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https://www.readbyqxmd.com/read/29683816/immunohistochemical-detection-and-molecular-characterization-of-idh-mutant-sinonasal-undifferentiated-carcinomas
#1
Jeffrey K Mito, Justin A Bishop, Peter M Sadow, Edward B Stelow, William C Faquin, Stacey E Mills, Jeffrey F Krane, Christopher A French, Christopher D M Fletcher, Jason L Hornick, Lynette M Sholl, Vickie Y Jo
Recent studies have identified recurrent isocitrate dehydrogenase 2 (IDH2) mutations in a subset of sinonasal undifferentiated carcinomas (SNUCs); however, the true frequency of IDH mutations in SNUC is unknown. We evaluated the utility of mutation-specific IDH1/2 immunohistochemistry (IHC) in a large multi-institutional cohort of SNUC and morphologic mimics. IHC using a multispecific antibody for IDH1/2 (R132/R172) mutant protein was performed on 193 sinonasal tumors including: 53 SNUCs, 8 poorly differentiated carcinomas (PDCARs) and 132 histologic mimics...
April 20, 2018: American Journal of Surgical Pathology
https://www.readbyqxmd.com/read/29608884/detection-of-mutations-in-barrett-s-esophagus-before-progression-to-high-grade-dysplasia-or-adenocarcinoma
#2
Matthew D Stachler, Nicholas D Camarda, Christopher Deitrick, Anthony Kim, Agoston T Agoston, Robert D Odze, Jason L Hornick, Anwesha Nag, Aaron R Thorner, Matthew Ducar, Amy Noffsinger, Richard H Lash, Mark Redston, Scott L Carter, Jon M Davison, Adam J Bass
BACKGROUND & AIMS: Barrett's esophagus (BE) is the greatest risk factor for esophageal adenocarcinoma, but only a small proportion of patients with BE develop cancer. Biomarkers might be able to identify patients at highest risk of progression. We investigated genomic differences in surveillance biopsies collected from patients whose BE subsequently progressed compared to patients whose disease did not progress. METHODS: We performed a retrospective case-control study of 24 patients with BE that progressed to high-grade dysplasia (HGD, n=14) or esophageal adenocarcinoma (EAC, n=10)...
March 30, 2018: Gastroenterology
https://www.readbyqxmd.com/read/29605270/pumpless-arteriovenous-extracorporeal-membrane-oxygenation-a-novel-mode-of-respiratory-support-in-a-lamb-model-of-congenital-diaphragmatic-hernia
#3
Emily A Partridge, Marcus G Davey, Matthew Hornick, Kevin C Dysart, Aliza Olive, Robert Caskey, James T Connelly, Holly L Hedrick, William H Peranteau, Alan W Flake
BACKGROUND: Extracorporeal membrane oxygenation (ECMO) is commonly required in neonates with congenital diaphragmatic hernia (CDH) complicated by pulmonary hypertension (PH). ECMO carries significant risk, and is contraindicated in the setting of extreme prematurity or intracranial hemorrhage. Pumpless arteriovenous ECMO (P-ECMO) may represent an alternative for respiratory support. The present study summarizes our initial experience with P-ECMO in a lamb model of CDH. STUDY DESIGN: Surgical creation of CDH was performed at 65-75days' gestation...
March 9, 2018: Journal of Pediatric Surgery
https://www.readbyqxmd.com/read/29420353/clusterin-in-neuroendocrine-epithelial-neoplasms-absence-of-expression-in-a-well-differentiated-tumor-suggests-a-jejunoileal-origin
#4
Thomas W Czeczok, Kristen M Stashek, Jessica E Maxwell, Thomas M O'Dorisio, James R Howe, Jason L Hornick, Andrew M Bellizzi
Clusterin, a widely expressed, tissue-specific glycoprotein, is a diagnostic marker of several tumor types, including anaplastic large cell lymphoma, follicular dendritic cell sarcoma, and tenosynovial giant cell tumor. A recent study has suggested it is highly expressed by well-differentiated neuroendocrine tumors (NET) arising at most anatomic sites, with the exception of jejunoileal tumors, and that it is similarly not expressed by poorly differentiated neuroendocrine carcinomas (NEC). We sought to validate this result in a large cohort of NETs and NECs...
