BRAF V600E Mutation and X-Linked Inhibitor of Apoptosis Expression in Papillary Thyroid Carcinoma

Abstract

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.