Analysis of E-Cadherin in Diffuse-Type Gastric Cancer Using a Mutation-Specific Monoclonal Antibody
1999; Elsevier BV; Volume: 155; Issue: 6 Linguagem: Inglês
10.1016/s0002-9440(10)65497-1
ISSN1525-2191
AutoresKarl‐Friedrich Becker, Elisabeth Kremmer, Manfred Eulitz, Ingrid Becker, Gabriele Handschuh, Christoph Schuhmacher, Wolfram Müller, Helmut E. Gabbert, Atsushi Ochiai, Setsuo Hirohashi, Heinz Höfler,
Tópico(s)Kruppel-like factors research
ResumoIn-frame deletions from the E-cadherin mRNA, coding for a homophilic cell adhesion molecule, are characteristic for diffuse-type gastric carcinomas. Using immunohistochemical analysis the mutant form cannot be distinguished from normal E-cadherin, making results difficult to interpret. In this study, a rat monoclonal antibody, designated E-cad delta 9-1, was generated against a peptide spanning the fusion junction region between exons 8 and 10. This new epitope is present in an E-cadherin variant that lacks exon 9 from the mRNA due to different splice-site gene mutations. Using Western blotting and immunohistochemistry of E-cadherin-transfected cells, we demonstrate that E-cad delta 9-1 specifically reacts with E-cadherin lacking exon 9 but not with the wild-type protein. No immunoreactivity was observed in 31 nontumorous and embryonal tissues analyzed. In gastric carcinoma specimens known to express mutant E-cadherin mRNA lacking exon 9, E-cad delta 9-1 targets exclusively tumor cells in routine formalin-fixed and paraffin-embedded material from biopsies, primary tumors, and lymph node metastases. In a retrospective series of 172 diffuse-type gastric carcinomas expressing E-cadherin, E-cad delta 9-1 reacted with 22 tumors (13%). This new tumor marker-monoclonal antibody system could open novel avenues for selective diagnosis and specific therapy of a subgroup of diffuse-type gastric cancer patients.
Referência(s)