Review
Oncology
Emily Neil, Valerie Kouskoff
Summary: To understand and treat epithelioid haemangioendothelioma, it is important to study and compare experimental models. This article presents and compares the currently available model systems for studying this disease, discussing the advantages and disadvantages of each model.
Article
Cell Biology
Jordan H. Driskill, Yonggang Zheng, Bo-Kuan Wu, Li Wang, Jing Cai, Dinesh Rakheja, Michael Dellinger, Duojia Pan
Summary: Epithelioid hemangioendothelioma (EHE) is a vascular cancer driven by a unique gene fusion between TAZ and CAMTA1, and inhibition of this fusion leads to regression of vascular tumors. Activation of TAZ also induces EHE-like tumors, suggesting TAZ activation may underlie the pathological features of EHE. Targeting TAZ-CAMTA1 as a therapeutic approach may be effective for treating EHE.
GENES & DEVELOPMENT
(2021)
Review
Oncology
Caleb N. Seavey, Ajaybabu V. Pobbati, Brian P. Rubin
Summary: Epithelioid hemangioendothelioma (EHE) is a rare vascular cancer with a unique WWTR1(TAZ)-CAMTA1 gene fusion. Studying this disease can provide insights into how dysregulation of TAZ promotes tumorigenesis and these findings can be applied to other YAP/TAZ-dependent cancers.
Article
Pathology
Pedram Argani, Sara E. Wobker, John M. Gross, Andres Matoso, Christopher D. M. Fletcher, Cristina R. Antonescu
Summary: This article reports three unusual mesenchymal neoplasms harboring the ASPSCR1-TFE3 gene fusion, with a morphologic phenotype more closely resembling PEComa rather than alveolar soft part sarcoma. These cases highlight the relatedness and overlap among Xp11 translocation neoplasms.
AMERICAN JOURNAL OF SURGICAL PATHOLOGY
(2022)
Article
Pathology
Jennifer L. Vazzano, Ashley Patton, Gabriel Tinoco, O. Hans Iwenofu
Summary: Epithelioid hemangioendothelioma (EHE) is a rare vascular tumor with indolent biology, commonly characterized by WWTR1::CAMTA1 or YAP1::TFE3 gene fusion. Primary intranodal EHE is extremely rare, and we reported a rare case of intranodal EHE with morphologic mimicry of metastatic carcinoma.
INTERNATIONAL JOURNAL OF SURGICAL PATHOLOGY
(2022)
Article
Biology
Jason K. H. Lai, Pearlyn J. Y. Toh, Hamizah A. Cognart, Geetika Chouhan, Timothy E. Saunders
Summary: This study reveals that DNA damage induced by Yap1 and Wwtr1 mutations in zebrafish can lead to apoptosis of epidermal basal cells, and that cell size plays a critical role in this process.
Article
Cell Biology
Caleb N. Seavey, Ajaybabu Pobbati, Andrea Hallett, Shuang Ma, Jordan P. Reynolds, Ryan Kanai, John M. Lamar, Brian P. Rubin
Summary: The study introduced a conditional EHE mouse model controlled by endogenous transcriptional regulators targeting the Wwtr1-Camta1 gene fusion. It demonstrated the ability of TAZ-CAMTA1 to specifically drive EHE formation and validated the model for preclinical studies on TAZ dysregulation in cancer. This research provides new insights for understanding the role of TAZ dysregulation in cancer formation and testing therapies targeting TAZ-CAMTA1, TAZ, and YAP/TAZ signaling.
GENES & DEVELOPMENT
(2021)
Article
Cell Biology
So Jung Park, Rebecca A. Frake, David C. Rubinsztein
Summary: Impaired autophagosome formation and reduced flux through the macroautophagy/autophagy pathway occur outside the brain as part of normal aging. Our study found that SORBS3 gene expression is significantly increased in the brains of older mice and humans. SORBS3 negatively regulates autophagy in several cell lines and its depletion leads to increased autophagosome formation. The upregulation of YAP1-WWTR1/TAZ target genes, including myosin- and actin-related genes, contributes to this process. Moreover, we observed downregulation of these target genes in older mouse and human brains. These findings suggest that increased SORBS3 expression contributes to autophagic decline in normal brain aging.
Article
Medical Laboratory Technology
Melanie Bourgeau, Anthony Martinez, Kristin K. Deeb, Michelle D. Reid, Melinda Lewis, Kimberly S. Point du Jour, Jinping Lai, Qiuying Shi
Summary: Epithelioid hemangioendothelioma (EHE) is a rare vascular tumor with intermediate malignancy, often showing indolent behavior. While most cases exhibit the characteristic WWTR1-CAMTA1 gene fusion, a subtype with YAP1-TFE3 fusion and distinctive morphology has been recently described. This report presents a case of YAP1-TFE3 fusion-associated EHE diagnosed on liver mass fine-needle aspiration and core biopsy in an 18-year-old male with synchronous lung and liver involvement, discussing the differential diagnosis of EHE on cytology specimens.
