ArticleModern pathology : an official journal of the United States and Canadian Academy of Pathology, Inc2020
Three-dimensional visualization of cleared human pancreas cancer reveals that sustained epithelial-to-mesenchymal transition is not required for venous invasion.
Article in Modern pathology : an official journal of the United States and Canadian Academy of Pathology, Inc, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 41 papers.
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Who cites it
41 citing papers in PubMed, 60 citations in OpenAlex.
- THBS2/CA19-9 Detecting Pancreatic Ductal Adenocarcinoma at Diagnosis Underperforms in Prediagnostic Detection: Implications for Biomarker Advancement.Cancer prevention research (Philadelphia, Pa.) · 2021Trial
- S100A4 promotes collective invasion of pancreatic ductal adenocarcinoma and its blockade suppresses metastasis.Cell communication and signaling : CCS · 2026Article
- Spotlight on challenges and novel methods in highly multiplexed tissue imaging-based spatial proteomics.Journal of translational medicine · 2026Review
- Three-dimensional reconstruction of gigapixel whole-mount histopathology specimens with RAPID.Scientific reports · 2026Article
- Mechanisms Underlying the Initiation and Termination of Collective Cell Migration: Perspectives for Understanding Development and Cancer Metastasis.BioEssays : news and reviews in molecular, cellular and developmental biology · 2026Review
- [Virtual histopathology of the pancreas: 3D insights using synchrotron-based imaging].Pathologie (Heidelberg, Germany) · 2026Article
- Histologic patterns of venous invasion in distal extrahepatic bile duct carcinoma correlate with prognosis.Virchows Archiv : an international journal of pathology · 2026Article
- Collective migration modes in development, tissue repair and cancer.Nature reviews. Molecular cell biology · 2025Review
- An injury-associated lobular microniche is associated with the classical tumor cell phenotype in pancreatic cancer.Nature communications · 2025Article
- Spatial profiling of human pancreatic ductal adenocarcinoma reveals molecular alterations associated with venous invasion.Science translational medicine · 2025Article
- Three-dimensional assessments are necessary to determine the true, spatially resolved composition of tissues.Cell reports methods · 2025Article
- Tissue inhibitor of metalloproteinase 1 as a biomarker of venous invasion in pancreatic ductal adenocarcinoma.American journal of cancer research · 2025Article
- Defining and modeling dynamic spatial heterogeneity within tumor microenvironments.Current opinion in cell biology · 2024Review
- Article
- Three-dimensional analysis of ductular reactions and their correlation with liver regeneration and fibrosis.Virchows Archiv : an international journal of pathology · 2024Article
- Efficient 3D imaging and pathological analysis of the human lymphoma tumor microenvironment using light-sheet immunofluorescence microscopy.Theranostics · 2024Article
- Engineering the future of 3D pathology.The journal of pathology. Clinical research · 2024Article
- Modelling 3D Tumour Microenvironment In Vivo: A Tool to Predict Cancer Fate.Current issues in molecular biology · 2023Article
- Infrared spectroscopic laser scanning confocal microscopy for whole-slide chemical imaging.Nature communications · 2023Article
- Three-dimensional analysis of human pancreatic cancer specimens by phase-contrast based X-ray tomography - the next dimension of diagnosis.Cancer imaging : the official publication of the International Cancer Imaging Society · 2023Article
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Authors and funding
15 authors at 3 institutions in 3 countries.
Funding
Abstract
Venous invasion is three times more common in pancreatic cancer than it is in other major cancers of the gastrointestinal tract, and venous invasion may explain why pancreatic cancer is so deadly. To characterize the patterns of venous invasion in pancreatic cancer, 52 thick slabs (up to 5 mm) of tissue were harvested from 52 surgically resected human ductal adenocarcinomas, cleared with a modified iDISCO method, and labeled with fluorescent-conjugated antibodies to cytokeratin 19, desmin, CD31, p53 and/or e-cadherin. Labeled three-dimensional (3D) pancreas cancer tissues were visualized with confocal laser scanning or light sheet microscopy. Multiple foci of venous and even arterial invasion were visualized. Venous invasion was detected more often in 3D (88%, 30/34 cases) than in conventional 2D slide evaluation (75%, 25/34 cases, P < 0.001). 3D visualization revealed pancreatic cancer cells crossing the walls of veins at multiple points, often at points where preexisting capillary structures bridge the blood vessels. The neoplastic cells often retained a ductal morphology (cohesive cells forming tubes) as they progressed from a stromal to intravenous location. Although immunolabeling with antibodies to e-cadherin revealed focal loss of expression at the leading edges of the cancers, the neoplastic cells within veins expressed e-cadherin and formed well-oriented glands. We conclude that venous invasion is almost universal in pancreatic cancer, suggesting that even surgically resectable PDAC has access to the venous spaces and thus the ability to disseminate widely. Furthermore, we observe that sustained epithelial-mesenchymal transition is not required for venous invasion in pancreatic cancer.
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