Koos Boeve

113 Cyclin D1 in early oral cancer or extracapsular spread in the metastasis. A logistic regression model revealed cyclin D1 expression as a most robust predictor for occult nodal metastasis (p = 0.005), together with noncohesive tumor front (p = 0.015) and perineural growth (p = 0.033). Validation of cyclin D1 on independent cohort Baseline characteristics of the independent multicenter cohort of 155 early tongue and FOM carcinomas, are given in Table 1. Cyclin D1 expression could be scored in 147 tumors (95%). The interobserver agreement between both observers (S.M.W. and K.B.), blinded for each other scores, had an ICC of 0.94. In the whole cohort cyclin D1 expression was significantly correlated with occult nodal metastasis (p = 0.033). When tumor sites were analyzed separately, cyclin D1 correlated only with occult nodal metastasis in early FOM oral cavity SCC, with a NPV of 79% (p = 0.020; Table 5). Table 5. Correlation of cyclin D1 by IHC with occult nodal metastasis in validation cohort pN0 (90 tumors) pN+ (47 tumors) p-value Whole cohort of OSCC Normal cyclin D1 expression Cyclin D1 overexpression 55 (76%) 45 (60%) 17 (24%) 30 (40%) 0.033 Tongue Normal cyclin D1 expression Cyclin D1 overexpression 29 (74%) 28 (67%) 10 (26%) 14 (33%) 0.449 FOM Normal cyclin D1 expression Cyclin D1 overexpression 26 (79%) 17 (51%) 7 (21%) 16 (49%) 0.020 Abbreviations : IHC, immunohistochemistry; OSCC, oral squamous cell carcinoma; FOM, floor of mouth; pN, histological N-classification based on elective neck dissection. In bold: the negative predictive value (NPV) in early OSCC. DISCUSSION Adequate determination of the nodal status is pivotal for appropriate treatment planning in early oral cavity SCC. Unfortunately, even optimal imaging with CT or MRI, PET-CT and ultrasound with FNAC lacks high sensitivity for the detection of nodal metastasis. As a result, an elective neck dissection or SNB still are the preferred staging techniques of the neck in clinically early oral cavity SCC (cT1-2cN0) [1]. However, this policy leads to an overtreatment of the neck in 60% to 70% of the patients, which urges the need for predictive biomarkers in early oral cancer [2]. In earlier research, copy number gain in region 11q13 was identified as a potential biomarker in early oral cancer with a NPV of 79% [13]. A review with meta- analysis revealed a correlation with nodal metastasis in oral cavity SCC of both amplification