A novel multipurpose monoclonal antibody for evaluating human c-Met expression in preclinical and clinical settings

Appl Immunohistochem Mol Morphol. 2009 Jan;17(1):57-67. doi: 10.1097/PAI.0b013e3181816ae2.


The inappropriate expression of the c-MET cell surface receptor in many human solid tumors necessitates the development of companion diagnostics to identify those patients who could benefit from c-MET targeted therapies. Tumor tissues are formalin fixed and paraffin embedded (FFPE) for histopathologic evaluation, making the development of an antibody against c-MET that accurately and reproducibly detects the protein in FFPE samples an urgent need. We have developed a monoclonal antibody (mAb), designated MET4, from a panel of MET-avid mAbs, based on its specific staining pattern in FFPE preparations. The accuracy of MET4 immunohistochemistry (MET4-IHC) was assessed by comparing MET4-IHC in FFPE cell pellets with immunoblotting analysis. The technical reproducibility of MET4-IHC possessed a percentage coefficient of variability of 6.25% in intra-assay and interassay testing. Comparison with other commercial c-MET antibody detection reagents demonstrated equal specificity and increased sensitivity for c-MET detection in prostate tissues. In cohorts of ovarian cancers and gliomas, MET4 reacted with ovarian cancers of all histologic subtypes (strong staining in 25%) and with 63% of gliomas. In addition, MET4 bound c-MET on the surfaces of cultured human cancer cells and tumor xenografts. In summary, the MET4 mAb accurately and reproducibly measures c-MET expression by IHC in FFPE tissues and can be used for molecular imaging in vivo. These properties encourage further development of MET4 as a multipurpose molecular diagnostics reagent to help to guide appropriate selection of patients being considered for treatment with c-MET-antagonistic drugs.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't
  • Validation Study

MeSH terms

  • Antibodies, Monoclonal*
  • Biomarkers, Tumor / analysis*
  • Biomarkers, Tumor / standards
  • Female
  • Formaldehyde
  • Glioma
  • Humans
  • Immunohistochemistry
  • Male
  • Neoplasms / chemistry
  • Neoplasms / diagnosis
  • Neoplasms / pathology*
  • Ovarian Neoplasms
  • Paraffin Embedding
  • Proto-Oncogene Proteins c-met / analysis*
  • Tissue Fixation


  • Antibodies, Monoclonal
  • Biomarkers, Tumor
  • Formaldehyde
  • Proto-Oncogene Proteins c-met