Koos Boeve

125 Molecular biomarkers in SLNB staged early oral cancer INTRODUCTION A positive lymph node status (N-status) is one of the most important prognostic factors for shorter disease specific and disease-free survival in oral squamous cell carcinoma (OSCC) [1]. In OSCC, metastatic cells will drain to regional lymph nodes located in cervical neck levels [2]. Despite a clinically negative neck, early stage OSCC (cT1-2N0) patients have a reported 23% to 37% risk for occult (preoperatively undetected) lymph node metastasis [3-5]. The sentinel lymph node biopsy (SLNB) has been introduced in the last decade as diagnostic technique for the detection of occult metastasis, in order to select early stage OSCC patients for a neck dissection or a clinical follow-up strategy [1]. In the Netherlands, patients with a metastasis-positive sentinel lymph node (SLN) currently receive a modified radical neck dissection (MRND) in a second surgical procedure [6,7]. A meta-analysis reported a high pooled sensitivity (87%) and negative predictive value (94%) for detecting occult metastasis using the SLNB procedure [8]. Advantages of the SLNB are individual drainage pattern assessment [9] and more detailed lymph node information with the possibility to detect micrometastasis (0.2-2 mm) and isolated tumor cells (ITCs, metastasis size <0.2 mm) [7]. Despite these advantages, the SLNB is still an invasive staging procedure. Preoperative selection of patients at risk for occult metastasis using molecular tumor profiling might lead to a more individualized neck strategy with a watchful waiting strategy for low risk patients [10], a SLNB for intermediate risk patients and a neck dissection for patients with a high risk [11]. The additional and more detailed information on individual drainage patterns, micrometastasis and ITCs provided by the SLNB might have impact on the clinical value of molecular biomarkers that have previously been associated with N-status [12]. Currently, only few studies reported the value of clinico-pathological markers to predict N-status in a cohort of early stage OSCC patients who underwent neck staging using the SLNB procedure [12-14] with clinical follow-up as reference for the SLNB negative patients. Only one study validated the clinical value of CD44 as a molecular tumor biomarker, but did not find an association with N-status [11]. Before the introduction of the SLNB procedure, patients with a pT1cN0 tumor and a tumor infiltration depth <4 mmwere selected for a watchful waiting strategy instead of an elective neck dissection [15]. Tumor profiling using molecular biomarkers to predict N-status in OSCC has been studied before. One such a well-studied genetic alteration in head and neck squamous cell carcinomas that has been associated with N-status is amplification of chromosome 11q13 [16-19]. Three genes ( CTTN, CCND1 and FADD ) located in this commonly amplified region have previously been validated for N-status in a well-defined early stage OSCC cohort with neck staging by END. A negative predictive value (NPV) of 80-84% was