Comparative analysis of the EGF-receptor family in pancreatic cancer: expression of HER-4 correlates with a favourable tumor stage.
BACKGROUND
Of major interest for a better molecular understanding of pancreatic cancer is the EGF receptor family. While HER-1 (EGF-receptor) and HER-2 have been extensively studied, little is known about the clinical significance of HER-3 and especially HER-4 expression.


METHODS
We investigated the expression of HER-1, HER-2, HER-3 and HER-4 in 11 pancreatic cancer cell lines using FACS-analysis and determined expression and overexpression of these receptors in 24 pancreatic cancer specimens. Therefore, we used two different immunostaining techniques: a highly sensitive streptavidin-biotin method showed receptor expression while an approximatly 10-fold less sensitive indirect immunperoxidase technique determined receptor-overexpression.


RESULTS
HER-1 and HER-2 were expressed by all 11 pancreatic cancer cell lines, HER-3 was found in 82% and HER-4 in 54% of the cell lines. Low levels of HER-1, HER-2 and HER-3 were detected in all tumor samples but overexpression was only found in 33%, 25% and 50% of the cases, respectively. HER-4 was expressed by 37% of the tumor specimens but overexpression was seen in one patient only. HER-1 and HER-2 overexpression increased in parallel with the tumor stage and R0-resected tumors showed significantly less often overexpression compared to R1/R2 resected tumors (p < 0.05). In contrast, 54% of the R0-resected vs. 18% of the R1/R2 resected tumors showed HER-4 expression (p = 0.07) and HER-4 was exclusively found in non-metastatic tumors (p = 0.0149).


CONCLUSIONS
Our data indicate that HER-1 and HER-2 overexpression contributes to a more aggressive phenotype. In contrast, the lack of HER-4 expression might increase the metastatic capacity of pancreatic cancer cells.
Thybusch-Bernhardt
A
A
Department of Pediatric Surgery, University Hospital Lübeck, Lübeck, Germany.
Beckmann
S
S
Juhl
H
H
D014408:Biomarkers, Tumor / Q000032:analysis*; D066246:ErbB Receptors / Q000032:analysis / Q000235:genetics*; D005260:Female; D019084:Fluorescent Antibody Technique, Indirect; D005784:Gene Amplification; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D007150:Immunohistochemistry; D008297:Male; D009367:Neoplasm Staging; D010190:Pancreatic Neoplasms / Q000235:genetics* / Q000473:pathology*; D011336:Probability; D011379:Prognosis; D018719:Erb-b2 Receptor Tyrosine Kinases / Q000235:genetics; D020893:Receptor, ErbB-3 / Q000235:genetics; D066247:Receptor, ErbB-4; D012494:Sampling Studies; D012680:Sensitivity and Specificity; D014407:Tumor Cells, Cultured
D014408:Biomarkers, Tumor; D066246:ErbB Receptors; D018719:Erb-b2 Receptor Tyrosine Kinases; D020893:Receptor, ErbB-3; D066247:Receptor, ErbB-4; C587689:ERBB4 protein, human