Koos Boeve

103 Cyclin D1 in early oral cancer INTRODUCTION Oral cavity squamous cell carcinomas (SCCs) have the tendency to metastasize to regional lymph nodes in the neck. Determination of the nodal status at the time of diagnosis of the primary tumor is crucial for both prognosis and treatment planning. Even optimal imaging with magnetic resonance imaging (MRI), computed tomography (CT), Positron emission tomography–computed tomography (PET-CT) or ultrasound eventually combinedwith fine needle aspiration cytology (FNAC) has insufficient sensitivity to detect metastatic disease in the neck [1]. This results in a 30% to 40% occult (i.e. clinically and by imaging undetectable) lymph node metastases in early (stage I-II) oral cavity SCC [2]. If the probability of occult cervical metastasis exceeds 20%, literature recommends a selective neck dissection over watchful waiting supported with ultrasound [3,4]. Some clinicians even prefer to decrease this risk below 10%. However, this policy leads to overtreatment of 60% to 70% of the cN0 patients, who are exposed to the potential morbidity of general anesthesia and surgery of the neck such as shoulder dysfunction, paralysis of the lower lip, lymph edema or an altered neck contour [2,5]. There is a need for better diagnostics that are more effective in predicting lymph node metastasis. Two upcoming diagnostic modalities with promising results that overcome this clinical problem are the sentinel node biopsy (SNB) and tumor profiling with biomarkers [1,2]. Although SNB is also an intervention under general anesthesia, it is minor surgery with a lower complication rate as compared to a selective neck dissection [6]. The advantage of tumor profiling on preoperative biopsies over the use of SNB is its non-invasive nature. In 2005, the first gene expression profile to predict nodal metastasis was developed and recently validated in a Dutch multicenter study with a negative predictive value (NPV) of 89% (95% confidence interval 74% to 96%) [2]. This gene expression profile is expensive and its positive predictive value (PPV) was only 37%, which would still result in a substantial amount of unnecessary neck dissections. Therefore, the gene expression profile is not yet the ideal diagnostic modality that could lower overtreatment of the true cN0 neck in early oral cavity SCC [2,7]. Nevertheless, a combination of both tumor profiling and SNB could further improve the diagnostic accuracy of staging the neck [8]. In head and neck squamous cell carcinoma (HNSCC), amplification of the 11q13.3 chromosome region occurs frequently (36%) [9] and has been correlated with aggressive tumor growth, lymph node metastasis, decreased locoregional control and overall survival (OS) [9-12]. In a recent study investigating gene copy number aberrations of 36 common oncogenes and tumor suppressor genes, we identified gain of region 11q13, containing oncogenes CCND1, CTTN, FGF4 and Fass-associated death domain ( FADD ), as a potential predictor for nodal metastasis in early oral cavity SCC, with a NPV of 81% and