Is serous cystadenoma of the pancreas a model of clear-cell-associated angiogenesis and tumorigenesis?
BACKGROUND
Similar to the other von Hippel-Lindau (VHL)-related tumors such as renal cell carcinomas and capillary hemangioblastomas, serous cystadenomas (SCAs) of the pancreas are also characterized by clear cells. Over the years, we have also noticed that the tumor epithelium shows a prominent capillary network.


METHODS
Eighteen cases of SCA were reviewed histologically, and immunohistochemical analysis was performed for CD31 and vascular endothelial growth factor (VEGF) as well as the molecules implicated in clear-cell tumorigenesis: GLUT-1, hypoxia-inducible factor-1 (HIF-1alpha), and carbonic anhydrase IX (CA IX).


RESULTS
There was an extensively rich capillary network that appears almost intraepithelially in all cases of SCA, which was confirmed by CD31 stain that showed, on average, 26 capillaries per every 100 epithelial cells. VEGF expression was identified in 10/18 cases. Among the clear-cell tumorigenesis markers, CA IX was detected in all cases, GLUT-1 and HIF-1alpha in most cases.


CONCLUSIONS
As in other VHL-related clear-cell tumors, there is a prominent capillary network immediately adjacent to the epithelium of SCA, confirming that the clear-cell- angiogenesis association is also valid for this tumor type. Molecules implicated in clear-cell tumorigenesis are also consistently expressed in SCA. This may have biologic and therapeutic implications, especially considering the rapidly evolving drugs against these pathways. More importantly, SCA may also serve as a model of clear-cell-associated angiogenesis and tumorigenesis, and the information gained from this tumor type may also be applicable to other clear-cell tumors.
Thirabanjasak
Duangpen
D
Department of Pathology, Wayne State University and Karmanos Cancer Institute, Detroit, MI, USA.
Basturk
Olca
O
Altinel
Deniz
D
Cheng
Jeanette D
JD
Adsay
N Volkan
NV
D000328:Adult; D000368:Aged; D018293:Cystadenoma, Serous / Q000098:blood supply / Q000473:pathology*; D005260:Female; D051272:Glucose Transporter Type 1 / Q000378:metabolism; D006801:Humans; D051795:Hypoxia-Inducible Factor 1, alpha Subunit / Q000096:biosynthesis; D007150:Immunohistochemistry; D008297:Male; D008875:Middle Aged; D009389:Neovascularization, Pathologic; D010190:Pancreatic Neoplasms / Q000098:blood supply / Q000209:etiology / Q000473:pathology*; D019408:Platelet Endothelial Cell Adhesion Molecule-1 / Q000378:metabolism; D042461:Vascular Endothelial Growth Factor A / Q000378:metabolism
D051272:Glucose Transporter Type 1; D051795:Hypoxia-Inducible Factor 1, alpha Subunit; D019408:Platelet Endothelial Cell Adhesion Molecule-1; C467484:VEGFA protein, human; D042461:Vascular Endothelial Growth Factor A