Immunohistochemical screening for β6-integrin subunit expression in adenocarcinomas using a novel monoclonal antibody reveals strong up-regulation in pancreatic ductal adenocarcinomas in vivo and in vitro

Aims: To analyse the expression of alpha(v)beta(6), an epithelial integrin involved in wound healing and tumorigenesis, in various human carcinoma types. Methods and results: A new monoclonal antibody to the human beta(6) subunit, 5C4, was used to locate alpha(v)beta(6) in 157 cancers of gastroenteropancreatic and 21 of lung origin. The data were validated by analysis of alpha(v)beta(6) extracted from histological sections. alpha(v)beta(6) integrin showed strongest expression in 34 pancreatic ductal adenocarcinomas (mean score 2.88 +/- 0.52), followed by 24 intestinal-type gastric carcinomas (1.45 +/- 1.06) and eight lung adenocarcinomas (1.37 +/- 1.1). Moderate expression was found in 31 diffuse-type gastric carcinomas (0.94 +/- 0.83), seven duodenal adenocarcinomas (0.8 +/- 1.34) and 26 colorectal adenocarcinomas (0.76 +/- 0.71). Little alpha(v)beta(6) was seen in seven liver cell carcinomas and six neuroendocrine tumours. Well-differentiated carcinomas expressed more beta(6) than poorly differentiated tumours. Peritumoral epithelial tissues where alpha(v)beta(6)-expressing tumours arose also expressed alpha(v)beta(6). There was no correlation between expression of alpha(v)beta(6) and its ligands tenascin and fibronectin in pancreatic and gastric carcinomas. Spheroid formation by pancreatic carcinoma cell lines led to alpha(v)beta(6) up-regulation, but appeared independent of classical ligand binding to alpha(v)beta(6). Conclusions: Our findings indicate that: (i) alpha(v)beta(6) is overexpressed in pancreatic adenocarcinomas; (ii) alpha(v)beta(6)-positive carcinomas originate from alpha(v)beta(6)-expressing tissues; (iii) alpha(v)beta(6) expression in tumours seems to be regulated independently from that of its ligands tenascin and fibronectin; and (iv) in-vitro overexpression of alpha(v)beta(6) in pancreatic carcinoma cell lines accompanies spheroid formation.