Absent and abundant MET immunoreactivity is associated with poor prognosis of patients with oral and oropharyngeal squamous cell carcinoma

De Herdt, M. J., Willems, S. M., van der Steen, B., Noorlag, R., Verhoef, E. I., van Leenders, G. J. L. H., van Es, R. J. J., KoljenoviÄ, S., Baatenburg de Jong, R. J. & Looijenga, L. H. J., 2016, In : Oncotarget. 7, 11, p. 13167-13181 15 p.

Research output: Contribution to journalArticleAcademicpeer-review

  • Maria J De Herdt
  • Stefan M Willems
  • Berdine van der Steen
  • Rob Noorlag
  • Esther I Verhoef
  • Geert J L H van Leenders
  • Robert J J van Es
  • Senada KoljenoviÄ
  • Robert J Baatenburg de Jong
  • Leendert H J Looijenga

Although the receptor tyrosine kinase (RTK) MET is widely expressed in head and neck squamous cell carcinoma (HNSCC), its prognostic value remains unclear. This might be due to the use of a variety of antibodies and scoring systems. Here, the reliability of five commercial C-terminal MET antibodies (D1C2, CVD13, SP44, C-12 and C-28) was evaluated before examining the prognostic value of MET immunoreactivity in HNSCC. Using cancer cell lines, it was shown that D1C2 and CVD13 specifically detect MET under reducing, native and formalin-fixed paraffin-embedded (FFPE) conditions. Immunohistochemical staining of routinely FFPE oral SCC with D1C2 and CVD13 demonstrated that D1C2 is most sensitive in the detection of membranous MET. Examination of membranous D1C2 immunoreactivity with 179 FFPE oral and oropharyngeal SCC - represented in a tissue microarray - illustrated that staining is either uniform (negative or positive) across tumors or differs between a tumor's center and periphery. Ultimately, statistical analysis revealed that D1C2 uniform staining is significantly associated with poor 5-year overall and disease free survival of patients lacking vasoinvasive growth (HR = 3.019, p < 0.001; HR = 2.559, p < 0.001). These findings might contribute to reliable stratification of patients eligible for treatment with biologicals directed against MET.

Original languageEnglish
Pages (from-to)13167-13181
Number of pages15
Issue number11
Publication statusPublished - 2016
Externally publishedYes


  • Adult, Aged, Aged, 80 and over, Antibodies, Monoclonal, Antibody Specificity, Biomarkers, Tumor/analysis, Carcinoma, Squamous Cell/metabolism, Disease-Free Survival, Female, Head and Neck Neoplasms/metabolism, Humans, Immunohistochemistry/methods, Kaplan-Meier Estimate, Male, Middle Aged, Mouth Neoplasms/metabolism, Oropharyngeal Neoplasms/metabolism, Prognosis, Proto-Oncogene Proteins c-met/analysis, Reproducibility of Results, Squamous Cell Carcinoma of Head and Neck

ID: 124017000