title: Combined CD44, c-MET, and EGFR expression in p16-positive and p16-negative head and neck squamous cell carcinomas.
abstract: OBJECTIVE
  To examine the association between CD44 and c-MET expression in relation to p16 and EGFR in patients with head and neck squamous cell carcinoma (HNSCC).
  
  
  METHODS
  Immunohistochemical staining of CD44, p16, EGFR, and c-MET was performed on 105 locally advanced HNSCC patients treated with chemoradiation. CD44 expression was correlated with c-MET, EGFR, and p16, locoregional control (LRC), distant metastases (DM), disease-free survival (DFS) and overall survival (OS).
  
  
  RESULTS
  High CD44 expression was present in 33% of patients and was associated with non-oropharynx primaries (P < 0.001), high c-MET expression (P < 0.001), p16-negative (P < 0.001) and EGFR-positive tumors (P < 0.001). Fifty-seven percent of CD44 high expressing tumors had high c-MET expression compared to 21% of CD44 low expressing tumors (P < 0.001). High CD44 expression predicted for worse LRC (HR: 2.44; 95% CI: 1.16-5.13; P = 0.018), DFS (HR: 2.61; 95% CI: 1.46-4.67; P = 0.001), and OS (HR: 2.52; 95% CI: 1.30-4.92; P = 0.007) but not DM (P = 0.57) on univariate analysis. Patients with both high CD44 and c-MET expression had a poor prognosis with a 2-year DFS of 30% compared to 70% in the rest of the cohort (P = 0.003). On multivariable analysis, after adjusting for site, T-stage, smoking history, and EGFR status, high c-MET (P = 0.039) and negative p16 status (P = 0.034) predicted for worse DFS, while high CD44 expression did not (P = 0.43).
  
  
  CONCLUSIONS
  High CD44 expression is associated with high c-MET expression, p16-negative tumors, and EGFR-positive tumors. The combination of these markers predicts for poor prognosis in HNSCC patients treated with chemoradiation.
authors.affiliation: Department of Human Oncology, University of Wisconsin Carbone Cancer Center, School of Medicine and Public Health, University of Wisconsin, Madison, WI, USA.
authors.forename: Andrew M
authors.initials: AM
authors.lastname: Baschnagel
authors.affiliation: Department of Radiation Oncology, William Beaumont Hospital, Royal Oak, MI, USA.
authors.forename: Nathan
authors.initials: N
authors.lastname: Tonlaar
authors.affiliation: Department of Pathology, William Beaumont Hospital, Royal Oak, MI, USA.
authors.forename: Mohammad
authors.initials: M
authors.lastname: Eskandari
authors.affiliation: Department of Pathology, William Beaumont Hospital, Royal Oak, MI, USA.
authors.forename: Tripti
authors.initials: T
authors.lastname: Kumar
authors.affiliation: Department of Pathology, William Beaumont Hospital, Royal Oak, MI, USA.
authors.forename: Lindsay
authors.initials: L
authors.lastname: Williams
authors.affiliation: Department of Radiation Oncology, William Beaumont Hospital, Royal Oak, MI, USA.
authors.forename: Alaa
authors.initials: A
authors.lastname: Hanna
authors.affiliation: Beaumont BioBank, William Beaumont Hospital, Royal Oak, MI, USA.
authors.forename: Barbara L
authors.initials: BL
authors.lastname: Pruetz
authors.affiliation: Department of Radiation Oncology, William Beaumont Hospital, Royal Oak, MI, USA.|Beaumont BioBank, William Beaumont Hospital, Royal Oak, MI, USA.
authors.forename: George D
authors.initials: GD
authors.lastname: Wilson
mesh_terms: D002294:Carcinoma, Squamous Cell / Q000378:metabolism* / Q000473:pathology / Q000821:virology; D066246:ErbB Receptors / Q000378:metabolism*; D006258:Head and Neck Neoplasms / Q000378:metabolism* / Q000473:pathology / Q000821:virology; D052162:Human papillomavirus 16 / Q000302:isolation & purification; D006801:Humans; D018960:Hyaluronan Receptors / Q000378:metabolism*; D053208:Kaplan-Meier Estimate; D015999:Multivariate Analysis; D030361:Papillomavirus Infections / Q000150:complications; D011379:Prognosis; D019859:Proto-Oncogene Proteins c-met / Q000378:metabolism*; D000077195:Squamous Cell Carcinoma of Head and Neck
chemical_list: C497483:CD44 protein, human; D018960:Hyaluronan Receptors; D066246:ErbB Receptors; C491743:MET protein, human; D019859:Proto-Oncogene Proteins c-met
keywords: 
  EGFR
  ; CD44; HNSCC; HPV; biomarkers; c-MET