Article
Medicine, General & Internal
Christiane Palm, Catherine E. E. Connolly, Regina Masser, Barbara Padberg Sgier, Eva Karamitopoulou, Quentin Simon, Beata Bode, Marianne Tinguely
Summary: This study evaluated the use of a digital and AI-assisted workflow for determining HER2 status in breast cancer patients. The results showed that this method was in accordance with the ASCO/CAP guidelines and had high agreement between pathologists and AI.
Review
Oncology
Yanjun Hou, Hiroaki Nitta, Zaibo Li
Summary: HER2 intratumoral heterogeneity (ITH) is a common phenomenon in breast cancer, characterized by the coexistence of tumor cell subpopulations with different HER2 gene or protein expression. It has been associated with poor prognosis in patients receiving anti-HER2 targeted therapies and proposed as a potential mechanism for anti-HER2 resistance. HER2 ITH can be categorized into non-genetic and genetic ITH based on different HER2 genetic amplification, with genetic ITH exhibiting clustered, mosaic, and scattered distribution patterns. Digital image analysis has emerged as a promising method to accurately and objectively assess HER2 ITH.
Article
Oncology
Henrik Failmezger, Harald Hessel, Ansh Kapil, Guenter Schmidt, Nathalie Harder
Summary: Identifying new tumor biomarkers is crucial in cancer research. Our novel approaches for quantitatively scoring spatial marker expression heterogeneity outperform expression averages, showing the importance of considering spatial variability in tumor biology research.
FRONTIERS IN ONCOLOGY
(2022)
Article
Pathology
Jianghua Wu, Changling Liu, Xiaoqing Liu, Wei Sun, Linfeng Li, Nannan Gao, Yajun Zhang, Xin Yang, Junjie Zhang, Haiyue Wang, Xinying Liu, Xiaozheng Huang, Yanhui Zhang, Runfen Cheng, Kaiwen Chi, Luning Mao, Lixin Zhou, Dongmei Lin, Shaoping Ling
Summary: An AI system was developed for automated assessment of PD-L1 expression in non-small cell lung cancer, showing strong consistency with pathologists in tumor proportion score calculation. The system has the potential to improve diagnostic accuracy and efficiency by accurately evaluating the percentage of tumor cells expressing PD-L1.
Article
Pathology
Ana Leni Frei, Raphael Oberson, Elias Baumann, Aurel Perren, Rainer Grobholz, Alessandro Lugli, Heather Dawson, Christian Abbet, Ibai Lertxundi, Stefan Reinhard, Aart Mookhoek, Johann Feichtinger, Rossella Sarro, Gallus Gadient, Corina Dommann-Scherrer, Jessica Barizzi, Sabina Berezowska, Katharina Glatz, Susanne Dertinger, Yara Banz, Rene Schoenegg, Laura Rubbia-Brandt, Achim Fleischmann, Guenter Saile, Pierre Mainil-Varlet, Ruggero Biral, Luca Giudici, Alex Soltermann, Audrey Baur Chaubert, Sylvia Stadlmann, Joachim Diebold, Kristof Egervaril, Charles Beniere, Francesca Saro, Andrew Janowczyk, Inti Zlobec
Summary: Estimating tumor cell fraction (TCF) is a common clinical task with high variability among pathologists. This study evaluated the impact of using a tumor cell fraction computer-aided diagnostic (TCFCAD) tool to support pathologists' evaluation. The results showed that with the assistance of TCFCAD, interobserver variability decreased and estimates were closer to the ground truth. Pathologists also reported increased confidence in their assessments when aided by the TCFCAD tool.
Review
Cell Biology
Zaibo Li, David J. Dabbs
Summary: Immunohistochemistry plays a vital role in breast pathology by providing diagnostic and prognostic information. However, there are challenges in interpreting certain markers to differentiate different types of breast cancer.