February 2018: Applied Immunohistochemistry & Molecular Morphology: AIMM
https://www.readbyqxmd.com/read/29392729/umbilical-cannulation-optimizes-circuit-flows-in-premature-lambs-supported-by-the-extra-uterine-environment-for-neonatal-development-extend
#5
M A Hornick, M G Davey, E A Partridge, A Y Mejaddam, P E McGovern, A M Olive, G Hwang, J Kim, O Castillo, K Young, J Han, S Zhao, J T Connelly, K C Dysart, J Rychik, W H Peranteau, A W Flake
EXTEND (EXTra-uterine Environment for Neonatal Development) is a novel system that promotes physiologic development by maintaining the premature lamb in a sterile fluid environment and providing gas exchange via a pumpless arteriovenous oxygenator circuit. During the development of EXTEND, different cannulation strategies evolved with the aim to improve circuit flow. This study examines how different cannulation strategies affect EXTEND circuit hemodynamics in extreme premature lambs. 17 premature lambs were cannulated at gestational ages 105-117 days (term 145-150 days) and supported on EXTEND for up to 4 weeks...
February 1, 2018: Journal of Physiology
https://www.readbyqxmd.com/read/29385322/sox10-keratin-dual-color-immunohistochemistry-an-effective-first-line-test-for-the-workup-of-epithelioid-malignant-neoplasms-in-fna-and-small-biopsy-specimens
#6
Jeffrey K Mito, James R Conner, Jason L Hornick, Edmund S Cibas, Xiaohua Qian
BACKGROUND: The characterization of poorly differentiated neoplasms in fine-needle aspiration (FNA) and small biopsy specimens usually requires immunohistochemistry (IHC) with a panel of markers. Because of an increasing need to preserve limited diagnostic material for tumor genotyping and a mounting demand for cost containment, the authors investigated the usefulness of dual-color IHC with antibodies directed against broad-spectrum keratins and SOX10, a neuroectodermal transcription factor consistently expressed in melanoma, in the workup of epithelioid malignant neoplasms...
January 31, 2018: Cancer Cytopathology
https://www.readbyqxmd.com/read/29340997/immunohistochemical-biomarkers-of-mesenchymal-neoplasms-in-endocrine-organs-diagnostic-pitfalls-and-recent-discoveries
#7
Yin P Hung, Jason L Hornick
Mesenchymal neoplasms rarely present in or adjacent to endocrine organs. In this context, the recognition of these rare tumor types can be challenging, with significant potential for misdiagnosis as sarcomatoid carcinomas (i.e., anaplastic thyroid carcinoma and sarcomatoid adrenal cortical carcinoma) or neuroendocrine carcinomas, depending upon the dominant histologic patterns. In this review, we address potential pitfalls in diagnosing selected mesenchymal neoplasms arising within or near endocrine organs, including dedifferentiated liposarcoma, synovial sarcoma, angiosarcoma, PEComa, proximal-type epithelioid sarcoma, Ewing sarcoma, and neuroblastoma...
January 16, 2018: Endocrine Pathology
https://www.readbyqxmd.com/read/29339836/the-role-of-metabolic-enzymes-in-mesenchymal-tumors-and-tumor-syndromes-genetics-pathology-and-molecular-mechanisms
#8
REVIEW
Inga-Marie Schaefer, Jason L Hornick, Judith V M G Bovée
The discovery of mutations in genes encoding the metabolic enzymes isocitrate dehydrogenase (IDH), succinate dehydrogenase (SDH), and fumarate hydratase (FH) has expanded our understanding not only of altered metabolic pathways but also epigenetic dysregulation in cancer. IDH1/2 mutations occur in enchondromas and chondrosarcomas in patients with the non-hereditary enchondromatosis syndromes Ollier disease and Maffucci syndrome and in sporadic tumors. IDH1/2 mutations result in excess production of the oncometabolite (D)-2-hydroxyglutarate...
