ErbB-4 mRNA expression is decreased in non-metastatic pancreatic cancer

The erbB-4 gene encodes a detected receptor protein that possesses intrinsi c tyrosine kinase activity and belongs to the family of the epidermal growt h factor receptor (EGFR); erbB-4 is stimulated by the heregulins and betace llulin, which enables this receptor to form heterodimers with erbB-2, a pre requisite for erbB-2 activation. Because the expression of erbB-4 mRNA is g enerally low in the pancreas, quantitative reverse transcriptase-polymerase chain reaction (RT-PCR) was used to determine the erbB-4 levels in human n ormal and cancerous pancreatic tissue. Our results show that the mRNA expre ssion of this receptor is 6-fold decreased in the nonmetastatic stages of p ancreatic cancer when compared to tumors with lymph node or distant metasta ses or to the normal pancreas. In addition, immunohistochemistry demonstrat ed that in the normal pancreas, the erbB-4 antigen was predominantly presen t in the cell membrane and cytoplasm of the ductal and acinar cells and at a much Tower level, in islet cells. In pancreatic cancer, 61 of 75 samples exhibited weak to moderate immunoreactivity for erbB-4 in the tumor cells. Moreover, in the peri-tumorous region with chronic pancreatitis-like morpho logical changes, there was weak-to-moderate erbB-4 immunostaining in small ductules and degenerating acinar cells. Uni- and multivariate survival anal yses using as variables age, sex, stage of cancer, histo-pathological gradi ng, and erbB-4 immunoreactivity, revealed a significant effect for stage of cancer (p < 0.01) whereby the risk of dying was 2.3 times higher in patien ts with metastases than in patients without. However, the level of erbB-4 i mmunoreactivity in pancreatic cancer cells had no influence on patient surv ival. (C) 1999 Wiley-Liss, Inc.