Correlation of expression and localization of E-cadherin and EGFR in metastatic and non-metastatic head and neck cancer Free

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Reliable detection of lymph node metastases (LNM) in squamous cell carcinoma of the head and neck (SCCHN) is paramount for appropriate treatment. Therefore, using biomarkers to assist in accurate detection of LNM may help to improve treatment of SCCHN. E-cadherin (E-cad) and epidermal growth factor receptor (EGFR) are important in progression of SCCHN. Loss of E-cad is correlated to epithelial-mesenchymal transition (EMT) which is essential for metastasis. Several reports have recently illustrated that loss of E-cad is responsible for resistance to EGFR targeted therapy. The current study investigates whether correlation of EGFR and E-cad expression has more clinical implication in LNM of SCCHN than either one as a single marker. Immunohistochemistry (IHC) staining was performed to detect the expression of EGFR and E-cad in paraffin-embedded surgical specimens from SCCHN patients. The samples consist of three groups: primary tumors with positive lymph nodes (Tu-1, n=49), paired lymph node metastases (Met-1, n=47), and primary tumors with negative lymph nodes (Tu-2, n=47). The IHC staining was quantified as Weighted Index (WI = % positively tumor area x intensity of the staining as 1+ to 3+). The ratio of membrane to cytoplasmic staining (RMC) was also recorded. We found three major patterns of E-cad and EGFR expression: EGFR (+)/E-cad (+), EGFR (+)/E-cad (-), and EGFR (-)/E-cad (-). In the first case, EGFR and E-cad were both expressed mainly in the cell membrane of well-differentiated (WD) and in some moderately-differentiated (MD) tumors. In the case of EGFR (+)/E-cad (-), EGFR showed strong membrane staining, but E-cad showed weak or no cytoplasmic staining in poorly-differentiated (PD) and in some MD tumors. In the third case, both E-cad and EGFR showed weak or no cytoplasmic staining mainly in PD tumors. Two-sample t-test showed that both WI and RMC of E-cad were lower in the Tu-1 group than those in the Tu-2 group (p = 0.059 and 0.01, respectively). Paired t-test comparison between the Tu-1 and the Met-1 illustrated that WIs of both EGFR and E-cad as well as RMC of EGFR were lower in the Met-1 than those in the Tu-1 groups (p = 0.013, 0.009, and 0.038, respectively). Spearman correlation demonstrated that RMCs of EGFR and E-cad were correlated in both Tu-1 and Tu-2 groups (p < 0.001 and p = 0.005, respectively). RMC of EGFR and WI of E-cad were correlated in the node positive group (Tu-1, p < 0.001). Log-Rank statistical analysis showed that combining RMC of EGFR and WI of E-cad correlated to disease-free survival in both Tu-1 and Tu-2 groups (p = 0.022 and p = 0.027, respectively). Our study suggests that expression of E-cad and EGFR are associated with their localization in SCCHN. Examining the both biomarkers simultaneously may facilitate accurate prediction of LNM and the survival of patients with SCCHN. (Supported by NIH grant R21 DE014767 to ZGC and GCC Distinguished Cancer Scholar to DMS).