Expression of the "stem cell marker" CD133 in pancreas and pancreatic ductal adenocarcinomas.
BACKGROUND
It has been suggested that a small population of cells with unique self-renewal properties and malignant potential exists in solid tumors. Such "cancer stem cells" have been isolated by flow cytometry, followed by xenograft studies of their tumor-initiating properties. A frequently used sorting marker in these experiments is the cell surface protein CD133 (prominin-1). The aim of this work was to examine the distribution of CD133 in pancreatic exocrine cancer.


METHODS
Fifty-one cases of pancreatic ductal adenocarcinomas were clinically and histopathologically evaluated, and immunohistochemically investigated for expression of CD133, cytokeratin 19 and chromogranin A. The results were interpreted on the background of CD133 expression in normal pancreas and other normal and malignant human tissues.


RESULTS
CD133 positivity could not be related to a specific embryonic layer of organ origin and was seen mainly at the apical/endoluminal surface of non-squamous, glandular epithelia and of malignant cells in ductal arrangement. Cytoplasmic CD133 staining was observed in some non-epithelial malignancies. In the pancreas, we found CD133 expressed on the apical membrane of ductal cells. In a small subset of ductal cells and in cells in centroacinar position, we also observed expression in the cytoplasm. Pancreatic ductal adenocarcinomas showed a varying degree of apical cell surface CD133 expression, and cytoplasmic staining in a few tumor cells was noted. There was no correlation between the level of CD133 expression and patient survival.


CONCLUSIONS
Neither in the pancreas nor in the other investigated organs can CD133 membrane expression alone be a criterion for "stemness". However, there was an interesting difference in subcellular localization with a minor cell population in normal and malignant pancreatic tissue showing cytoplasmic expression. Moreover, since CD133 was expressed in shed ductal cells of pancreatic tumors and was found on the surface of tumor cells in vessels, this molecule may have a potential as clinical marker in patients suffering from pancreatic cancer.
Immervoll
Heike
H
Section for Pathology, Gade Institute, University of Bergen, Bergen, Norway. heike.immervoll@helse-bergen.no <heike.immervoll@helse-bergen.no>
Hoem
Dag
D
Sakariassen
Per Øystein
PØ
Steffensen
Ole Johnny
OJ
Molven
Anders
A
D000071916:AC133 Antigen; D015703:Antigens, CD / Q000378:metabolism*; D014408:Biomarkers, Tumor / Q000378:metabolism*; D021441:Carcinoma, Pancreatic Ductal / Q000378:metabolism*; D002462:Cell Membrane / Q000378:metabolism; D053379:Chromogranin A / Q000378:metabolism; D003593:Cytoplasm / Q000378:metabolism; D004847:Epithelial Cells / Q000378:metabolism; D006023:Glycoproteins / Q000378:metabolism*; D006801:Humans; D007150:Immunohistochemistry; D053539:Keratin-19 / Q000378:metabolism; D010179:Pancreas / Q000378:metabolism*; D010190:Pancreatic Neoplasms / Q000378:metabolism*; D010455:Peptides / Q000378:metabolism*; D012016:Reference Values; D013234:Stem Cells / Q000378:metabolism; D014018:Tissue Distribution
D000071916:AC133 Antigen; D015703:Antigens, CD; D014408:Biomarkers, Tumor; D053379:Chromogranin A; D006023:Glycoproteins; D053539:Keratin-19; C000606023:PROM1 protein, human; D010455:Peptides