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

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.

• Authors: Petr Szturz, Marie Budíková, Jan B Vermorken, Ivana Horová, Břetislav Gál, Eric Raymond, Armand de Gramont, Sandrine Faivre
• Journal: Oral oncology (Oral Oncol) Vol. 74 Pg. 68-76 (11 2017) ISSN: 1879-0593 [Electronic] England
• PMID: 29103754 (Publication Type: Journal Article, Meta-Analysis, Review, Systematic Review)
• Copyright: Copyright © 2017 Elsevier Ltd. All rights reserved.

Chemical References

• Proto-Oncogene Proteins c-met

Topics

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