Biomarker p-120 Catenin Distinguishes Conventional Urothelial Carcinoma from Variants
|
By LabMedica International staff writers Posted on 24 Aug 2021 |
|
Image: Histopathology of (a) Usual-type high-grade urothelial carcinoma and (b) Positive E-cadherin expression in usual-type high-grade urothelial carcinoma. (Photo courtesy of Emory University School of Medicine)
Plasmacytoid urothelial carcinoma (PC-UC) is an infrequent and clinically aggressive variant of urothelial carcinoma (UC). Initially, PC-UC was identified based on morphology as a potential mimicker of malignant plasma cell and lymphoid neoplasms and is characterized by loss of E-cadherin (E-Cad)–mediated intercellular adhesion.
Sarcomatoid UC, is another rare and aggressive variant of UC that includes carcinomatous and sarcomatous components (i.e., dedifferentiated carcinoma). The latter can be represented by a nondescript high-grade spindle cell proliferation and/or it can demonstrate more lineage-specific change, including, but not limited to, leiomyosarcomatous, rhabdomyosarcomatous, and chondrosarcomatous differentiation.
Pathologists at the Brigham and Women's Hospital (Boston, MA, USA) included in a study included a total of 58 samples from 55 patients, as three cases had areas of both PC-UC and SUC. The final breakdown included 25 conventional invasive UCs, 22 PC-UCs, six SUCs, and five micropapillary UCs. Specimen types included 45 transurethral resections/bladder biopsies, three cystoprostatectomies, one anterior pelvic exenteration, one abdominoperineal resection, two biopsies of tumor from metastatic sites (one pelvic soft tissue nodule and one peritoneal nodule), one nephroureterectomy, one penectomy, and one autopsy case.
The team performed immunohistochemistry with the Envision Plus/horseradish peroxidase system (Dako Agilent, Carpinteria, CA, USA), a polyclonal antibody to p-120 (BD Biosciences, San Jose, CA, USA), and monoclonal antibodies against E-Cad (Dako Agilent,) and B-Cat (BD Biosciences). Following Tris-buffered saline rinses, the tissues were incubated with the Envision Plus or Novolink Polymer Detection system (Leica Biosystems, Buffalo Grove, IL, USA). Eight PC-UC cases had molecular characterization via the OncoPanel assay developed at the institution.
The scientists reported that E-cadherin, B-Cat, and p-120 showed membranous staining in all conventional and micropapillary UCs. In contrast, most PC-UCs were negative for E-Cad (17/22; 77%) with an additional 2/22 cases (9%) showing cytoplasmic with partial membranous staining. p-120 catenin demonstrated cytoplasmic or negative staining in 21/22 cases (95%). Most SUCs showed an absence of E-Cad (5/6; 83%) and cytoplasmic or negative p-120 in 5/6 cases (83%). Staining for B-Cat was also abnormal in a subset of PC-UCs and SUCs. Five PC-UC cases that harbored CDH1 gene variants were p-120 cytoplasmic positive.
The authors concluded that p-120 catenin is a useful adjunct biomarker to E-Cad in the clinically important distinction of PC-UC and SUC from conventional UC. In particular, the combination of cytoplasmic p-120 and loss of E-Cad is strongly supportive of PC-UC and SUC. The study was published on August 21, 2021 in the journal Archives of Pathology and Laboratory Medicine.
Related Links:
Brigham and Women's Hospital
Dako Agilent
BD Biosciences
Leica Biosystems
Sarcomatoid UC, is another rare and aggressive variant of UC that includes carcinomatous and sarcomatous components (i.e., dedifferentiated carcinoma). The latter can be represented by a nondescript high-grade spindle cell proliferation and/or it can demonstrate more lineage-specific change, including, but not limited to, leiomyosarcomatous, rhabdomyosarcomatous, and chondrosarcomatous differentiation.
Pathologists at the Brigham and Women's Hospital (Boston, MA, USA) included in a study included a total of 58 samples from 55 patients, as three cases had areas of both PC-UC and SUC. The final breakdown included 25 conventional invasive UCs, 22 PC-UCs, six SUCs, and five micropapillary UCs. Specimen types included 45 transurethral resections/bladder biopsies, three cystoprostatectomies, one anterior pelvic exenteration, one abdominoperineal resection, two biopsies of tumor from metastatic sites (one pelvic soft tissue nodule and one peritoneal nodule), one nephroureterectomy, one penectomy, and one autopsy case.