Article
Pathology
Charles J. Robbins, Aileen I. Fernandez, Gang Han, Serena Wong, Malini Harigopal, Mirna Podoll, Kamaljeet Singh, Amy Ly, M. Gabriela Kuba, Hannah Wen, Mary Ann Sanders, Jane Brock, Shi Wei, Oluwole Fadare, Krisztina Hanley, Julie Jorns, Olivia L. Snir, Esther Yoon, Kim Rabe, T. Rinda Soong, Emily S. Reisenbichler, David L. Rimm
Summary: This study evaluated the concordance and interrater reliability of scoring HER2 IHC in breast cancer biopsies by 18 breast cancer-specialized pathologists. The results showed poor concordance within the intermediate categories and for the IHC 0 cases. The use of a 3-category system partially reduced the discordance. The study also revealed the optimal number of raters for determining HER2 IHC scores of 0 and 3+.
Article
Oncology
Lan Shu, Yiwei Tong, Zhuoxuan Li, Xiaosong Chen, Kunwei Shen
Summary: HER2 1+ cases of breast cancer are similar to HER2 0 cases in terms of clinicopathological features and mRNA expression, but different from HER2 2+/FISH- cases. There is poor concordance between IHC/FISH and qRT-PCR for HER2-negative tumors. The current definition of HER2-low expression with the lower boundary of HER2 IHC 1+ may be inaccurate.
Review
Biochemistry & Molecular Biology
Elham Sajjadi, Elena Guerini-Rocco, Elisa De Camilli, Oriana Pala, Giovanni Mazzarol, Konstantinos Venetis, Mariia Ivanova, Nicola Fusco
Summary: The introduction of novel anti-HER2 antibody-drug conjugates (ADC) has expanded the spectrum of HER2 status in breast cancer, challenging the identification of HER2-low tumors. Accurate and reproducible testing strategies are necessary to maximize therapeutic opportunities for HER2-low breast cancer patients. This article highlights the barriers and discusses practical solutions for improving HER2-low assessment.
FRONTIERS IN MOLECULAR BIOSCIENCES
(2023)
Article
Oncology
Yoshiya Horimoto, Yumiko Ishizuka, Yuko Ueki, Toru Higuchi, Atsushi Arakawa, Mitsue Saito
Summary: For HER2-positive tumors, there was no difference in disease-free survival between IHC(2+)/FISH(+) tumors and IHC(3+) tumors, but there was a difference in survival after developing metastasis.
Article
Pathology
Abeer M. Salama, Matthew G. Hanna, Dilip Giri, Brie Kezlarian, Marc-Henri Jean, Oscar Lin, Christina Vallejo, Edi Brogi, Marcia Edelweiss
Summary: The study evaluated the utility of digital review of breast cancer immunohistochemical markers using whole slide images from formalin fixed paraffin-embedded cytology cell block specimens. The results showed strong concordance between digital and microscopic reads, as well as between different scanners, indicating that digital images are reliable for assessment and offer reproducibility similar to microscope reads in breast cancer IHC.
Article
Chemistry, Multidisciplinary
Soo Jeong Nam, Yosep Chong, Chan Kwon Jung, Tae-Yeong Kwak, Ji Youl Lee, Jihwan Park, Mi Jung Rho, Heounjeong Go
Summary: The study found that Korean pathologists have a high level of awareness and positive attitude towards digital pathology, with the belief that CAD software can improve the diagnostic process. They also consider multidisciplinary care or conference accessibility, remote consultation, and big data building to be useful parts of digital pathology systems.
APPLIED SCIENCES-BASEL
(2021)
Article
Oncology
Joseph Kattan, Fady El Karak, Fadi Farhat, Dany Abi Gerges, Walid Mokaddem, Georges Chahine, Saad Khairallah, Najla Fakhruddin, Jawad Makarem, Fadi Nasr
Summary: This study reports on the prevalence of HER2-neu in newly diagnosed gastric cancer patients in Lebanon, as well as the correlation between IHC and ISH results. The study found a relatively high prevalence of HER2-neu over expression in these patients.