January 16, 2018: Laboratory Investigation; a Journal of Technical Methods and Pathology
https://www.readbyqxmd.com/read/29332233/pilot-study-of-serial-flt-and-fdg-pet-ct-imaging-to-monitor-response-to-neoadjuvant-chemoradiotherapy-of-esophageal-adenocarcinoma-correlation-with-histopathologic-response
#9
Victor H Gerbaudo, Joseph H Killoran, Chun K Kim, Jason L Hornick, Jonathan A Nowak, Peter C Enzinger, Harvey J Mamon
OBJECTIVE: The aim of this prospective pilot study was to investigate the potential of serial FLT-PET/CT compared to FDG-PET/CT to provide an early indication of esophageal cancer response to concurrent neoadjuvant chemoradiation therapy. METHODS: Five patients with biopsy-proven esophageal adenocarcinomas underwent neoadjuvant chemoradiation (Tx) prior to minimally invasive esophagectomy. The presence of residual tumor was classified histologically using the Mandard et al...
April 2018: Annals of Nuclear Medicine
https://www.readbyqxmd.com/read/29327718/epithelioid-fibrous-histiocytoma-molecular-characterization-of-alk-fusion-partners-in-23-cases
#10
Brendan C Dickson, David Swanson, George S Charames, Christopher Dm Fletcher, Jason L Hornick
Epithelioid fibrous histiocytoma is a rare and distinctive cutaneous neoplasm. Most cases harbor ALK rearrangement and show ALK overexpression, which distinguish this neoplasm from conventional cutaneous fibrous histiocytoma and variants. SQSTM1 and VCL have previously been shown to partner with ALK in one case each of epithelioid fibrous histiocytoma. The purpose of this study was to examine a large cohort of epithelioid fibrous histiocytomas by next-generation sequencing to characterize the nature and prevalence of ALK fusion partners...
January 12, 2018: Modern Pathology: An Official Journal of the United States and Canadian Academy of Pathology, Inc
https://www.readbyqxmd.com/read/29327713/expression-of-enhancer-of-zeste-homolog-2-ezh2-protein-in-histiocytic-and-dendritic-cell-neoplasms-with-evidence-for-p-erk1-2-related-but-not-myc-or-p-stat3-related-cell-signaling
#11
Xuejun Tian, Jie Xu, Christopher Fletcher, Jason L Hornick, David M Dorfman
EZH2 is an important enzymatic subunit of the epigenetic regulator polycomb repressive complex 2 (PRC2), which controls gene silencing through post-translational modification, and is overexpressed in various carcinomas and hematopoietic neoplasms. We found that the majority of cases of histiocytic and dendritic cell neoplasms, including histiocytic sarcoma, follicular dendritic cell sarcoma, Langerhans cell histiocytosis, and interdigitating dendritic cell sarcoma, show strong EZH2 expression by immunohistochemical staining, in contrast to benign histiocytic lesions and normal cellular counterparts, which did not show EZH2 expression, suggesting that this molecule may function as an oncogenic protein in these neoplasms...
January 12, 2018: Modern Pathology: An Official Journal of the United States and Canadian Academy of Pathology, Inc
https://www.readbyqxmd.com/read/29282312/nlrp12-mediates-adverse-neutrophil-recruitment-during-influenza-virus-infection
#12
Emma E Hornick, Balaji Banoth, Ann M Miller, Zeb R Zacharias, Nidhi Jain, Mary E Wilson, Katherine N Gibson-Corley, Kevin L Legge, Gail A Bishop, Fayyaz S Sutterwala, Suzanne L Cassel
Exaggerated inflammatory responses during influenza A virus (IAV) infection are typically associated with severe disease. Neutrophils are among the immune cells that can drive this excessive and detrimental inflammation. In moderation, however, neutrophils are necessary for optimal viral control. In this study, we explore the role of the nucleotide-binding domain leucine-rich repeat containing receptor family member Nlrp12 in modulating neutrophilic responses during lethal IAV infection. Nlrp12-/- mice are protected from lethality during IAV infection and show decreased vascular permeability, fewer pulmonary neutrophils, and a reduction in levels of neutrophil chemoattractant CXCL1 in their lungs compared with wild-type mice...
