Head and neck squamous cell carcinoma (HNSCC) is the fifth most common malignancy worldwide. In 1999, in the US, approximately 29'800 patients suffered from a squamous cell carcinoma of the oropharynx and the oral cavity and more than 8000 died of it . Despite improvements in surgical treatment and radiation technology over the last decades, prognosis remains dismal in advanced cases. Regional metastatic disease is known to reduce recurrence free survival and disease specific survival significantly .
A chief feature of malignant behavior is the capability of tumour cells to metastasize. Metastatic spread is an extremely bad prognostic factor and responsible for cause of death in ~90% of all cancer patients . The cellular mechanisms responsible for the acquisition of a metastatic phenotype include the adaptation to potential hostile environment (blood stream, lymph nodes, organ of metastasis). In addition, the "tumour cell-to-tumour cell" and "tumour cell-to-stromal environment" cross talk is recognized as an important condition for invasion and metastasis.
Sentinel node biopsy (SNB) for the cN0 neck in early HNSCC of the oral cavity has been validated by multiple studies. The workup of sentinel lymph nodes is performed as described elsewhere  and reliably detects occult metastatic disease. Further, occult metastatic disease is subdivided in macrometastasis (>2 mm), micrometastasis (0.2-2 mm) and even small tumour cells or small clusters <0.2 mm (isolated tumour cells, ITC).
The hitherto published predictive factors for metastatic disease in early HN tumours are histomorphological parameters like mode of invasion (MOI; morphological appearance of the infiltrating tumour front), depth of tumour infiltration, grade of differentiation (GOD), lymphatic invasion (LI)  and intratumoural lymphatic density .
The ECAD glycoprotein (encoded by the CDH1 gene, located on chromosome 16q22.1) is a Ca2+-dependent intercellular adhesion molecule in epithelial cells, which plays an important role in establishing and maintaining intercellular connections and morphogenesis. The cytoplasmatic terminus of the ECAD molecule has been shown to be linked to the actin cytoskeleton via α-catenin and β-catenin .
Dysfunction of ECAD/catenin complex is directly involved in carcinogenesis. CDH1 is considered to be a tumour suppressor gene, whose loss has also been demonstrated to promote tumour invasion and metastasis in various cancer models . There are several mechanisms for abnormal ECAD expression in cancer, including allelic loss at the CDH1 locus as well as somatic and, rarely, germ line mutations. Transcriptional repression of ECAD by promoter hypermethylation has also been reported in several tumour types and cell lines and reduced expression of ECAD in esophageal Adenocarcinoma was shown to correlate with poor prognosis [9, 10].
Changes or alterations in the function and expression of this cell to cell adhesion molecule have been postulated to be an early event in the multiple step process of tumour metastasis and an important factor in tumour progression .
It is reported that down regulation of α-catenin and β-catenin seems to be associated with dysfunction of ECAD mediated cell adhesion and an increase in the metastatic potential of cancer cells .
The correlation between the expression of the ECAD-associated molecules and the presence of neck metastasis is significant, indicating that reduced expression of ECAD is a key function in the increased incidence of neck metastasis .
In this study, we aimed to determine the potential of ECAD expression in predicting early metastatic disease of patients with HNSCC of the oral cavity and oropharynx by analyzing a very well defined patient cohort (T1,T2 oral cavity and oropharyngeal cancers) with meticulous workup of sentinel lymph nodes.
The hypothesis was that low expression of ECAD leads to reduced tumour cell to tumour cell adhesion and therefore easier disintegration of single tumour cells with increased risk of occult metastatic disease in analogy to the results published by Hirata et al. for small cell lung cancer .