Abstract 5287: High accuracy of microRNAs expression in the detection of lymph node metastasis in patients with oral squamous cell carcinomas.

Proceedings: AACR 104th Annual Meeting 2013; Apr 6-10, 2013; Washington, DC The presence of metastatic disease in cervical lymph nodes of oral squamous cell carcinoma (OSCC) patients is one of the most important determinants in therapy choice and prognosis. Thus, the correct staging of regional lymph node metastases is critical to the success of loco-regional control of the disease, response to treatment and thus influences the overall survival of these patients. Routine clinical staging is not always efficient as it might miss occult metastasis and the post-surgical pathologic evaluation of resected lymph nodes through H&E is not sensitive in detecting small metastatic deposits. Thus, there is an urgent need for diagnostic markers and techniques for a rapid and accurate detection of metastatic cells in cervical lymph nodes to guide clinicians in the choice of the most appropriate therapy for these patients. MicroRNAs are promising candidates for diagnostic markers since: (1) they play a role in many pathways involved in tumor metastasis; (2) they are reported to have tumor and tissue-specific expression; (3) their expression is evaluated using the sensitive and rapid qRT-PCR technique; (4) they are suitable to be evaluated in paraffin embedded tissue. Thus, we report here the evaluation of microRNAs as markers in detecting metastatic cells in lymph nodes from OSCC patients. An initial screening using PCR-array compared the expression of 664 microRNAs between metastatic and non-metastatic lymph nodes from 6 OSCC patients and after several inclusion and exclusion criteria, 25 microRNAs were selected as differentially expressed. Four microRNAs were selected for further validation using qRT-PCR in lymph nodes from 48 patients (23 non-metastatic, 18 with macrometastasis, 5 with micrometastasis and 2 with isolated tumor cells). All microRNAs showed 100% specificity. Two microRNAs had high levels of sensitivity (76% and 88%), but were not successful in detecting small metastatic deposits (28.6% and 57.1%). On the other hand, the other two markers were sensitive enough to detect all metastatic samples showing accuracy level, negative and positive predictive values of 100%, as well as AUC values of 1.0. These results show the feasibility of microRNAs as diagnostic markers of cervical metastasis in OSCC patients that can potentially be evaluated using several approaches at different time-points such as pre-treatment diagnostic using fine-needle aspiration biopsies, intraoperative sentinel node biopsy and after surgery as an auxiliary tool to pathology examination, immensely helping in the choice of management of these patients from initial treatment to adjuvant therapy. Citation Format: Ana Carolina de Carvalho, Danielle C. C. Maia, Andre L. Carvalho, Cristovam Scapulatempo-Neto, Andre L. Vettore. High accuracy of microRNAs expression in the detection of lymph node metastasis in patients with oral squamous cell carcinomas. [abstract]. In: Proceedings of the 104th Annual Meeting of the American Association for Cancer Research; 2013 Apr 6-10; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2013;73(8 Suppl):Abstract nr 5287. doi:10.1158/1538-7445.AM2013-5287