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 so me of the mechanisms that may lead to the development of EHP. Summary Background Data The c-erb B-2 protooncogene encodes a 185-kDa transmem brane growth factor receptor (p185) that regulates cell growth and dif ferentiation. Methods The authors analyzed c-erb B-2 expression in sam ples obtained from the head of the pancreas from 26 patients with CP ( 5 women, 21 men) using immunohistochemical and molecular techniques. A diagnosis of CP with EHP was made when the vertical pancreatic head d iameter was greater than 4 cm (14 patients), as determined by contrast -enhanced computed axial tomography scan. Pancreatic tissues from 15 h ealthy organ donors served as control subjects. Results In all patient s without EHP and in the healthy control subjects, p185 immunoreactivi ty was present at low levels. In contrast, strong p185 immunoreactivit y was observed in acinar and ductal cells in all patients with EHP. By in situ hybridization, c-erb B-2 messenger ribonucleic acid (mRNA) gr ains were expressed at high levels in patients with CP with EHP in bot h ductal and acinar cells. Northern blot analysis demonstrated a 4.5-f old increase (p<0.001) in c-erb B-2 mRNA levels in patients with EHP c ompared with patients without EHP and healthy control subjects. Southe rn blot analysis did not reveal c-erb B-2 gene amplification or rearra ngement. Conclusions These findings indicate the c-erb B-2 is not over expressed in most patients with CP. However, its overexpression in pat ients with CP with EHP suggest that c-erb B-2 may contribute to the pa thophysiologic processes that lead to pancreatic head enlargement.