Detailed tissue expression of bcl-2, bax, bak and bcl-x in the normal human pancreas and in chronic pancreatitis, ampullary and pancreatic ductal adenocarcinomas.
BACKGROUND
The aim of this study was to evaluate expression of the bcl-2 family of apoptosis regulating proteins in normal and diseased human pancreatic tissues.


METHODS
Expression of bcl-2, bax, bcl-x, bak and p53 was determined in formalin-fixed paraffin wax-embedded archival specimens of normal pancreatic tissue (n = 7), chronic pancreatitis (n = 7), pancreatic ductal adenocarcinoma (n = 23) and ampullary cancer (n = 7) by immunohistochemistry using specific antibodies.


RESULTS
In normal pancreas and chronic pancreatitis tissues, bcl-2, bax and bcl-x were predominantly expressed in ductal epithelial cells while p53 was not detected. In pancreatic ductal adenocarcinoma and ampullary cancer, bcl-2 was not detected compared with expression seen in normal acini (p < 0.01), minor (p < 0.001) and major ducts (p < 0.01), bax expression was reduced with respect to minor ducts (p < 0.01) but no different from normal acini or major ducts. bak and bcl-x were more strongly expressed in malignant epithelia compared with acini and major ducts but reduced when compared with minor ducts (p < 0.01). Overexpression of p53 was identified in 11 (48%) of 23 pancreatic adenocarcinomas and 4 (57%) of 7 ampullary cancers. Differential survival of individual patients was predicted by the relative level of bcl-x expression but not bax or bak, such that strong expression of bcl-x was associated with a median postoperative survival of 171 days when compared with 912 days for diminished expression (p < 0.001) of bcl-x.


CONCLUSIONS
Pancreatic and ampullary cancer are associated with absent bcl-2 expression. bax, bak and bcl-x expression was reduced compared with normal minor ducts whilst bak and bcl-x expression was increased when compared with major ducts. bcl-x expression correlates with survival following resection and may represent a potential prognosis marker.
Evans
J D
JD
Department of Surgery, University of Liverpool, Royal Liverpool University Hospital, Liverpool, UK.
Cornford
P A
PA
Dodson
A
A
Greenhalf
W
W
Foster
C S
CS
Neoptolemos
J P
JP
D000230:Adenocarcinoma / Q000401:mortality / Q000473:pathology; D017209:Apoptosis; D021441:Carcinoma, Pancreatic Ductal / Q000401:mortality / Q000473:pathology*; D006801:Humans; D007150:Immunohistochemistry; D008565:Membrane Proteins / Q000032:analysis*; D010179:Pancreas / Q000166:cytology* / Q000502:physiology; D010190:Pancreatic Neoplasms / Q000401:mortality / Q000473:pathology*; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000032:analysis*; D015996:Survival Rate; D013997:Time Factors; D050998:bcl-2 Homologous Antagonist-Killer Protein; D051020:bcl-X Protein
C494772:BAK1 protein, human; C494811:BCL2L1 protein, human; D008565:Membrane Proteins; D019253:Proto-Oncogene Proteins c-bcl-2; D050998:bcl-2 Homologous Antagonist-Killer Protein; D051020:bcl-X Protein