DIAGNOSTIC CYTOPATHOLOGY
(2021)
Article
Oncology
Ning Liu, Yi Chen, Lei Yang, Qiancheng Shi, Yanwen Lu, Wenliang Ma, Xiaodong Han, Hongqian Guo, Dongmei Li, Weidong Gan
Summary: The study demonstrates that androgen and androgen receptor (AR) play a facilitating role in the progression of Xp11.2 tRCC and may serve as a novel therapeutic target for Xp11.2 tRCC.
CLINICAL AND TRANSLATIONAL MEDICINE
(2022)
Editorial Material
Cell Biology
Mariana Pavel, So Jung Park, Radu Tanasa, David C. Rubinsztein
Summary: The YAP1-WWTR1/TAZ transcription co-factors play a crucial role in cell growth and may be dysregulated in cancer. The study reveals that alpha-catenin levels act as a switch in determining the response of YAP1-WWTR1/TAZ signaling after autophagy perturbations, with a complex feedback loop between YAP1-WWTR1/TAZ and autophagy. The integration of experimental and theoretical data provides insights into cell-specific and time-dependent responses to autophagy manipulations, potentially relevant in various cancer contexts.
Article
Cell Biology
Carina A. Dehner, David Sadegh, Fouad Boulos, Nidia Messias, Wei-Lien Wang, Elizabeth G. Demicco, John S. A. Chrisinger
Summary: CCST-L is a rare lung tumor that expresses TFE3 and harbors YAP1::TFE3 fusions. Initial data suggested a benign process, but there have been reports of cases with distant metastases.
Article
Pathology
Anna Calio, Matteo Brunelli, Stefano Gobbo, Serena Pedron, Diego Segala, Pedram Argani, Guido Martignoni
Summary: The study found that STING is expressed in almost all PEC lesions of the kidney, providing new insights into the role of autophagy in these lesions. The expression of STING may be useful in distinguishing different tumor types and for diagnostic purposes.
Article
Oncology
Caleb N. Seavey, Andrea Hallett, Shuo Li, Kepeng Che, Ajaybabu Pobbati, Shuang Ma, Ashley Burtscher, Ryan Kanai, John M. Lamar, Brian P. Rubin
Summary: This study evaluated the effect of CDKN2A loss on EHE tumorigenesis. The loss of CDKN2A enhanced the invasiveness of EHE, leading to earlier tumor-related morbidity/mortality and increased tumor cell proliferation. Additionally, the study successfully established the first EHE cell lines, which replicated the transcriptional profile of EHE and generated EHE tumors in immunodeficient mice.
CLINICAL CANCER RESEARCH
(2023)
Review
Biochemistry & Molecular Biology
Audrey Simonaggio, Damien Ambrosetti, Virginie Verkarre, Marie Auvray, Stephane Oudard, Yann-Alexandre Vano
Summary: MiTF/TFE translocation renal cell carcinoma (tRCC) is a rare and aggressive subtype of RCC, which is more prevalent in the pediatric population and represents 4% of all RCCs in adults. The diagnosis of tRCC involves translocations of genes such as TFE3, TFEB or MITF. TFE break-apart fluorescent in situ hybridization (FISH) is considered the gold standard for diagnosis. tRCC exhibits heterogeneous clinical behaviors and is more aggressive in adults. Effective treatment options for metastatic tRCC are limited, highlighting the need for better therapeutic approaches. Comprehensive genetic sequencing analyses have provided insights into the biological heterogeneity of tRCC, aiding in the development of more effective treatments.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2022)
Review
Oncology
Emily Z. Keung, Kate J. Krause, Jessica Maxwell, Carol D. Morris, Aimee M. Crago, Matthew T. Houdek, John Kane, Valerae Lewis, Dario Callegaro, Benjamin Miller, Alexander J. Lazar, Rebecca Gladdy, Chandrajit P. Raut, Nicola Fabbri, Waddah Al-Refaie, Mark Fairweather, Sandra L. Wong, Christina L. Roland
Summary: Regional lymph node metastasis (RLNM) is uncommon in patients with soft tissue sarcoma (STS), although certain STS subtypes are more prone to RLNM. The impact of node-positive disease on patient survival is still controversial. There is ongoing debate about the benefits of sentinel lymph node biopsy (SLNB) in STS patients. Further multicenter prospective studies are needed to determine the true incidence and potential benefits of SLNB in patients with clinically occult RLNM.
