Association of XIAP and P2X7 receptor expression with lymph node metastasis in papillary thyroid carcinoma.

The expression of X-linked inhibitor of apoptosis (XIAP) and the P2X7 receptor were demonstrated in a variety of tumors. The purpose of the present study was to investigate the associations of XIAP and P2X7 receptor expression with the clinicopathological features of patients with papillary thyroid carcinoma (PTC). In this cross-sectional study, a total of 62 cases were examined, including 43 patients with PTCs and 19 with benign nodular goiters. XIAP and P2X7 receptor expression were examined by immunohistochemical methods on formalin-fixed, paraffin-embedded thyroid tissues. The staining intensity and extent were evaluated and scored using a semi-quantitative method. The immunohistochemical staining score integrating the intensity and extent of XIAP and P2X7 receptors in PTCs was higher than in nodular goiters. XIAP (OR: 5.6, 95% CI: 1.5-21.1, P=0.009) and P2X7 receptor (OR: 6.1, 95% CI: 1.5-24.4, P=0.007) expression were associated with lymph node metastasis in PTCs. In logistic regression analysis, P2X7 receptor expression, tumor size, and capsular infiltration were predictors for lymph node metastasis (P=0.001). Our results suggested that XIAP and P2X7 receptor expression may predict the aggressiveness of PTC.

BRAFV600E mutation and X-linked inhibitor of apoptosis expression in papillary thyroid carcinoma.

BACKGROUND: The BRAF mutation V600E (BRAF(V600E)) is the most common genetic alteration in papillary thyroid carcinoma (PTC), while overexpression of X-linked inhibitor of apoptosis (XIAP) has been found in various tumors. Both of these events are implicated in carcinogenesis, tumor progression, recurrence, etc. There are few reports, however, of the BRAF(V600E) mutation and XIAP overexpression in PTC patients. The aim of this study was to investigate the frequency of the BRAF(V600E) mutation in PTC and its relationship to clinicopathological parameters and the expression of XIAP. METHODS: Genomic DNA was extracted from 123 paraffin-embedded PTC tumor tissue samples and amplified for analysis of the V600E mutation in exon 15 of the BRAF gene by polymerase chain reaction. XIAP expression was examined by immunohistochemical methods in 46 PTCs, 18 benign nodular goiters, and 10 Hashimoto's thyroiditis samples. RESULTS: The BRAF(V600E) mutation was found in 34.1% of PTC, and was especially prevalent in the classic type. BRAF(V600E) was significantly correlated with younger age at diagnosis (p = 0.026), tumor size (p = 0.009), and histological variants (p = 0.024). There was a trend towards association with extrathyroidal invasion (p = 0.067). By logistic regression analysis, a significant relationship was found between tumor size and the BRAF(V600E) mutation (p = 0.03). XIAP was expressed in 82.6% of PTCs, which was a higher percentage than observed in the group of benign thyroid disorders (35.7%, p < 0.001). Neither the intensity (p = 0.611) nor the extent (p = 0.723) of XIAP staining was correlated with the presence of BRAF(V600E) in PTC patients. CONCLUSIONS: These data indicate that BRAF(V600E) is associated some of the aggressive clinicopathological features of PTC including younger age at diagnosis, larger tumor size, and classic histological type, as well as also extrathyroidal invasion. XIAP-positive staining was more prevalent in PTCs than in the benign thyroid disorders. Although BRAF(V600E) and XIAP expression are commonly seen in PTC, their presence together seems unrelated.