February 1, 2018: Journal of Immunology: Official Journal of the American Association of Immunologists
https://www.readbyqxmd.com/read/29220288/contemporary-sarcoma-diagnosis-genetics-and-genomics
#13
Inga-Marie Schaefer, Gregory M Cote, Jason L Hornick
Sarcomas include diverse mesenchymal neoplasms with widely varied prognosis, clinical behavior, and treatment. Owing to their rarity and histologic overlap, accurate diagnosis of sarcomas can be challenging. Our approach has evolved dramatically in the past few decades, where novel insights into the molecular pathogenetic basis for sarcomas has dramatically (re)shaped contemporary diagnosis, building on a largely morphology- and clinical presentation-based strategy. Examples include the introduction of novel immunohistochemical markers that serve as surrogates for molecular genetic alterations and identification of characteristic molecular alterations...
January 10, 2018: Journal of Clinical Oncology: Official Journal of the American Society of Clinical Oncology
https://www.readbyqxmd.com/read/29190760/simulated-ocean-acidification-reveals-winners-and-losers-in-coastal-phytoplankton
#14
Lennart T Bach, Santiago Alvarez-Fernandez, Thomas Hornick, Annegret Stuhr, Ulf Riebesell
The oceans absorb ~25% of the annual anthropogenic CO2 emissions. This causes a shift in the marine carbonate chemistry termed ocean acidification (OA). OA is expected to influence metabolic processes in phytoplankton species but it is unclear how the combination of individual physiological changes alters the structure of entire phytoplankton communities. To investigate this, we deployed ten pelagic mesocosms (volume ~50 m3) for 113 days at the west coast of Sweden and simulated OA (pCO2 = 760 μatm) in five of them while the other five served as controls (380 μatm)...
2017: PloS One
https://www.readbyqxmd.com/read/29180251/renal-cell-carcinoma-with-angioleiomyoma-like-stroma-and-clear-cell-papillary-renal-cell-carcinoma-exploring-sdhb-protein-immunohistochemistry-and-the-relationship-to-tuberous-sclerosis-complex
#15
Sean R Williamson, Jason L Hornick, John N Eble, Nilesh S Gupta, Craig G Rogers, Lawrence True, David J Grignon, Liang Cheng
Renal cell carcinoma (RCC) with angioleiomyoma-like stroma appears to be molecularly distinct from clear cell RCC; however, its relationship to clear cell papillary RCC remains debated. Recent studies have found that similar tumors sometimes occur in patients with tuberous sclerosis complex (TSC), of which one study found unexpectedly negative succinate dehydrogenase (SDH) B immunostaining. We evaluated immunohistochemistry for SDHB in 12 apparently sporadic RCCs with angioleiomyoma-like stroma and correlated with clinical information for stigmata of TSC...
November 24, 2017: Human Pathology
https://www.readbyqxmd.com/read/29156750/somatic-mutations-in-cdh1-and-ctnnb1-in-primary-carcinomas-at-13-anatomic-sites
#16
Evan L Busch, Jason L Hornick, Renato Umeton, Adem Albayrak, Neal I Lindeman, Laura E MacConaill, Elizabeth P Garcia, Matthew Ducar, Timothy R Rebbeck
Metastases are involved in most cancer deaths. Evidence has suggested that cancer cell detachment from primary tumors might occur largely via the mechanism of epithelial-mesenchymal transition (EMT) activated by epigenetic events, but data addressing other possible triggers of detachment, particularly genetic mutations, have been limited. Using the Profile study of cancer genomics at Dana-Farber Cancer Institute, we examined somatic mutations in the EMT genes CDH1 in 5,106 primary carcinomas and CTNNB1 in 7,578 primary carcinomas across 13 anatomic sites: urinary bladder, breast, colon/rectum, endometrium, esophagus, kidney, lung, ovary, pancreas, prostate, skin (non-melanoma), stomach, and thyroid...