ANNALS OF SURGICAL ONCOLOGY
(2023)
Editorial Material
Oncology
Raymond S. Traweek, Allison N. Martin, Nikita F. Rajkot, B. Ashleigh Guadagnolo, Andrew J. Bishop, Alexander J. Lazar, Emily Z. Keung, Keila E. Torres, Kelly K. Hunt, Barry W. Feig, Christina L. Roland, Christopher P. Scally
ANNALS OF SURGICAL ONCOLOGY
(2023)
Article
Oncology
Raymond S. Traweek, Allison N. Martin, Nikita F. Rajkot, B. Ashleigh Guadagnolo, Andrew J. Bishop, Alexander J. Lazar, Emily Z. Keung, Keila E. Torres, Kelly K. Hunt, Barry W. Feig, Christina L. Roland, Christopher P. Scally
Summary: This study aimed to evaluate the short-term outcomes and morbidity after re-resection of unplanned excision of trunk and extremity soft tissue sarcoma (STS) to better understand the risks and benefits of this treatment strategy. The results showed that the rate of wound complications after re-resection was 45%, and radiation therapy and plastic surgery involvement were independently associated with wound complications. Additionally, 67% of patients had no evidence of residual disease in the re-resection specimen. Therefore, treatment plans and discussions with patients should include information about the expected pathological findings and morbidity of surgery.
ANNALS OF SURGICAL ONCOLOGY
(2023)
Editorial Material
Oncology
Emily Z. Keung, Kate J. Krause, Jessica Maxwell, Carol D. Morris, Aimee M. Crago, Matthew T. Houdek, John Kane, Valerae Lewis, Dario Callegaro, Benjamin Miller, Alexander J. Lazar, Rebecca Gladdy, Chandrajit P. Raut, Nicola Fabbri, Waddah Al-Refaie, Mark Fairweather, Sandra L. Wong, Christina L. Roland
ANNALS OF SURGICAL ONCOLOGY
(2023)
Article
Oncology
Yize Li, Tung-Shing M. Lih, Saravana M. Dhanasekaran, Rahul Mannan, Lijun Chen, Marcin Cieslik, Yige Wu, Rita Jiu-Hsien Lu, David J. Clark, Iga Koodziejczak, Runyu Hong, Siqi Chen, Yanyan Zhao, Seema Chugh, Wagma Caravan, Nataly Naser Al Deen, Noshad Hosseini, Chelsea J. Newton, Karsten Krug, Yuanwei Xu, Kyung-Cho Cho, Yingwei Hu, Yuping Zhang, Chandan Kumar-Sinha, Weiping Ma, Anna Calinawan, Matthew A. Wyczalkowski, Michael C. Wendl, Yuefan Wang, Shenghao Guo, Cissy Zhang, Anne Le, Aniket Dagar, Alex Hopkins, Hanbyul Cho, Felipe da Veiga Leprevost, Xiaojun Jing, Guo Ci Teo, Wenke Liu, Melissa A. Reimers, Russell Pachynski, Alexander J. Lazar, Arul M. Chinnaiyan, Brian A. Van Tine, Bing Zhang, Karin D. Rodland, Gad Getz, D. R. Mani, Pei Wang, Feng Chen, Galen Hostetter, Mathangi Thiagarajan, W. Marston Linehan, David Fenyo, Scott D. Jewell, Gilbert S. Omenn, Rohit Mehra, Maciej Wiznerowicz, Ana I. Robles, Mehdi Mesri, Tara Hiltke, Eunkyung An, Henry Rodriguez, Daniel W. Chan, Christopher J. Ricketts, Alexey I. Nesvizhskii, Hui Zhang, Li Ding
Summary: By integrating histopathologic, proteogenomic, and metabolomic analyses, this study reveals the inter- and intratumoral heterogeneity of clear cell renal cell carcinomas (ccRCCs). It identifies high-risk disease subsets based on tumor grade, BAP1 mutation, genome instability, hypermethylation, and protein glycosylation signature. RNA sequencing provides insights into gene signatures and potential targeted therapies, while in vitro cell line studies validate the efficacy of inhibiting identified phosphoproteome targets.
Article
Oncology
Tuyen Duong Thanh Nguyen, Yan Wang, Tuyen N. Bui, Rossana Lazcano, Davis R. Ingram, Min Yi, Varshini Vakulabharanam, Linjie Luo, Marc A. Pina, Cansu Karakas, Mi Li, Nicole M. Kettner, Neeta Somaiah, Peter J. Hougton, Osama Mawlawi, Alexander J. Lazar, Kelly K. Hunt, Khandan Keyomarsi
Summary: Treatment strategies with CDK4/6 inhibitors followed by DNA-damaging agents showed synergistic killing of Rb-positive sarcomas and can be noninvasively monitored using functional imaging and serum biomarkers. This approach provides a potential avenue for novel targeted therapies in sarcomas with intact Rb signaling.
