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.
| Original language | English (US) |
|---|---|
| Journal | Modern Pathology |
| DOIs | |
| State | Accepted/In press - Jan 1 2019 |
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ASJC Scopus subject areas
- Pathology and Forensic Medicine
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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. / Hong, Seung Mo; Jung, Dong Jun; Kiemen, Ashley; Gaida, Matthias M.; Yoshizawa, Tadashi; Braxton, Alicia M.; Noë, Michaël; Lionheart, Gemma; Oshima, Kiyoko; Thompson, Elizabeth D.; Burkhart, Richard; Wu, Pei Hsun; Wirtz, Denis; Hruban, Ralph H.; Wood, Laura D.
In: Modern Pathology, 01.01.2019.Research output: Contribution to journal › Article
}
TY - JOUR
T1 - Three-dimensional visualization of cleared human pancreas cancer reveals that sustained epithelial-to-mesenchymal transition is not required for venous invasion
AU - Hong, Seung Mo
AU - Jung, Dong Jun
AU - Kiemen, Ashley
AU - Gaida, Matthias M.
AU - Yoshizawa, Tadashi
AU - Braxton, Alicia M.
AU - Noë, Michaël
AU - Lionheart, Gemma
AU - Oshima, Kiyoko
AU - Thompson, Elizabeth D.
AU - Burkhart, Richard
AU - Wu, Pei Hsun
AU - Wirtz, Denis
AU - Hruban, Ralph H.
AU - Wood, Laura D.
PY - 2019/1/1
Y1 - 2019/1/1
N2 - 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.
AB - 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.
UR - http://www.scopus.com/inward/record.url?scp=85074827773&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=85074827773&partnerID=8YFLogxK
U2 - 10.1038/s41379-019-0409-3
DO - 10.1038/s41379-019-0409-3
M3 - Article
C2 - 31700162
AN - SCOPUS:85074827773
JO - Modern Pathology
JF - Modern Pathology
SN - 0893-3952
ER -