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

• Published in: Histopathology Vol. 45; no. 3; pp. 226 - 236
• Main Authors: Sipos, B, Hahn, D, Carceller, A, Piulats, J, Hedderich, J, Kalthoff, H, Goodman, S L, Kosmahl, M, Klöppel, G
• Format: Journal Article
• Language: English
• Published: Oxford, UK Blackwell Science Ltd 01-09-2004; Blackwell
• Subjects: Biological and medical sciences; fibronectin; gastrointestinal tumours; integrin; Investigative techniques, diagnostic techniques (general aspects); Medical sciences; Pathology. Cytology. Biochemistry. Spectrometry. Miscellaneous investigative techniques; tenascin; αvβ6; Adenocarcinoma; Immunohistochemistry; Tenascin; Stomach; Digestive system; αvβ6; Cell adhesion molecule; Malignant tumor; Monoclonal antibody; Medical screening; Gastrointestinal; Subunit; In vitro; Fibronectin; In vivo; Anatomic pathology; Regulation(control); Integrin; gastrointestinal tumours; Pancreas
• ISSN: 0309-0167; 1365-2559
• DOI: 10.1111/j.1365-2559.2004.01919.x

Aims : To analyse the expression of αvβ6, an epithelial integrin involved in wound healing and tumorigenesis, in various human carcinoma types.
Methods and results : A new monoclonal antibody to the human β6 subunit, 5C4, was used to locate αvβ6 in 157 cancers of gastroenteropancreatic and 21 of lung origin. The data were validated by analysis of αvβ6 extracted from histological sections. αvβ6 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 αvβ6 was seen in seven liver cell carcinomas and six neuroendocrine tumours. Well‐differentiated carcinomas expressed more β6 than poorly differentiated tumours. Peritumoral epithelial tissues where αvβ6‐expressing tumours arose also expressed αvβ6. There was no correlation between expression of αvβ6 and its ligands tenascin and fibronectin in pancreatic and gastric carcinomas. Spheroid formation by pancreatic carcinoma cell lines led to αvβ6 up‐regulation, but appeared independent of classical ligand binding to αvβ6.
Conclusions : Our findings indicate that: (i) αvβ6 is overexpressed in pancreatic adenocarcinomas; (ii) αvβ6‐positive carcinomas originate from αvβ6‐expressing tissues; (iii) αvβ6 expression in tumours seems to be regulated independently from that of its ligands tenascin and fibronectin; and (iv) in‐vitro overexpression of αvβ6 in pancreatic carcinoma cell lines accompanies spheroid formation.