HER-family gene amplification and expression in resected pancreatic cancer.
OBJECTIVE
Despite surgical resection, pancreatic cancer carries a poor prognosis. In search for new molecular therapeutic targets, we investigated the expression of the HER-family and gene amplification of HER-2 in pancreatic adenocarcinomas of different stages.


METHODS
Tissue of 45 resected patients was analyzed for all HER-family 1-4 expression by immunohistochemistry and HER-2 gene amplification was assessed by multiplex ligation-dependent probe amplification and chromogenic in situ hybridization. The type of surgery, location, stage and grade of the tumor, as well as involvement of the resection margins were correlated with HER-expressions and univariate and multivariate survival analysis performed.


RESULTS
Normal pancreatic tissue lacked HER1-2 expression, but did show HER3-4 expression. In cancers, no membranous overexpression of HER-1 and HER-2 was seen nor gene amplification of HER-2 found. HER-3, HER-4 is physiologically expressed in the normal pancreas and loss of cytoplasmic HER-3 and HER-4 expression was seen in 33/45 (73%) and 8/45 (18%) of pancreatic cancers. Cytoplasmic HER-3 expression decreased from early to late stage (p=0.05). HER-4 expression was not associated with survival, stage or tumor grade. There were no statistically significant differences in HER1-4 expression between the papilla of Vater (n=13) and non-papilla cancers (n=32). Multivariate survival analysis showed only stage to be of independent prognostic value (p=0.015).


CONCLUSIONS
HER-1 and HER-2 are not overexpressed in pancreatic cancers. HER-3 and HER-4 are expressed in the normal pancreas but expression is lost in pancreatic cancer. HER-targeted therapy in pancreatic cancer is not supported by HER-expression of the tumor.
te Velde
E A
EA
Department of Surgery, University Medical Centre Utrecht, Heidelberglaan 100, 3584 CX, The Netherlands.
Franke
A C
AC
van Hillegersberg
R
R
Elshof
S M
SM
de Weger
R W
RW
Borel Rinkes
I H M
IH
van Diest
P J
PJ
D000230:Adenocarcinoma / Q000235:genetics* / Q000378:metabolism* / Q000473:pathology / Q000628:therapy; D000328:Adult; D000368:Aged; D016503:Drug Delivery Systems; D066246:ErbB Receptors / Q000378:metabolism*; D005260:Female; D018734:Genes, erbB-2; D006801:Humans; D007150:Immunohistochemistry; D008297:Male; D008875:Middle Aged; D015999:Multivariate Analysis; D021141:Nucleic Acid Amplification Techniques; D010190:Pancreatic Neoplasms / Q000235:genetics* / Q000378:metabolism* / Q000473:pathology / Q000628:therapy; D018719:Erb-b2 Receptor Tyrosine Kinases / Q000378:metabolism*; D020893:Receptor, ErbB-3 / Q000378:metabolism*; D016019:Survival Analysis
D066246:ErbB Receptors; D018719:Erb-b2 Receptor Tyrosine Kinases; D020893:Receptor, ErbB-3