Article
Cell Biology
Jacqueline E. Birkness-Gartman, Sintawat Wangsiricharoen, Alexander J. Lazar, John M. Gross
Summary: This study describes the clinicopathologic features of three oesophageal glomus tumours diagnosed at two large academic institutions between 1984 and 2022. These tumours exhibited aggressive behavior with metastases to multiple sites. Management by a multidisciplinary sarcoma team is recommended for optimal outcome.
Article
Oncology
Gabriele Romano, Francesca Paradiso, Peng Li, Pooja Shukla, Lindsay N. Barger, Olivia El Naggar, John P. Miller, Roger J. Liang, Timothy L. Helms, Alexander J. Lazar, Jennifer A. Wargo, Francesca Taraballi, James C. Costello, Lawrence N. Kwong
Summary: Patients with BRAF-mutant melanoma respond well to combined BRAF and MEK inhibition, but relapse is common within 2 years. Minimal residual disease (MRD), which consists of drug-tolerant tumor cells in a dormant state, is a major cause of drug resistance. By studying a mouse model, researchers found that sustaining chemokine signaling can impair MRD maintenance by increasing the recruitment of effector T cells.
CANCER IMMUNOLOGY RESEARCH
(2023)
Review
Oncology
Brandon M. Cope, Raymond S. Traweek, Rossana Lazcano, Emily Z. Keung, Alexander J. Lazar, Christina L. Roland, Elise F. Nassif
Summary: Immunotherapy has greatly improved cancer care, but leiomyosarcoma is not responsive to early immune-based therapies. This review discusses the results of immunotherapy trials in leiomyosarcoma and highlights the differences between soft-tissue and uterine leiomyosarcomas. It also explores the molecular subgroups of leiomyosarcomas and their impact on response to immune checkpoint blockade, proposing future directions for improving immunotherapy in leiomyosarcoma patients. Leiomyosarcoma is a rare and aggressive tumor with low tumor mutational burden, frequent alterations in certain genes, and a highly infiltrated immune microenvironment. This review provides insights for the development of biomarker-based immune therapies.
Article
Dermatology
Woo Cheal Cho, Wen Li, Jun Gu, Wei-Lien Wang, Jing Ning, Steven Sfamenos, Pavandeep Gill, Priyadharsini Nagarajan, Jonathan L. Curry, Alexander J. Lazar, Victor G. Prieto, Carlos A. Torres-Cabala, Phyu P. Aung
Summary: The clinical utility of TERT IHC to predict TGA status in AMs appears to be limited given its low specificity and positive predictive value.
JOURNAL OF CUTANEOUS PATHOLOGY
(2023)
Meeting Abstract
Oncology
Danh D. Truong, Salah-Eddine Lamhamedi-Cherradi, Mayinuer Maitituoheti, Hannah C. Beird, Chia-Chin Wu, Sandhya Krishnan, Davis Ingram, P. Andrew Futreal, Mark Titus, Alexander Lazar, Kunal Rai, A. Robert MacLeod, Najat C. Daw, Andrea Hayes, Joseph Ludwig
Meeting Abstract
Medicine, Research & Experimental
Rossana Lazcano, Davis Ingram, Alexander Lazar, Wei-Lien (Billy) Wang, Jeffrey Cloutier
LABORATORY INVESTIGATION
(2023)
Meeting Abstract
Medicine, Research & Experimental
Rossana Lazcano, Raymond Traweek, Davis Ingram, Khalida Wani, B. Ashleigh Guadagnolo, Ahsan Farooqi, Christina Roland, Emily Keung, Andrew Bishop, Wei-Lien (Billy) Wang, Elise Nassif, Alexander Lazar
LABORATORY INVESTIGATION
(2023)
Meeting Abstract
Medicine, Research & Experimental
Sintawat Wangsiricharoen, Davis Ingram, Alexander Lazar, Wei-Lien (Billy) Wang
LABORATORY INVESTIGATION
(2023)
Article
Oncology
Andres F. Espinoza, Kalyani R. Patel, Priya B. Shetty, Richard S. Whitlock, Pavel Sumazin, Xinjian Yu, Stephen F. Sarabia, Martin Urbicain, Andras Heczey, Prakash Masand, Sarah E. Woodfield, Dolores H. Lopez-Terrada, Sanjeev A. Vasudevan
Summary: This study indicates that PRETEXT IV staging is an independent predictor of relapsed hepatoblastoma. A combination of surgical and medical therapy for relapsed disease significantly improves survival outcomes.
