title: c-Met expression is a marker of poor prognosis in patients with locally advanced head and neck squamous cell carcinoma treated with chemoradiation.
abstract: OBJECTIVE
  To examine the prognostic significance of c-Met expression in relation to p16 and epidermal growth factor receptor (EGFR) in patients with locally advanced head and neck squamous cell carcinoma (HNSCC) treated with definitive concurrent chemoradiation.
  
  
  METHODS
  Archival tissue from 107 HNSCC patients treated with chemoradiation was retrieved, and a tissue microarray was assembled. Immunohistochemical staining of c-Met, p16, and EGFR was performed. c-Met expression was correlated with p16, EGFR, clinical characteristics, and clinical endpoints including locoregional control (LRC), distant metastasis (DM), disease-free survival (DFS), and overall survival (OS).
  
  
  RESULTS
  Fifty-one percent of patients were positive for p16, and 53% were positive for EGFR. Both p16-negative (P≤.001) and EGFR-positive (P=.019) status predicted for worse DFS. Ninety-three percent of patients stained positive for c-Met. Patients were divided into low (0, 1, or 2+ intensity) or high (3+ intensity) c-Met expression. On univariate analysis, high c-Met expression predicted for worse LRC (hazard ratio [HR] 2.27; 95% CI, 1.08-4.77; P=.031), DM (HR 4.41; 95% CI, 1.56-12.45; P=.005), DFS (HR 3.00; 95% CI, 1.68-5.38; P<.001), and OS (HR 4.35; 95% CI, 2.13-8.88; P<.001). On multivariate analysis, after adjustment for site, T stage, smoking history, and EGFR status, only high c-Met expression (P=.011) and negative p16 status (P=.003) predicted for worse DFS. High c-Met expression was predictive of worse DFS in both EGFR-positive (P=.032) and -negative (P=.008) patients. In the p16-negative patients, those with high c-Met expression had worse DFS (P=.036) than did those with low c-Met expression. c-Met expression was not associated with any outcome in the p16-positive patients.
  
  
  CONCLUSIONS
  c-Met is expressed in the majority of locally advanced HNSCC cases, and high c-Met expression predicts for worse clinical outcomes. High c-Met expression predicted for worse DFS in p16-negative patients but not in p16-positive patients. c-Met predicted for worse outcome regardless of EGFR status.
authors: Department of Radiation Oncology, William Beaumont Hospital, Royal Oak, Michigan.
authors: Andrew M
authors: AM
authors: Baschnagel
authors: Department of Pathology, William Beaumont Hospital, Royal Oak, Michigan.
authors: Lindsay
authors: L
authors: Williams
authors: Department of Radiation Oncology, William Beaumont Hospital, Royal Oak, Michigan.
authors: Alaa
authors: A
authors: Hanna
authors: Department of Radiation Oncology, William Beaumont Hospital, Royal Oak, Michigan.
authors: Peter Y
authors: PY
authors: Chen
authors: Department of Radiation Oncology, William Beaumont Hospital, Royal Oak, Michigan.
authors: Daniel J
authors: DJ
authors: Krauss
authors: Beaumont BioBank, William Beaumont Hospital, Royal Oak, Michigan.
authors: Barbara L
authors: BL
authors: Pruetz
authors: Beaumont BioBank, William Beaumont Hospital, Royal Oak, Michigan; Department of Otolaryngology, William Beaumont Hospital, Royal Oak, Michigan.
authors: Jan
authors: J
authors: Akervall
authors: Department of Radiation Oncology, William Beaumont Hospital, Royal Oak, Michigan; Beaumont BioBank, William Beaumont Hospital, Royal Oak, Michigan. Electronic address: George.Wilson@Beaumont.edu.
authors: George D
authors: GD
authors: Wilson
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000704:Analysis of Variance; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use; D014408:Biomarkers, Tumor / Q000378:metabolism*; D002294:Carcinoma, Squamous Cell / Q000378:metabolism* / Q000401:mortality / Q000473:pathology / Q000628:therapy*; D059248:Chemoradiotherapy; D019941:Cyclin-Dependent Kinase Inhibitor p16; D018572:Disease-Free Survival; D066246:ErbB Receptors / Q000378:metabolism; D005260:Female; D006258:Head and Neck Neoplasms / Q000378:metabolism* / Q000401:mortality / Q000473:pathology / Q000628:therapy*; D006801:Humans; D008297:Male; D008875:Middle Aged; D009363:Neoplasm Proteins / Q000378:metabolism; D009367:Neoplasm Staging; D011379:Prognosis; D019859:Proto-Oncogene Proteins c-met / Q000378:metabolism*; D000077195:Squamous Cell Carcinoma of Head and Neck; D046888:Tissue Array Analysis / Q000379:methods
chemical_list: D014408:Biomarkers, Tumor; C000614131:CDKN2A protein, human; D019941:Cyclin-Dependent Kinase Inhibitor p16; D009363:Neoplasm Proteins; D066246:ErbB Receptors; D019859:Proto-Oncogene Proteins c-met