October 17, 2017: Oncotarget
https://www.readbyqxmd.com/read/29131068/maternal-cannabinoid-use-alters-cannabinoid-cb1-and-endothelin-etb-receptor-expression-in-the-brains-of-dams-but-not-their-offspring
#17
Aarti Amlani, Mary G Hornick, Kevin Cooper, Preetha Prazad, Ramona Donovan, Anil Gulati
According to the 2015 National Survey on Drug Use and Health, cannabis (marijuana) is the most commonly used recreational drug in the US. Among pregnant women aged 14-55 years, 3.4% were cannabis users. Presently, little is known about the neurodevelopmental effect of cannabis use during pregnancy and/or nursing on neonates. Endothelin (ET) is essential for normal development of the central nervous system (CNS). Decreases in ETB receptor expression correlate with a decline in nerve growth factor (NGF) and an increase in vascular endothelial growth factor (VEGF) in postnatal brain...
November 4, 2017: Developmental Neuroscience
https://www.readbyqxmd.com/read/29106463/correspondence
#18
Isaac H Solomon, Jason L Hornick, Alvaro C Laga
No abstract text is available yet for this article.
November 2, 2017: American Journal of Clinical Pathology
https://www.readbyqxmd.com/read/29098284/association-of-alterations-in-main-driver-genes-with-outcomes-of-patients-with-resected-pancreatic-ductal-adenocarcinoma
#19
Zhi Rong Qian, Douglas A Rubinson, Jonathan A Nowak, Vicente Morales-Oyarvide, Richard F Dunne, Margaret M Kozak, Marisa W Welch, Lauren K Brais, Annacarolina Da Silva, Tingting Li, Wanwan Li, Atsuhiro Masuda, Juhong Yang, Yan Shi, Mancang Gu, Yohei Masugi, Justin Bui, Caitlin L Zellers, Chen Yuan, Ana Babic, Natalia Khalaf, Andrew Aguirre, Kimmie Ng, Rebecca A Miksad, Andrea J Bullock, Daniel T Chang, Jennifer F Tseng, Thomas E Clancy, David C Linehan, Jennifer J Findeis-Hosey, Leona A Doyle, Aaron R Thorner, Matthew Ducar, Bruce Wollison, Angelica Laing, William C Hahn, Matthew Meyerson, Charles S Fuchs, Shuji Ogino, Jason L Hornick, Aram F Hezel, Albert C Koong, Brian M Wolpin
Importance: Although patients with resected pancreatic adenocarcinoma are at high risk for disease recurrence, few biomarkers are available to inform patient outcomes. Objective: To evaluate the alterations of the 4 main driver genes in pancreatic adenocarcinoma and patient outcomes after cancer resection. Design, Setting, and Participants: This study analyzed protein expression and DNA alterations for the KRAS, CDKN2A, SMAD4, and TP53 genes by immunohistochemistry and next-generation sequencing in formalin-fixed, paraffin-embedded tumors in 356 patients with resected pancreatic adenocarcinoma who were treated at the Dana-Farber/Brigham and Women's Cancer Center (October 26, 2002, to May 21, 2012), University of Rochester Medical Center (March 1, 2006, to November 1, 2013), or Stanford Cancer Institute (September 26, 1995, to May 22, 2013)...
March 8, 2018: JAMA Oncology
https://www.readbyqxmd.com/read/29048279/weather-dependent-risk-for-legionnaires-disease-united-states
#20
Jacob E Simmering, Linnea A Polgreen, Douglas B Hornick, Daniel K Sewell, Philip M Polgreen
Using the Nationwide Inpatient Sample and US weather data, we estimated the probability of community-acquired pneumonia (CAP) being diagnosed as Legionnaires' disease (LD). LD risk increases when weather is warm and humid. With warm weather, we found a dose-response relationship between relative humidity and the odds for LD. When the mean temperature was 60°-80°F with high humidity (>80.0%), the odds for CAP being diagnosed with LD were 3.1 times higher than with lower levels of humidity (<50.0%). Thus, in some regions (e...
November 2017: Emerging Infectious Diseases
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