Prognostic value of c-MET in head and neck cancer: A systematic review and meta-analysis of aggregate data

Oral Oncol. 2017 Nov:74:68-76. doi: 10.1016/j.oraloncology.2017.09.009. Epub 2017 Sep 27.

Abstract

Objectives: The hepatocyte growth factor (HGF)/mesenchymal-epithelial transition factor (c-MET) ligand/receptor axis has been implicated in pathogenesis of malignant diseases including squamous cell carcinoma of the head and neck (SCCHN). Overexpression of c-MET has been reported as a common molecular abnormality in SCCHN, although its prognostic and predictive value remains to be validated.

Methods: We systematically searched literature for studies evaluating c-MET expression on immunohistochemistry in newly diagnosed, non-metastatic SCCHN. The c-MET expressing cases were classified into three categories according to predefined cut-off values for positivity. Our aim was to assess the prevalence of c-MET expression and its relationship with selected clinicopathological variables.

Results: Twenty-eight studies with 2019 cases were included. Relative frequencies of c-MET expression above cut-off levels I, II, and III were 81.8%, 63.8%, and 46.2%, respectively. Differences between these three values were statistically significant (p<1.0×10-6). Above cut-off level II, c-MET positivity was associated with worse overall survival (p=4.0×10-6), positive nodal status (p=1.0×10-4), higher disease stage (p=7.0×10-4), older age (p=2.1×10-3), disease recurrence (p=2.0×10-2), and primary tumour localization in the oral cavity (p=2.3×10-2). Above cut-off level III, c-MET positivity was associated with worse disease-free or progression-free survival (p=9.0×10-6), p16 negativity (p=2.4×10-4), worse overall survival (p=4.0×10-4), positive epidermal growth factor receptor (EGFR) status (p=7.2×10-4), and larger primary tumours (p=4.6×10-3).

Conclusion: In SCCHN, immunohistochemical overexpression of c-MET above cut-off levels III and particularly II was associated with inferior survival outcomes and advanced disease. Moreover, it represents a promising predictive biomarker for c-MET targeting, yet the optimal scoring method remains to be defined.

Keywords: Head and neck cancer; Immunohistochemistry; Overexpression; Predictive factor; Prognostic factor; c-MET receptor.

Publication types

  • Meta-Analysis
  • Review
  • Systematic Review

MeSH terms

  • Carcinoma, Squamous Cell / genetics
  • Carcinoma, Squamous Cell / pathology*
  • Carcinoma, Squamous Cell / physiopathology
  • Epithelial-Mesenchymal Transition
  • Female
  • Head and Neck Neoplasms / genetics
  • Head and Neck Neoplasms / pathology*
  • Head and Neck Neoplasms / physiopathology
  • Humans
  • Immunohistochemistry
  • Male
  • Middle Aged
  • Prognosis
  • Proto-Oncogene Proteins c-met / genetics
  • Proto-Oncogene Proteins c-met / physiology*
  • Squamous Cell Carcinoma of Head and Neck
  • Survival Analysis

Substances

  • Proto-Oncogene Proteins c-met