Petr Szturz1, Marie Budíková2, Jan B Vermorken3, Ivana Horová2, Břetislav Gál4, Eric Raymond5, Armand de Gramont6, Sandrine Faivre7. 1. Department of Internal Medicine, Hematology, and Oncology, University Hospital Brno, Brno, Czech Republic; School of Medicine, Masaryk University, Brno, Czech Republic. Electronic address: szturz@gmail.com. 2. Department of Mathematics and Statistics, Faculty of Science, Masaryk University, Brno, Czech Republic. 3. Department of Medical Oncology, Antwerp University Hospital, Edegem, Belgium; Faculty of Medicine and Health Sciences, University of Antwerp, Antwerp, Belgium. 4. School of Medicine, Masaryk University, Brno, Czech Republic; Department of Otorhinolaryngology and Head and Neck Surgery, St. Anne's Faculty Hospital Brno, Brno, Czech Republic. 5. Department of Oncology, Hospital Paris Saint-Joseph, Paris, France. 6. AFR Oncology, Boulogne-Billancourt, France. 7. Department of Oncology, Bichat-Beaujon University Hospital, Paris, France.
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.
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: Sara E Kochanny; Francis P Worden; Douglas R Adkins; Dean W Lim; Julie E Bauman; Stephanie A Wagner; Ryan J Brisson; Theodore G Karrison; Walter M Stadler; Everett E Vokes; Tanguy Y Seiwert Journal: Cancer Date: 2020-02-19 Impact factor: 6.860
Authors: Anita Thomas; Kimberly Sue Slade; Roman A Blaheta; Sascha D Markowitsch; Philipp Stenzel; Katrin E Tagscherer; Wilfried Roth; Mario Schindeldecker; Martin Michaelis; Florian Rothweiler; Jaroslav Cinatl; Robert Dotzauer; Olesya Vakhrusheva; Maarten Albersen; Axel Haferkamp; Eva Juengel; Jindrich Cinatl; Igor Tsaur Journal: Cancers (Basel) Date: 2022-03-25 Impact factor: 6.639
Authors: Verena Boschert; Nicola Klenk; Alexander Abt; Sudha Janaki Raman; Markus Fischer; Roman C Brands; Axel Seher; Christian Linz; Urs D A Müller-Richter; Thorsten Bischler; Stefan Hartmann Journal: Int J Mol Sci Date: 2020-01-11 Impact factor: 5.923
Authors: Maria J De Herdt; Berdine van der Steen; Robert J Baatenburg de Jong; Leendert H J Looijenga; Senada Koljenović; Jose A Hardillo Journal: Cancers (Basel) Date: 2022-03-15 Impact factor: 6.639