ErbB2 growth factor receptor, a marker for neuroendocrine cells?
OBJECTIVE
The overexpression of ErbB2 in pancreatic cancer has been reported with a varying incidence ranging between 1 and 80%. Our routine examination, however, revealed a consistently strong immunoreactivity of three anti-ErbB2 growth factor receptor antibodies in pancreatic islets and intrapancreatic ganglia. To validate our findings and to understand the reasons for the reported differences in the frequency of ErbB2 overexpression in pancreatic cancer, the following studies were performed.


METHODS
Tissue samples from 12 normal pancreata, 7 surgical chronic pancreatitis cases, 21 primary pancreatic adenocarcinomas, 9 metastatic pancreatic adenocarcinomas, and 4 islet cell tumors were subjected to immunohistochemical examination using antibodies from three manufacturers. Cultured human islet cells and pancreatic cancer cell lines, as well as samples from the gastrointestinal tract, the CNS, and the adrenal gland were included in the study. For comparison, mammary cancer tissue and mammary cancer cells, as well as selected tissues from Syrian golden hamsters, were used. To verify the results, Western blot and Northern slot-blot analyses were performed.


RESULTS
Pancreatic cancer cells, in vitro and in vivo, showed a remarkable heterogeneity in the immunostaining of ErbB2, ranging from very faintly to strongly stained. On the other hand, in both humans and hamsters, a consistently strong immunostaining was found in the Langerhans' islets, in the ganglia of intrapancreatic and extrapancreatic nerves, as well as in the CNS, spinal cord and adrenal gland.


CONCLUSIONS
ErbB2 appears to play an important role in neuroendocrine tissues and is probably involved in the development and functional regulation of these cells. The concomitant expression of these factors and islet cell hormones very likely results in the activation of multiple growth-promoting pathways in pancreatic cancer and its aggressive behavior.
Standop
Jens
J
UNMC Eppley Institute, University of Nebraska Medical Center, Omaha, NE, USA. standop@uni-bonn.de
Andrianifahanana
Mahefatiana
M
Moniaux
Nicolas
N
Schneider
Matthias
M
Ulrich
Alexis
A
Brand
Randall E
RE
Wisecarver
James L
JL
Bridge
Julia A
JA
Büchler
Markus W
MW
Adrian
Thomas E
TE
Batra
Surinder K
SK
Pour
Parviz M
PM
D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000818:Animals; D015415:Biomarkers / Q000378:metabolism; D002648:Child; D002675:Child, Preschool; D006224:Cricetinae; D005260:Female; D015870:Gene Expression; D006801:Humans; D007223:Infant; D008297:Male; D008647:Mesocricetus; D008875:Middle Aged; D009490:Neurosecretory Systems / Q000378:metabolism; D010179:Pancreas / Q000166:cytology / Q000378:metabolism*; D010190:Pancreatic Neoplasms / Q000378:metabolism* / Q000473:pathology; D018719:Erb-b2 Receptor Tyrosine Kinases / Q000378:metabolism*
D015415:Biomarkers; D018719:Erb-b2 Receptor Tyrosine Kinases