Koos Boeve

25 General introduction and scope of this thesis Previously an association was observed between lymph node metastasis and disease specific survival and between lymph node metastasis and the expression of cortactin, cyclin D1, and FADD, three genes located in the chromosome 11q13 region and amplified in 13 to 29% of the HNSCC [47,55]. In chapter 6, both 11q13 chromosome amplification and expression of cortactin, cyclin D1 and FADD were associated with occult metastasis using a large multicentre cohort of 313 early stage OSCC patients collected from the databases of UMCU and UMCG. Although the SLNB procedure is minor surgery compared to an END, it is still an invasive procedure in ~75% of the early stage OSCC patients who eventually had no lymph node involvement. In chapter 7 molecular tumour biomarkers (cortactin, cyclin D1, FADD, RAB25, S100A9) previously reported as associated with lymph node status in OSCC, were analysed for their clinical value to select patients with a low risk for lymph node metastasis for a watchful waiting instead of a SLNB procedure. All included early stage OSCC patients had neck staging using the SLNB procedure which provide detailed lymph node involvement information. Expression levels of the selected molecular markers were associated with lymph node status using tissue micro arrays constructed from tumour biopsy and tumour resection tissues. In chapter 8 we describe the selection of new OSCC-specific methylation markers using an OSCC-methylome based on genome wide methylation screening approach. Selected methylation markers were validated in a feasibility study with saliva of ten OSCC patients and ten healthy controls using a quantitative methylation specific PCR (QMSP).