The team performed immunohistochemistry with the Envision Plus/horseradish peroxidase system (Dako Agilent, Carpinteria, CA, USA), a polyclonal antibody to p-120 (BD Biosciences, San Jose, CA, USA), and monoclonal antibodies against E-Cad (Dako Agilent,) and B-Cat (BD Biosciences). Following Tris-buffered saline rinses, the tissues were incubated with the Envision Plus or Novolink Polymer Detection system (Leica Biosystems, Buffalo Grove, IL, USA). Eight PC-UC cases had molecular characterization via the OncoPanel assay developed at the institution.
The scientists reported that E-cadherin, B-Cat, and p-120 showed membranous staining in all conventional and micropapillary UCs. In contrast, most PC-UCs were negative for E-Cad (17/22; 77%) with an additional 2/22 cases (9%) showing cytoplasmic with partial membranous staining. p-120 catenin demonstrated cytoplasmic or negative staining in 21/22 cases (95%). Most SUCs showed an absence of E-Cad (5/6; 83%) and cytoplasmic or negative p-120 in 5/6 cases (83%). Staining for B-Cat was also abnormal in a subset of PC-UCs and SUCs. Five PC-UC cases that harbored CDH1 gene variants were p-120 cytoplasmic positive.
The authors concluded that p-120 catenin is a useful adjunct biomarker to E-Cad in the clinically important distinction of PC-UC and SUC from conventional UC. In particular, the combination of cytoplasmic p-120 and loss of E-Cad is strongly supportive of PC-UC and SUC. The study was published on August 21, 2021 in the journal Archives of Pathology and Laboratory Medicine.
Related Links:
Brigham and Women's Hospital
Dako Agilent
BD Biosciences
Leica Biosystems
Gold Member
Flocked Fiber Swabs
Puritan® Patented HydraFlock®
Creatinine/eGFR Meter
StatSensor® Creatinine/eGFR Meter
Urine Analyzer
respons® UDS100
Latest Pathology News
- FDA-Cleared Digital Pathology Platform Expands Interoperability for Primary Diagnosis
- AI Pathology Tool Predicts Relapse Risk in Stage II Colorectal Cancer
- AI Pathology Tool Stratifies Rectal Cancer to Guide Chemoradiotherapy
- PD-L1 Assay Guides Pembrolizumab Eligibility in Ovarian, Fallopian Tube, and Peritoneal Cancers
- AI Digital Pathology Platform Standardizes IHC Scoring in Breast Cancer
- AI Bone Marrow Mapping Provides New Tool to Track Blood Cancer Severity
- Digital Pathology Tool Predicts Breast Cancer Outcomes and Therapy Response
- AI Tissue Imaging Helps Guide Targeted Therapy for Lung Cancer
- Imaging Platform Maps Lipid Accumulations in Fabry Heart Tissue
- Tissue-Based Gene Signature Signals Colorectal Cancer Recurrence Risk
- FDA-Approved Companion Diagnostic Detects PTEN Loss in Prostate Cancer
- New AI Test Delivers Rapid Breast Cancer Recurrence Predictions
- EBV Status Helps Predict Survival in Primary CNS Lymphoma
- AI Pathology Tool Predicts Immunotherapy Response in Rare Cancers
- Uncertainty-Aware AI Tool Improves Digital Pathology for Cancer Subtyping
- Study Highlights Biomarker Testing Delays in Lung Cancer Care
Channels
Clinical Chemistry
view channel
Blood Test on a Chip Offers Low-Cost Lung Cancer Detection Without DNA Sequencing
Lung cancer is the leading cause of cancer deaths worldwide, and screening often yields indeterminate results that prompt invasive workups. Computed tomography (CT) detects small nodules but can flag benign... Read more
Portable Troponin Assay Brings Heart Attack Diagnosis Closer to Patients
Timely confirmation of myocardial infarction often depends on laboratory testing that may not be immediately available at the point of care. This gap between clinical suspicion and definitive evidence... Read more
Molecular Diagnostics
view channel
Whole-Cell Genomic Analysis Expands the Potential of Liquid Biopsy
Liquid biopsy has expanded access to tumor genomics, but most blood-based assays rely on short, degraded fragments of cell-free circulating tumor DNA (ctDNA). Isolating intact circulating tumor cells from... Read more
Blood Test Could Help Fast-Track Lymphoma Diagnosis in Resource-Limited Settings
Lymphoma can be difficult to distinguish from infections and benign conditions, while definitive diagnosis often depends on surgical tissue sampling and specialized pathology that may not be readily available.... Read more
