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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

Purpose: 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 and Materials: 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)more » 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.« less

Authors:
 [1];  [2]; ; ;  [1];  [3];  [3]
  1. Department of Radiation Oncology, William Beaumont Hospital, Royal Oak, Michigan (United States)
  2. Department of Pathology, William Beaumont Hospital, Royal Oak, Michigan (United States)
  3. Beaumont BioBank, William Beaumont Hospital, Royal Oak, Michigan (United States)
Publication Date:
OSTI Identifier:
22416475
Resource Type:
Journal Article
Journal Name:
International Journal of Radiation Oncology, Biology and Physics
Additional Journal Information:
Journal Volume: 88; Journal Issue: 3; Other Information: Copyright (c) 2014 Elsevier Science B.V., Amsterdam, The Netherlands, All rights reserved.; Country of input: International Atomic Energy Agency (IAEA); Journal ID: ISSN 0360-3016
Country of Publication:
United States
Language:
English
Subject:
62 RADIOLOGY AND NUCLEAR MEDICINE; CARCINOMAS; CHEMOTHERAPY; COMBINED THERAPY; GROWTH FACTORS; HAZARDS; HEAD; METASTASES; MULTIVARIATE ANALYSIS; NECK; PATIENTS; RADIOTHERAPY; RECEPTORS

Citation Formats

Baschnagel, Andrew M., Williams, Lindsay, Hanna, Alaa, Chen, Peter Y., Krauss, Daniel J., Pruetz, Barbara L., Akervall, Jan, Department of Otolaryngology, William Beaumont Hospital, Royal Oak, Michigan, Wilson, George D., E-mail: George.Wilson@Beaumont.edu, and Beaumont BioBank, William Beaumont Hospital, Royal Oak, Michigan. c-Met Expression Is a Marker of Poor Prognosis in Patients With Locally Advanced Head and Neck Squamous Cell Carcinoma Treated With Chemoradiation. United States: N. p., 2014. Web. doi:10.1016/J.IJROBP.2013.11.013.
Baschnagel, Andrew M., Williams, Lindsay, Hanna, Alaa, Chen, Peter Y., Krauss, Daniel J., Pruetz, Barbara L., Akervall, Jan, Department of Otolaryngology, William Beaumont Hospital, Royal Oak, Michigan, Wilson, George D., E-mail: George.Wilson@Beaumont.edu, & Beaumont BioBank, William Beaumont Hospital, Royal Oak, Michigan. c-Met Expression Is a Marker of Poor Prognosis in Patients With Locally Advanced Head and Neck Squamous Cell Carcinoma Treated With Chemoradiation. United States. https://doi.org/10.1016/J.IJROBP.2013.11.013
Baschnagel, Andrew M., Williams, Lindsay, Hanna, Alaa, Chen, Peter Y., Krauss, Daniel J., Pruetz, Barbara L., Akervall, Jan, Department of Otolaryngology, William Beaumont Hospital, Royal Oak, Michigan, Wilson, George D., E-mail: George.Wilson@Beaumont.edu, and Beaumont BioBank, William Beaumont Hospital, Royal Oak, Michigan. 2014. "c-Met Expression Is a Marker of Poor Prognosis in Patients With Locally Advanced Head and Neck Squamous Cell Carcinoma Treated With Chemoradiation". United States. https://doi.org/10.1016/J.IJROBP.2013.11.013.
@article{osti_22416475,
title = {c-Met Expression Is a Marker of Poor Prognosis in Patients With Locally Advanced Head and Neck Squamous Cell Carcinoma Treated With Chemoradiation},
author = {Baschnagel, Andrew M. and Williams, Lindsay and Hanna, Alaa and Chen, Peter Y. and Krauss, Daniel J. and Pruetz, Barbara L. and Akervall, Jan and Department of Otolaryngology, William Beaumont Hospital, Royal Oak, Michigan and Wilson, George D., E-mail: George.Wilson@Beaumont.edu and Beaumont BioBank, William Beaumont Hospital, Royal Oak, Michigan},
abstractNote = {Purpose: 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 and Materials: 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.},
doi = {10.1016/J.IJROBP.2013.11.013},
url = {https://www.osti.gov/biblio/22416475}, journal = {International Journal of Radiation Oncology, Biology and Physics},
issn = {0360-3016},
number = 3,
volume = 88,
place = {United States},
year = {Sat Mar 01 00:00:00 EST 2014},
month = {Sat Mar 01 00:00:00 EST 2014}
}