Article
Oncology
Fatma Nihan Akkoc Mustafayev, Mihir Amitabh Shukla, Amanda Lanier, Denai R. Milton, Angelica M. Gutierrez, Stephen K. Gruschkus, John E. Lewis, Rashmi K. Murthy, Banu K. Arun
Summary: BRCA1/2 mutations occurred in 6.6% of patients with human epidermal growth factor receptor 2 (HER2/neu)-positive breast cancer. However, BRCA mutation status did not affect survival outcomes in patients who had HER2/neu-positive breast cancer.
Review
Oncology
Erika Hamilton, Mythili Shastry, S. Michelle Shiller, Rongqin Ren
Summary: The heterogeneity of HER2 expression in breast cancer is being recognized as an important factor that impacts treatment outcomes, with the development of novel therapies to target tumors with non-uniform HER2 expression.
CANCER TREATMENT REVIEWS
(2021)
Article
Oncology
Louise Brinton, Jonine Figueroa, Ernest Adjei, Daniel Ansong, Richard Biritwum, Lawrence Edusei, Kofi M. Nyarko, Seth Wiafe, Joel Yarney, Beatrice Wiafe Addai, Baffour Awuah, Joe Nat Clegg-Lamptey
BREAST CANCER RESEARCH AND TREATMENT
(2017)
Article
Cell Biology
Joon-Yong Chung, Joon Seon Song, Kris Ylaya, John D. Sears, Lauren Choi, Hanbyoul Cho, Avi Z. Rosenberg, Stephen M. Hewitt
JOURNAL OF HISTOCHEMISTRY & CYTOCHEMISTRY
(2018)
Letter
Cell Biology
Stephen M. Hewitt
JOURNAL OF HISTOCHEMISTRY & CYTOCHEMISTRY
(2017)
Article
Transplantation
Laura H. Mariani, Sebastian Martini, Laura Barisoni, Pietro A. Canetta, Jonathan P. Troost, Jeffrey B. Hodgin, Matthew Palmer, Avi Z. Rosenberg, Kevin V. Lemley, Hui-Ping Chien, Jarcy Zee, Abigail Smith, Gerald B. Appel, Howard Trachtman, Stephen M. Hewitt, Matthias Kretzler, Serena M. Bagnasco
NEPHROLOGY DIALYSIS TRANSPLANTATION
(2018)
Review
Oncology
Maria Vittoria Dieci, Nina Radosevic-Robin, Susan Fineberg, Gert van den Eynden, Nils Ternes, Frederique Penault-Llorca, Giancarlo Pruneri, Timothy M. D'Alfonso, Sandra Demaria, Carlos Castaneda, Joselyn Sanchez, Sunil Badve, Stefan Michiels, Veerle Bossuyt, Federico Rojo, Baljit Singh, Torsten Nielsen, Giuseppe Viale, Seong-Rim Kim, Stephen Hewitt, Stephan Wienert, Sybille Loibl, David Rimm, Fraser Symmans, Carsten Denkert, Sylvia Adams, Sherene Loi, Roberto Salgado
SEMINARS IN CANCER BIOLOGY
(2018)
Editorial Material
Oncology
Stephen M. Hewitt
JNCI-JOURNAL OF THE NATIONAL CANCER INSTITUTE
(2020)
Article
Pathology
Jeong Won Kim, Joon-Yong Chung, Kris Ylaya, Yoonho Park, Sun-Young Jun, Seung-Mo Hong, Stephen M. Hewitt
Summary: The study revealed that high expression of SOX2 in patients with small intestinal adenocarcinomas is associated with shorter overall survival and has the potential to predict clinical outcomes.
Article
Medicine, Research & Experimental
Ilseon Hwang, Jeong Won Kim, Kris Ylaya, Eun Joo Chung, Haruhisa Kitano, Candice Perry, Jun Hanaoka, Junya Fukuoka, Joon-Yong Chung, Stephen M. Hewitt
JOURNAL OF TRANSLATIONAL MEDICINE
(2020)
Article
Multidisciplinary Sciences
Saumya Tiwari, Andre Kajdacsy-Balla, Joshua Whiteley, Georgina Cheng, Stephen M. Hewitt, Rohit Bhargava
Summary: This study introduces a measurement framework based on high-definition infrared imaging that uses the intrinsic chemical contrast of tissue to label unique components of tumors and their microenvironments, predicting overall survival in colon cancer patients. The results reveal the association between tumor spatial organization and disease progression.
