Koos Boeve

187 General discussion and future perspectives structures (invadopodia and lamellipodia). Moreover, in vitro studies with squamous cell carcinoma cell lines showed an increase in cell migration with cortactin overexpression [91,93]. A systematic review and meta-analysis from 2019 analysed the clinico-pathological significance of CTTN /cortactin alterations in HNSCC [94]. Nine studies (including chapter 6 ) with a low heterogeneity were included for the association with lymph node status in OSCC. Pooled data of these nine studies resulted in a OR 2.78 (95% CI 1.68-4.60) for positive lymph nodes in patients with CTTN /cortactin alterations. In that meta-analysis, the authors stated that CTTN /cortactin alterations might be helpful to select patients for watchful waiting instead of another neck strategy [94]. However, they recommended further validation of cortactin overexpression with immunohistochemistry (IHC) as preferred approach instead of CTTN amplification detection because its simplicity, low cost and routine automatized application in a pathology setting. Moreover, none of nine included studies used data of patients with neck staging using the SLNB procedure. In line with these studies, in chapter 7 we reported that cortactin overexpression analysed by IHC was associated with SLN status in pT1cN0 OSCCs with a tumour infiltration depth <4 mm. Morand et al. reported that patients might be selected for their neck strategy preoperatively using tumour infiltration depth [95]. They proposed a model for neck staging wherein patients with a tumour infiltration depth <2 mm receive watchful waiting, 2-5 mm a SLNB and >5 mm an END during first surgery. Leusink et al. proposed a model wherein patients are selected for a watchful waiting strategy instead of a SLNB procedure by a molecular tumour profiling using tumour biopsy specimens [96]. In chapter 7 we propose that patients with a pT1 staged tumour and a tumour infiltration depth <4 mm and without cortactin overexpressionmight be selected for a watchful waiting strategy of the neck, while patients with cortactin overexpression or a higher tumour infiltration depth are selected for a SLNB procedure. Larger and prospective studies using tumour biopsy specimens are needed to define and validated the tumour infiltration depth cut-offs for the combination with cortactin. FUTURE PERSPECTIVES Detection of occult metastasis The SLNB procedure is a major step forward in neck staging of early stage OSCC patients compared to the END procedure. However, as long as patients are staged using an invasive procedure and false negatives occur, neck staging needs improvement to reach a more individually successful treatment of early stage patients.