in colorectal carcinomas (CRCs). The results show that high TIN is associated with higher histological grade, right-sided tumor location, advanced TNM stage, and higher rate of MMR-deficient CRCs. Patients with neutrophil-rich (NR) CRCs have significantly poorer 5-year recurrence-free survival compared to neutrophil-intermediate (NI) or neutrophil-poor (NP) CRCs. High TIN remains an independent risk factor for poor prognosis. NR CRCs are more commonly seen in MMR-deficient CRCs, and MMR-deficient NR CRCs have similar 5-year recurrence-free survival compared to MMR-proficient NR CRCs.
JOURNAL OF CLINICAL PATHOLOGY
(2023)
Article
Endocrinology & Metabolism
Parmanand Malvi, Radoslav Janostiak, Arvindhan Nagarajan, Xuchen Zhang, Narendra Wajapeyee
Summary: ASAH1 is overexpressed in melanoma cells and promotes tumor growth and metastasis by suppressing peroxisome biogenesis and inhibiting ROS production. Targeting ASAH1 can inhibit melanoma growth and enhance the effectiveness of BRAF kinase inhibitors.
MOLECULAR METABOLISM
(2021)
Article
Pathology
Tieying Hou, Zhaohai Yang, Qingzhao Zhang, Xuchen Zhang, Xiaoyan Liao, Jingmei Lin
Summary: Preoperative neoadjuvant therapy can lead to a histology shift from esophageal adenocarcinoma to neuroendocrine neoplasm in some cases. The underlying mechanism is uncertain and limited information is available. This shift might have implications for prognosis and treatment strategies.
INTERNATIONAL JOURNAL OF SURGICAL PATHOLOGY
(2023)
Article
Medicine, Research & Experimental
Kishu Ranjan, Matija Hedl, Saloni Sinha, Xuchen Zhang, Clara Abraham
Summary: The study reveals the crucial role of RNF186 in modulating PRR-initiated functions, promoting the unfolded protein response through ubiquitination of ATF6, and leading to downstream signaling, cytokine secretion, and antimicrobial pathway induction. Variant RNF186 alleles associated with IBD affect NOD2-induced outcomes, which can be restored by rescuing UPR signaling.
JOURNAL OF CLINICAL INVESTIGATION
(2021)