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Three-dimensional visualization of cleared human pancreas cancer reveals that sustained epithelial-to-mesenchymal transition is not required for venous invasion

Modern Pathology Nov 17, 2019

Hong SM, Jung DJ, Kiemen A, et al. - Fifty-two thick slabs 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 in order to identify the patterns of venous invasion in pancreatic cancer. Compared with that in conventional 2D slide assessment (75%), venous invasion was discovered more often in 3D (88%). Pancreatic cancer cells crossing the walls of veins at various points were shown by 3D visualization, frequently at points where preexisting capillary structures bridge the blood vessels. A ductal morphology (cohesive cells forming tubes) was frequently retained by the neoplastic cells since they improved from a stromal to intravenous location. However, immunolabeling with antibodies to e-cadherin exhibited focal loss of expression at the leading edges of the cancers, the neoplastic cells within veins expressed e-cadherin and created well-oriented glands. In summary, in pancreatic cancer, venous invasion is nearly universal, implying that even surgically resectable PDAC has access to the venous spaces and hence, the ability to disseminate extensively. Moreover, it was noted that for venous invasion in pancreatic cancer, no need of sustained epithelial–mesenchymal transition is observed.
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