Expression of X-linked Inhibitor of Apoptosis Protein in Neoplastic Thyroid Disorder

Abstract

X-linked inhibitor of apoptosis protein (XIAP) is associated with tumor genesis, growth, progression and metastasis, and acts by blocking caspase-mediated apoptosis. In the present study, we sought to evaluate the expression patterns of XIAP in various neoplastic thyroid disorders and determine the association between XIAP expression and clinicopathologic factors. We additionally evaluated the association of XIAP expression and the BRAFV600E mutation and analyzed the association of XIAP expression and tumor recurrence in BRAFV600E prevalent PTC population. Expression of XIAP was evaluated with immunohistochemical staining using monoclonal anti-XIAP in 164 specimens of conventional papillary thyroid carcinoma (PTC) and 53 specimens of other malignant or benign thyroid tumors. The presence of the BRAFV600E mutation was evaluated using PCR amplification and direct sequencing in 164 specimens of conventional PTC. XIAP positivity was observed in 128 (78%) of the 164 conventional PTC specimens. Positive rates of XIAP expression in follicular variant PTC, follicular, medullary, poorly differentiated, and anaplastic thyroid carcinoma specimens were 20%, 25%, 38%, 67%, and 38%, respectively. Six nodular hyperplasia specimens were negative and 1 of 7 follicular adenomas (8%) was positive for XIAP. Lateral lymph node metastases were more frequent in patients negative for XIAP expression (P=0.01). The BRAFV600E mutation was found in 123 of 164 conventional PTCs (75%). XIAP expression was significantly higher in BRAFV600E mutated PTC than that in wild type PTC. (p=0.03). Negative XIAP expression were significantly associated with tumor recurrence in patients with BRAFV600E mutation (p = 0.03). Immunohistochemical staining for XIAP as a novel molecular marker may thus be helpful in the differential diagnosis of thyroid cancer and high XIAP expression in conventional PTC is strongly associated with reduced risk of lateral lymph node metastasis. Moreover, negative XIAP expression was associated with lateral lymph node metastases and an increased risk of recurrence in BRAF mutated PTC patients. XIAP immunohistochemical staining is useful for predicting patient prognosis in in BRAFV600E prevalent PTC population.