Distinctive E-Cadherin and Epidermal Growth Factor Receptor Expression in Metastatic and Nonmetastatic Head and Neck Squamous Cell Carcinoma: Predictive and Prognostic Correlation.
Muller, Susan DMD 1; Su, Ling PhD 2; Tighiouart, Mourad PhD 3; Saba, Nabil MD 2; Zhang, Hongzheng PhD 2; Shin, Dong M. MD 2; Chen, Zhuo (Georgia) PhD 2*,+
[Miscellaneous Article]
Cancer.
113(1):97-107, July 1, 2008.
(Format: HTML, PDF)
BACKGROUND. The authors investigated whether coexpression and localization of E-cadherin (E-cad) and epidermal growth factor receptor (EGFR) had predictive and/or prognostic correlations with lymph node metastasis and/or survival in patients with squamous cell carcinoma of the head and neck (SCCHN).
METHODS. Immunohistochemistry (IHC) of archival tissue was performed to measure expression of EGFR and E-cad in surgical specimens of SCCHN (n = 143) that included primary tumors (PTs) with positive lymph nodes (Tu Met) and their paired lymph node metastases (LnMet), PTs with negative lymph nodes (Tu-Met), and benign tissue biopsies as normal controls. IHC staining was quantified as a weighted index and as the ratio of membrane to cytoplasmic staining. Correlative expression between EGFR and E-cad also was examined in SCCHN cell lines by immunoblotting and immunofluorescence analyses.
RESULTS. Three distinct expression patterns of EGFR and E-cad were observed. Membrane localization of E-cad was significantly lower in the Tu Met group than in the Tu-Met group (P = .01) and was associated inversely with lymph node status (P = .009). Wilcoxon analysis of the combined markers demonstrated that expression and/or membrane localization of EGFR and E-cad were correlated with disease-free survival and overall survival in patients with SCCHN. The study of SCCHN cell lines demonstrated that cells with positive but low EGFR expression and with negative E-cad expression were relatively resistant to the EGFR tyrosine kinase inhibitor erlotinib.
CONCLUSIONS. The current study suggested that examining not only the expression but also the localization of EGFR and E-cad simultaneously may have clinical relevance in predicting lymph node metastasis, patient survival, and response to EGFR-targeted therapy in patients with SCCHN. Cancer 2008. (C) 2008 American Cancer Society.
Copyright (C) 2008 John Wiley & Sons, Inc.