Abstract 5079: A genomic copy number biomarker to identify oral cancer patients at low risk for metastasis

Abstract

Abstract The biologic behavior of oral dysplasia (precancers) and squamous cell carcinoma (SCC) is unpredictable, the main problems in management being identification of patients at risk for metastasis or risk of progression of dysplasias to cancer. Neck metastasis, the most significant clinical factor causing death in oral SCC, reduces survival by 50%. We utilized array comparative genomic hybridization (CGH) to clarify the role of genomic aberrations in oral cancer progression and metastasis. Two oral SCC cohorts: cohort#1, n=89 (Snijders et al, 2005)) and cohort#2, n=63 (with associated pathologic nodal status and 5 year clinical follow up) were profiled using BAC CGH arrays. Two dysplasia cohorts, one with no association to cancer (cohort D1, n=29) and one associated with previous or subsequent cancer (cohort D2, n=10) were also profiled for recurrent copy number aberrations using array CGH. Associations with clinical characteristics were studied and results confirmed in an independent SCC cohort (cohort#3, n=14, Smeets et al., 2009). All samples used in this study were restricted to oral cavity sites only and were archival formalin fixed paraffin embedded tissue. Copy number alterations distinguished two oral dysplasia and cancer subtypes. The presence of one or more of the chromosomal aberrations +3q24-qter, -8pter-p23.1, +8q12-q24.2, and +20 distinguished a major subgroup (70%-80% of lesions, termed 3q8pq20 subtype) from the remainder (20%-30% of lesions, non-3q8pq20). Most notably, 3q8pq20 and non-3q8pq20 subtypes differed significantly in clinical outcome with risk for cervical (neck) lymph node metastasis almost exclusively associated with the 3q8pq20 subtype in two independent oral SCC cohorts (cohort#2 and cohort#3). As metastasis to the cervical lymph nodes is a major determinant of survival in oral SCC patients, our findings indicate that chromosomal aberrations +3p, -8p, +8q and +20 provide a potential biomarker to identify patients at no or low risk of metastasis. The negative predictive value (NPV) i.e. the ability to predict N0 cases at biopsy was 93% for cohort#2 and 100% in cohort#3. Currently, almost all patients diagnosed with oral SCC are treated with comprehensive neck dissection at the time of tumor resection, as salvage of patients who subsequently develop neck metastasis is poor. We propose that the +3q, -8p, +8q and +20 signature is suitable for stratifying patients for risk of metastasis prior to surgery, and so can guide surgical treatment for one of the most challenging treatment decisions - how to treat patients with clinically node-negative (N0) necks. Identification of patients with low risk for metastasis would spare them additional major surgery with its risks and morbidity, as well as reduce medical costs. 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 5079. doi:1538-7445.AM2012-5079