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

- Immunohistochemical c-MET overexpression is common abnormality in head & neck cancer.
- Reported correlations of c-MET with clinicopathological variables are inconclusive.
- We performed a meta-analysis of 28 studies with 2019 untreated, non-metastatic cases.
- At least moderate expression was correlated with worse survival and advanced disease.
- Such immunohistochemical overexpression is a promising predictor for c-MET targeting.

ObjectivesThe 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.MethodsWe 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.ResultsTwenty-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).ConclusionIn 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.