Down regulation of E-Cadherin (ECAD) - a predictor for occult metastatic disease in sentinel node biopsy of early squamous cell carcinomas of the oral cavity and oropharynx

Abstract

BackgroundPrognostic factors in predicting occult lymph node metastasis in patients with head and neck squamous-cell carcinoma (HNSCC) are necessary to improve the results of the sentinel lymph node procedure in this tumour type. The E-Cadherin glycoprotein is an intercellular adhesion molecule in epithelial cells, which plays an important role in establishing and maintaining intercellular connections.ObjectivesTo determine the value of the molecular marker E-Cadherin in predicting regional metastatic disease.MethodsE-Cadherin expression in tumour tissue of 120 patients with HNSCC of the oral cavity and oropharynx were evaluated using the tissue microarray technique. 110 tumours were located in the oral cavity (91.7%; mostly tongue), 10 tumours in the oropharynx (8.3%). Intensity of E-Cadherin expression was quantified by the Intensity Reactivity Score (IRS). These results were correlated with the lymph node status of biopsied sentinel lymph nodes. Univariate and multivariate analysis was used to determine statistical significance.ResultspT-stage, gender, tumour side and location did not correlate with lymph node metastasis. Differentiation grade (p = 0.018) and down regulation of E-Cadherin expression significantly correlate with positive lymph node status (p = 0.005) in univariate and multivariate analysis.ConclusionThese data suggest that loss of E-cadherin expression is associated with increased lymhogeneous metastasis of HNSCC. E-cadherin immunohistochemistry may be used as a predictor for lymph node metastasis in squamous cell carcinoma of the oral cavity and oropharynx.Level of evidence: 2b

High sex determining region Y-box 2 expression is a negative predictor of occult lymph node metastasis in early squamous cell carcinomas of the oral cavity

“…Therefore, additional biomarkers may be of help for better patient stratification to select for SNB or elective neck dissection. In a previous study, we demonstrated that expression of E-Cadherin (ECAD) 19 significantly correlated with occult metastatic disease. In the future, a combination of molecular Table 3 Logistic regression: Adjusted odds ratios (ORs), 95% confidence intervals (95% CIs) and p-value of SOX2 expression and tumour stage as predictors for lymph node status.…”

“…18,19 In brief, 133 patients of the ear nose and throat departments of the University Hospital of Zurich and the Kantonsspital St. Gallen, Switzerland, with early stage (T1/T2) SCC of the oral cavity and the tonsillar pillar without preoperative clinical and imaging evidence of regional lymph node metastasis were selected for this study. SCCs of the tonsillar pillar were included, because they behave similarly to oral cavity carcinoma rather than Human Papilloma Virus (HPV)-positive tonsillar carcinoma.…”

Curcumin Inhibits Invasiveness and Epithelial-Mesenchymal Transition in Oral Squamous Cell Carcinoma Through Reducing Matrix Metalloproteinase 2, 9 and Modulating p53-E-Cadherin Pathway

“…11 Several studies have identified that reduced E-cadherin expression is associated with short overall survival in many epithelial tumors. [12][13][14][15][16] Our previous study has shown that Snail and Twist are upregulated and E-cadherin is downregulated specifically in OSCC patients. Lower E-cadherin expression is an independent prognostic marker of OSCC patients.…”

Prognostic implications of node metastatic features in OSCC: A retrospective study on 121 neck dissections

“…pN+ was found in 2 out of 42 NDs performed after SLN+ (0/11, 0%, pN+ in cT1-cN0M0 NDs and 2/31, 6.45%, in cT2-cN0M0 NDs), thus confuting previous literature supporting its role as a diagnostic marker for other nodal metastases (24,25) and bringing the predictive role of SLN positivity into discussion, leading us to conclude that a ND secondary to SLN+ is an overtreatment in 100% of cT1-cN0M0 NDs and in 93.55% of cT2-cN0M0 NDs. We suggest conducting further biomolecular studies focusing on molecular markers able to predict occult metastatic disease in SLN biopsies, thereby improving the quality of the treatments (26).…”