Association Between Expression of X-Linked Inhibitor of Apoptosis Protein and the Clinical Outcome in a BRAFV600E-Prevalent Papillary Thyroid Cancer Population

Abstract

The X-linked inhibitor of apoptosis protein (XIAP) is associated with carcinogenesis, cancer progression, and metastasis through inhibition of the caspase-mediated apoptotic pathway. The BRAF(V600E) mutation is the most common genetic alteration and an established prognostic marker in papillary thyroid cancer (PTC). The prevalence of the BRAF mutation is very high and is up to 80% in Korean PTC patients. In the present study, we evaluated the potential role of XIAP expression as a novel prognostic marker to predict recurrence, in combination with the BRAF(V600E) mutational status. The study enrolled 164 patients with conventional PTC who underwent bilateral thyroidectomy followed by immediate (131)I ablation. The presence of the BRAF(V600E) mutation was evaluated by direct sequencing. The degree of XIAP expression was evaluated by immunohistochemical (IHC) staining using a monoclonal antibody. The BRAF(V600E) mutation was found in 123 of 164 patients (75%) with classical PTC. XIAP expression was positive in 128 of 164 patients (75%), and positive XIAP expression was significantly associated with the presence of lateral cervical lymph node metastases (p=0.01). XIAP expression was more frequent in BRAF(V600E) mutated PTCs than in BRAF wild type PTCs (p=0.048). The BRAF(V600E) mutation was significantly associated with cancer recurrence in study subjects (hazard ratio=2.98, p=0.039). PTCs positive for the BRAF(V600E) mutation but negative for XIAP expression had a significantly higher rate of recurrent PTC (hazard ratio=4.53, p=0.012). The evaluation of XIAP expression and BRAF mutational analysis was more useful for the prediction of cancer recurrence in patients with PTC than BRAF genotype alone.