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Analysis of E-cadherin in diffuse-type gastric cancer using a mutation-specific monoclonal antibody

K F Becker1, E Kremmer, M Eulitz

  • 1Technische Universität München, Klinikum rechts der Isar, Institut für Pathologie, München, Germany. kf.becker@lrz.tum.de

The American Journal of Pathology
|December 14, 1999
PubMed

Insights

A new antibody, E-cad delta 9-1, specifically detects a mutant form of E-cadherin found in some gastric cancers. This discovery aids in the selective diagnosis and potential targeted therapy for these tumors.

Area of Science:

  • Oncology
  • Molecular Biology
  • Immunology

Background:

  • In-frame deletions in E-cadherin mRNA are common in diffuse-type gastric carcinomas.
  • Distinguishing mutant E-cadherin from wild-type using standard immunohistochemistry is challenging.
  • A specific E-cadherin variant lacking exon 9 arises from splice-site mutations.

Purpose of the Study:

  • To develop a specific monoclonal antibody to detect E-cadherin lacking exon 9.
  • To validate the antibody's specificity and utility in diagnosing gastric cancer.

Main Methods:

  • Generation of a rat monoclonal antibody (E-cad delta 9-1) targeting a unique fusion peptide.
  • Western blotting and immunohistochemistry on transfected cells to confirm antibody specificity.
  • Analysis of formalin-fixed, paraffin-embedded gastric carcinoma tissues and nontumorous samples.

Main Results:

  • E-cad delta 9-1 specifically recognized E-cadherin lacking exon 9, with no reaction to wild-type protein.
  • No immunoreactivity was found in nontumorous or embryonal tissues.
  • The antibody exclusively targeted tumor cells in gastric carcinoma specimens with mutant E-cadherin mRNA, identifying it in 13% of a retrospective series.

Conclusions:

  • E-cad delta 9-1 is a specific marker for E-cadherin variants lacking exon 9.
  • This antibody enables selective detection of tumor cells in diffuse-type gastric carcinomas.
  • The E-cad delta 9-1 antibody system offers potential for improved diagnosis and targeted therapy in a subset of gastric cancer patients.

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