Article
Medicine, Research & Experimental
Candace C. Liu, Marc Bosse, Alex Kong, Adam Kagel, Robert Kinders, Stephen M. Hewitt, Sushama Varma, Matt van de Rijn, Stanislaw H. Nowak, Sean C. Bendall, Michael Angelo
Summary: The study validated the use of MIBI-TOF for imaging proteins in human tissue and compared it to traditional immunohistochemistry methods. The results showed that MIBI-TOF can generate consistent and quantitative annotations of clinically relevant cell states and provide a scalable benchmark for multiplexed immunohistochemistry approaches.
LABORATORY INVESTIGATION
(2022)
Article
Medicine, Research & Experimental
Sandeep K. Singhal, Jung S. Byun, Tingfen Yan, Ryan Yancey, Ambar Caban, Sara Gil Hernandez, Sediqua Bufford, Stephen M. Hewitt, Joy Winfield, Jaya Pradhan, Vesco Mustkov, Jasmine A. McDonald, Eliseo J. Perez-Stable, Anna Maria Napoles, Nasreen Vohra, Adriana De Siervi, Clayton Yates, Melissa B. Davis, Mei Yang, Yien Che Tsai, Allan M. Weissman, Kevin Gardner
Summary: Women of African ancestry have higher rates of breast cancer mortality, and differences in tumor biology may play a role in these disparities. The protein gp78, found in patient breast cancer cells, is associated with poor survival outcomes in both ER+ and ER- tumors. Breast cancers with high levels of gp78 are enriched in gene expression pathways related to cell cycle, metabolism, signaling, and stress response. Gp78 protein is an independent predictor of poor outcomes in women of African ancestry, and gene expression signatures stratified by gp78 expression are strong predictors of recurrence and treatment response.
Article
Oncology
Sherry X. Yang, Stephen M. Hewitt, John Yu
Summary: The role of lymph node involvement and tumor size in metastatic disease, including breast cancer, is examined in this study. The findings suggest that nodal involvement and T stage are independent risk factors for mortality in patients with de novo metastatic breast cancer. The study also highlights the significance of positive lymph node count, tumor size, and chest wall involvement in breast cancer-specific mortality. These findings have important implications for the management and treatment of metastatic breast cancer patients.
NPJ PRECISION ONCOLOGY
(2022)
Article
Cell Biology
Kyungeun Kim, Kris Ylaya, Candice Perry, Mi-Yeon Lee, Jeong Won Kim, Joon-Yong Chung, Stephen M. Hewitt
Summary: Water is a crucial factor for protein and RNA degradation in stored tissue sections, and storage conditions can affect the expression of certain key proteins and RNA integrity in breast tissue.
BIOPRESERVATION AND BIOBANKING
(2023)
Article
Multidisciplinary Sciences
Lichun Ma, Sophia Heinrich, Limin Wang, Friederike L. Keggenhoff, Subreen Khatib, Marshonna Forgues, Michael Kelly, Stephen M. Hewitt, Areeba Saif, Jonathan M. Hernandez, Donna Mabry, Roman Kloeckner, Tim F. Greten, Jittiporn Chaisaingmongkol, Mathuros Ruchirawat, Jens U. Marquardt, Xin Wei Wang
Summary: Intratumor heterogeneity arises from the evolution of tumor cells and their interactions with the tumor microenvironment. This study uses single-cell RNA sequencing to analyze liver cancer patients, identifying cellular dynamics and communication networks between malignant cells and tumor-associated immune cells. The findings validate the stable molecular networks of malignant ecosystems and potentially open up new therapeutic opportunities.
NATURE COMMUNICATIONS
(2022)
Article
Medicine, Research & Experimental
Nathan Simon, Antonella Antignani, Stephen M. Hewitt, Massimo Gadina, Christine Alewine, David FitzGerald