A subgroup of patients with chronic pancreatitis overexpress the c-erb B-2 protooncogene.
OBJECTIVE
Chronic pancreatitis (CP) is a chronic condition associated with pancreatic fibrosis. A small subgroup of patients with CP develop enlargement of the head of the pancreas (EHP). This study examined some of the mechanisms that may lead to the development of EHP.


BACKGROUND
The c-erb B-2 protooncogene encodes a 185-kDa transmembrane growth factor receptor (p185) that regulates cell growth and differentiation.


METHODS
The authors analyzed c-erb B-2 expression in samples obtained from the head of the pancreas from 26 patients with CP (5 women, 21 men) using immunohistochemical and molecular technique. A diagnosis of CP with EHP was made when the vertical pancreatic head diameter was greater than 4 cm (14 patients), as determined by contrast-enhanced computed axial tomography scan. Pancreatic tissues from 15 healthy organ donors served as control subjects.


RESULTS
In all patients without EHP and in the healthy control subjects, p185 immunoreactivity was present at low levels. In contrast, strong p185 immunoreactivity was observed in acinar and ductal cells in all patients with EHP. By in situ hybridization, c-erb B-2 messenger ribonucleic acid (mRNA) grains were expressed at high levels in patients with CP with EHP in both ductal and acinar cells. Northern blot analysis demonstrated a 4.5-fold increase (p < 0.001) in c-erb B-2 mRNA levels in patients with EHP compared with patients without EHP and healthy control subjects. Southern blot analysis did not reveal c-erb B-2 gene amplification or rearrangement.


CONCLUSIONS
These findings indicate the c-erb B-2 is not overexpressed in most patients with CP. However, its overexpression in patients with CP with EHP suggest that c-erb B-2 may contribute to the pathophysiologic processes that lead to pancreatic head enlargement.
Friess
H
H
Department of Medicine, University of California, Irvine.
Yamanaka
Y
Y
Büchler
M
M
Hammer
K
K
Kobrin
M S
MS
Beger
H G
HG
Korc
M
M
D000293:Adolescent; D000328:Adult; D002908:Chronic Disease; D003593:Cytoplasm / Q000648:ultrastructure; D004247:DNA / Q000032:analysis / Q000235:genetics; D066246:ErbB Receptors / Q000032:analysis / Q000235:genetics*; D005260:Female; D005786:Gene Expression Regulation; D006801:Humans; D006984:Hypertrophy; D008297:Male; D008875:Middle Aged; D010179:Pancreas / Q000378:metabolism / Q000473:pathology; D010183:Pancreatic Ducts / Q000378:metabolism / Q000473:pathology; D010195:Pancreatitis / Q000235:genetics* / Q000473:pathology; D011518:Proto-Oncogene Proteins / Q000032:analysis / Q000235:genetics*; D011519:Proto-Oncogenes / Q000235:genetics*; D012313:RNA / Q000032:analysis / Q000235:genetics; D012333:RNA, Messenger / Q000032:analysis / Q000235:genetics; D018719:Erb-b2 Receptor Tyrosine Kinases
D004247:DNA; D066246:ErbB Receptors; D011518:Proto-Oncogene Proteins; D012313:RNA; D012333:RNA, Messenger; D018719:Erb-b2 Receptor Tyrosine Kinases