Abstract 720: Identification of novel molecular markers for detecting lymph node metastasis of oral squamous cell carcinoma

Abstract

Abstract Cervical lymph node metastasis is a potent prognostic factor in oral squamous cell carcinoma (OSCC). Management of occult metastasis is an important issue for the surgeons. Sentinel lymph node biopsy (SLNB) is highlighted for its role in deciding making of neck dissection. We have performed the SLNB for cN0 cases routinely and reported the clinical usefulness. Accurate diagnosis of the metastasis in sentinel lymph nodes is important but depends on a heavy workload of the pathologist. We carried out a clinical study to evaluate a novel automated assay system for cytokeratin 19 (CK19) mRNA, the one-step nucleic acid amplification (OSNA) method, to detect the lymph node metastasis of OSCC. The accuracy of OSNA assay was nearly 95%, but it could not detect occult metastasis in case of no or low expression of CK19 mRNA in the primary tumor. In this study, we attempted to identify novel molecular markers to find the harboring cancer cells in the lymph node. First, we determined the gene expression profiles in 7 metastatic lymph nodes from patients with OSCC, 1 benign lymph node, and 5 salivary gland tissues from non-cancerous patients by microarray analysis. We found the overexpression of 36 genes in all metastatic lymph nodes but not in benign lymph node and salivary glands. Subsequently, we examined the expression of these genes in newly 15 metastatic lymph nodes and 9 benign lymph nodes by real-time quantitative RT-PCR method. Among the 36 genes, the expression of annexin A8-like 2 (ANXA8L2) and desmoglein 3 (DSG3) was commonly detected in metastatic lymph nodes at much higher level but not in benign lymph nodes at all. Furthermore, we retrospectively evaluated the usefulness of these markers with the use of 330 lymph nodes that were histopathologically metastasis-positive in 62 and metastasis-negative in 268. The accuracy of each marker CK19, ANXA8L2 and DSG3 is all near 90%. However, the combination of these markers improved the sensitivity up to 96-100%. Expression of ANXA8L2 and DSG3 was also detected in approximately 3% of the histopathologically metastasis-negative lymph nodes. These results suggested that ANXA8L2 and DSG3 could be useful molecular markers and improve detection rate of occult metastasis. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 103rd Annual Meeting of the American Association for Cancer Research; 2012 Mar 31-Apr 4; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2012;72(8 Suppl):Abstract nr 720. doi:1538-7445.AM2012-720