Actinin-4 expression in primary and metastasized pancreatic ductal adenocarcinoma.
OBJECTIVE
Actinin-4 is an actin-bundling protein that probably has a tumor-promoting potential in several solid tumors. The present study analyzed the expression of actinin-4 in the pancreas, in localized and metastasized pancreatic ductal adenocarcinoma (PDAC), and the correlation with clinical outcome.


METHODS
Pancreatic ductal adenocarcinoma tissue from 38 patients, 15 lymph node and 10 liver metastases, normal pancreas, and 4 PDAC cell lines, were examined by immunohistochemistry, and actinin-4 expression was quantified by immunofluorescence analysis.


RESULTS
In the normal pancreas, actinin-4 was most prominently expressed in ductal cells. In PDAC, tumor cells exhibited strong but differential cytoplasmic immunoreactivity for actinin-4. A multivariate analysis revealed actinin-4 immunoreactivity, advanced age, and undifferentiated grade as significant prognostic factors associated with worse survival after PDAC resection. Cells metastasized to lymph nodes or to the liver exhibited no significant increase of actinin-4 compared with the primary tumors. A nuclear staining was observed neither in any of the PDAC samples nor in the 4 cell lines. In PDAC cells, actinin-4 localized to dynamic actin structures and to invadopodia.


CONCLUSIONS
Actinin-4 expression levels significantly correlate with worse survival after PDAC resection. Although actinin-4 has been reported to promote lymph node metastases, there was no enhanced expression in PDAC metastases.
Welsch
Thilo
T
Department of General, Visceral, and Transplant Surgery, University of Heidelberg, Heidelberg, Germany. thilo.welsch@med.uni-heidelberg.de
Keleg
Shereen
S
Bergmann
Frank
F
Bauer
Sonja
S
Hinz
Ulf
U
Schmidt
Jan
J
D000185:Actinin / Q000378:metabolism*; D000368:Aged; D015153:Blotting, Western; D021441:Carcinoma, Pancreatic Ductal / Q000378:metabolism / Q000556:secondary*; D045744:Cell Line, Tumor; D006801:Humans; D007150:Immunohistochemistry; D008113:Liver Neoplasms / Q000378:metabolism / Q000556:secondary*; D008207:Lymphatic Metastasis; D018613:Microscopy, Confocal; D008875:Middle Aged; D009367:Neoplasm Staging; D010179:Pancreas / Q000737:chemistry / Q000473:pathology; D010190:Pancreatic Neoplasms / Q000378:metabolism / Q000473:pathology*; D016019:Survival Analysis; D046888:Tissue Array Analysis
C111453:ACTN4 protein, human; D000185:Actinin