Hematology
view channel
New Genetic Findings Reveal Cause of Bone Marrow Failure Syndrome
Inherited bone marrow failure syndromes (IBMFS) impair the bone marrow’s ability to produce sufficient healthy blood cells and are associated with an increased risk of early-onset myelodysplastic syndromes (MDS).... Read more
Ultra-Portable Device Enables Finger-Prick Blood Testing at Home
Patients who need frequent blood tests often face repeated clinic visits that burden services and disrupt care. In the UK, millions of tests are performed each year to diagnose disease, guide therapy,... Read more
Immunology
view channel
Study Reveals Viral Protein Driving COVID-19-Related Vascular Injury
Lingering symptoms after acute COVID-19 infection remain a clinical challenge, with many patients experiencing fatigue, cognitive problems, and cardiovascular complications months later.... Read more
Study Reveals Immune Mechanism Driving Severe COVID-19 Progression
Severe COVID-19 has highlighted gaps in understanding of early antiviral responses, particularly why some patients deteriorate despite timely care. Type I interferons are central to host defense, yet their... Read more
Antibody Profiling Identifies Preclinical Inflammatory Bowel Disease Years Before Diagnosis
Inflammatory bowel disease often develops after a prolonged symptom-free period, complicating timely recognition and clinical intervention. Limited understanding of immune activity during this silent phase... Read more
Microbiology
view channel
Precision Screening Helps Close Hepatitis C Diagnosis and Treatment Gaps
Hepatitis C remains a leading cause of cirrhosis and liver cancer, yet many infections go undiagnosed or untreated because health systems fail to reach those at greatest risk. Although highly effective... Read more
Proteomic Workflow Maps Microbial and Host Responses in Intestinal Inflammation
The intestinal microbiome influences digestion, metabolism, and immunity, yet its complexity makes functional measurements difficult to obtain. DNA surveys can indicate which organisms and potential pathways... Read more
Metagenomic Sequencing Enables Faster Diagnosis of Respiratory Infections in Cystic Fibrosis
Serious lung infections remain a major cause of morbidity among people with cystic fibrosis, a life-threatening genetic disorder characterized by persistent airway colonization and frequent antimicrobial exposure.... Read more
Technology
view channel
Interoperable Data Platform Standardizes Multi-Cancer Blood Test Results
Proteotype Diagnostics has introduced Alchemi, a proprietary data and clinical workflow platform being developed for Enlighten, the company’s investigational blood-based multi-cancer test.... Read more
Training Device Improves Accuracy of Pooled Molecular Diagnostics
High-throughput molecular diagnostics have transformed infectious disease detection, but many workflows remain difficult to execute accurately without extensive training. Sample pooling can cut per‑test... Read more
New CE-Certified Software Advances Whole-Genome Cancer Testing
European hospitals are increasingly using comprehensive tumor genomics to guide therapy, but routine whole genome sequencing (WGS) requires validated, regulation-compliant workflows. A newly CE-certified... Read more
National Rare Disease Registry Standardizes Genetic and Clinical Data for Coordinated Care
Rare diseases collectively impose a significant clinical burden despite their individual rarity, often involving multisystem presentations and prolonged diagnostic journeys. Limited specialist expertise... Read moreIndustry
view channel
Standardized Staining Technology Advances Digital Pathology Workflows
Digital pathology is increasingly used to streamline cancer diagnostics, yet staining variability can hinder slide interpretation and limit the reliability of artificial intelligence tools.... Read more
Global Testing Service Advances Leukemia MRD Monitoring
KMT2A rearrangements drive aggressive subsets of acute myeloid leukemia (AML) and acute lymphoblastic leukemia (ALL) and are associated with relapse and poor outcomes. As menin inhibitors enter clinical... Read more
