title: Alteration status and prognostic value of MET in head and neck squamous cell carcinoma.
abstract: The MET pathway plays a key role in various cancers, and its inhibition represents a potential treatment target. However, appropriate biomarkers are needed to facilitate the selection of patients who would benefit from MET inhibiting therapy. We herein conducted a robust confirmatory evaluation of theMETcopy number alteration status and prognostic significance of c-Met expression in a large series of patients (n = 396) who underwent standard surgical resection and adjuvant chemoradiotherapy for head and neck squamous cell carcinoma (HNSCC). Surgically resected HNSCC samples were subjected to immunohistochemical and H-score analysis of c-Met expression and silver in situ hybridization analysis ofMETamplification and copy number gains. c-Met expression varied, with mean and median H-scores (scale: 0-300 scale) of 61.2 and 60.0, respectively. The lowest and highest expression levels were observed in SCC of the larynx and oral cavity, respectively.METcopy number gains were observed in 16.9% of cases (67/339) and were associated with c-Met protein expression. High c-Met expression, determined according toMETgain status, was associated with an inferior overall survival rate, especially among completely resected cases. In conclusion, our robust analysis revealed that c-Met expression in HNSCCs varied according to anatomical site, correlated withMETcopy number gains, and was associated with poor prognosis. This c-Met expression analysis method, which is based on theMETgain status, appears to appropriately predict high-risk HNSCC patients in the context of anti-MET therapeutic decisions.
authors.affiliation: Department of Pathology, Yonsei University College of Medicine, Seoul, Korea.
authors.forename: Yoon Ah
authors.initials: YA
authors.lastname: Cho
authors.affiliation: Department of Pathology, Yonsei University College of Medicine, Seoul, Korea.
authors.forename: Eun Kyung
authors.initials: EK
authors.lastname: Kim
authors.affiliation: Yonsei Cancer Center, Division of Medical Oncology, Yonsei University College of Medicine, Seoul, Korea.
authors.forename: Su Jin
authors.initials: SJ
authors.lastname: Heo
authors.affiliation: Yonsei Cancer Center, Division of Medical Oncology, Yonsei University College of Medicine, Seoul, Korea.
authors.forename: Byoung Chul
authors.initials: BC
authors.lastname: Cho
authors.affiliation: Yonsei Cancer Center, Division of Medical Oncology, Yonsei University College of Medicine, Seoul, Korea.
authors.forename: Hye Ryun
authors.initials: HR
authors.lastname: Kim
authors.affiliation: Yonsei University College of Medicine, Seoul, Korea.
authors.forename: Ji Myung
authors.initials: JM
authors.lastname: Chung
authors.affiliation: Department of Pathology, Yonsei University College of Medicine, Seoul, Korea.
authors.forename: Sun Och
authors.initials: SO
authors.lastname: Yoon
keywords: Head and neck squamous cell carcinoma; MET gene; Prognosis; c-Met protein