title: Absent and abundant MET immunoreactivity is associated with poor prognosis of patients with oral and oropharyngeal squamous cell carcinoma.
abstract: 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.
authors.affiliation: Department of Othorhinolaryngology and Head and Neck Surgery, Erasmus MC, University Medical Center Rotterdam, Rotterdam, The Netherlands.
authors.forename: Maria J
authors.initials: MJ
authors.lastname: De Herdt
authors.affiliation: Department of Pathology, University Medical Center Utrecht, Utrecht, The Netherlands.
authors.forename: Stefan M
authors.initials: SM
authors.lastname: Willems
authors.affiliation: Department of Othorhinolaryngology and Head and Neck Surgery, Erasmus MC, University Medical Center Rotterdam, Rotterdam, The Netherlands.
authors.forename: Berdine
authors.initials: B
authors.lastname: van der Steen
authors.affiliation: Department of Pathology, University Medical Center Utrecht, Utrecht, The Netherlands.|Department of Oral and Maxillofacial Surgery, University Medical Center Utrecht, Utrecht, The Netherlands.
authors.forename: Rob
authors.initials: R
authors.lastname: Noorlag
authors.affiliation: Department of Pathology, Erasmus MC, University Medical Center Rotterdam, Rotterdam, The Netherlands.
authors.forename: Esther I
authors.initials: EI
authors.lastname: Verhoef
authors.affiliation: Department of Pathology, Erasmus MC, University Medical Center Rotterdam, Rotterdam, The Netherlands.
authors.forename: Geert J L H
authors.initials: GJ
authors.lastname: van Leenders
authors.affiliation: Department of Oral and Maxillofacial Surgery, University Medical Center Utrecht, Utrecht, The Netherlands.
authors.forename: Robert J J
authors.initials: RJ
authors.lastname: van Es
authors.affiliation: Department of Pathology, Erasmus MC, University Medical Center Rotterdam, Rotterdam, The Netherlands.
authors.forename: Senada
authors.initials: S
authors.lastname: KoljenoviÄ
authors.affiliation: Department of Othorhinolaryngology and Head and Neck Surgery, Erasmus MC, University Medical Center Rotterdam, Rotterdam, The Netherlands.
authors.forename: Robert J
authors.initials: RJ
authors.lastname: Baatenburg de Jong
authors.affiliation: Department of Pathology, Erasmus MC, University Medical Center Rotterdam, Rotterdam, The Netherlands.
authors.forename: Leendert H J
authors.initials: LH
authors.lastname: Looijenga
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000911:Antibodies, Monoclonal; D000918:Antibody Specificity; D014408:Biomarkers, Tumor / Q000032:analysis*; D002294:Carcinoma, Squamous Cell / Q000378:metabolism / Q000401:mortality / Q000473:pathology*; D018572:Disease-Free Survival; D005260:Female; D006258:Head and Neck Neoplasms / Q000378:metabolism / Q000401:mortality / Q000473:pathology*; D006801:Humans; D007150:Immunohistochemistry / Q000379:methods*; D053208:Kaplan-Meier Estimate; D008297:Male; D008875:Middle Aged; D009062:Mouth Neoplasms / Q000378:metabolism / Q000401:mortality / Q000473:pathology*; D009959:Oropharyngeal Neoplasms / Q000378:metabolism / Q000401:mortality / Q000473:pathology*; D011379:Prognosis; D019859:Proto-Oncogene Proteins c-met / Q000032:analysis* / Q000096:biosynthesis; D015203:Reproducibility of Results; D000077195:Squamous Cell Carcinoma of Head and Neck
chemical_list: D000911:Antibodies, Monoclonal; D014408:Biomarkers, Tumor; D019859:Proto-Oncogene Proteins c-met
keywords: C-terminal MET; antibody validation; immunohistochemistry; oral and oropharyngeal squamous cell carcinoma; prognosis