title: Comparative analysis of tumorbiology and CD133 positivity in primary and recurrent pancreatic ductal adenocarcinoma.
abstract: In over 70% of the cases, patients with curative surgery and adjuvant chemotherapy for pancreatic ductal adenocarcinoma (PDAC) develop recurrent tumors. The cancer stem cell (CSC) hypothesis suggests that CSCs are chemoresistant and enriched in recurrent tumors. This study analyzes tumorbiology, expression of the metastasis-promoting CXCR4 and actinin-4, and of the CSC marker CD133 in primary and recurrent PDAC. Twenty-six patients underwent resection for primary and recurrent PDAC and most developed tumor recurrence within 2 years. In 81% the histologic tumor grade was unchanged. Immunohistochemistry could be performed with 15 pairs of primary and recurrent PDAC. The mean Ki-67 proliferation index increased (P = 0.06). About 30% of tumor cells were positive for CXCR4 and almost all tumor cells expressed actinin-4, but there were neither significant changes in the expression levels in recurrent PDAC, nor specifically enhanced levels in metastases. The prominent CD133 pattern was an apical membrane staining of inflammatorily altered, non-neoplastic ductal structures equally observed in primary and recurrent PDAC. The membrane CD133 positivity was consistently absent in neoplastic PDAC cells. Cytoplasmic CD133 positivity was extremely rare (0.85 and 0.34 cells/cm(2) in primary and recurrent PDAC, respectively; P = 0.07). Tumor grade is mainly unchanged and the expression of CXCR4, actinin-4 and CD133 are not enhanced in recurrent PDAC. The apical membrane CD133 positivity of normal and inflammatorily altered ductal structures and its lack in tumor cells bring the role of CD133 as a specific CSC marker in PDAC into question.
authors.affiliation: Department of General, Visceral and Transplant Surgery, University of Heidelberg, Im Neuenheimer Feld 110, 69120, Heidelberg, Germany. thilo.welsch@med.uni-heidelberg.de
authors.forename: Thilo
authors.initials: T
authors.lastname: Welsch
authors.forename: Shereen
authors.initials: S
authors.lastname: Keleg
authors.forename: Frank
authors.initials: F
authors.lastname: Bergmann
authors.forename: Luca
authors.initials: L
authors.lastname: Degrate
authors.forename: Sonja
authors.initials: S
authors.lastname: Bauer
authors.forename: Jan
authors.initials: J
authors.lastname: Schmidt
mesh_terms: D000071916:AC133 Antigen; D000368:Aged; D015703:Antigens, CD / Q000276:immunology*; D014408:Biomarkers, Tumor; D015153:Blotting, Western; D021441:Carcinoma, Pancreatic Ductal / Q000276:immunology / Q000473:pathology*; D006023:Glycoproteins / Q000276:immunology*; D006801:Humans; D007150:Immunohistochemistry; D018613:Microscopy, Confocal; D008875:Middle Aged; D010190:Pancreatic Neoplasms / Q000276:immunology / Q000473:pathology*; D010455:Peptides / Q000276:immunology*; D012008:Recurrence
chemical_list: D000071916:AC133 Antigen; D015703:Antigens, CD; D014408:Biomarkers, Tumor; D006023:Glycoproteins; C000606023:PROM1 protein, human; D010455:Peptides