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.
Department of Endocrine and Metabolic Diseases, Rui-jin Hospital, Shanghai Jiao-tong University School of Medicine, Shanghai, China.
Li-Qun
LQ
Gu
Feng-Ying
FY
Li
Lin
L
Zhao
Yun
Y
Liu
Xun-Xiong
XX
Zang
Tian-Xiang
TX
Wang
Hui-Ping
HP
Chen
Guang
G
Ning
Yong-Ju
YJ
Zhao
D000328:Adult; D019943:Amino Acid Substitution; D002291:Carcinoma, Papillary / Q000235:genetics* / Q000473:pathology; D005260:Female; D006044:Goiter, Nodular / Q000235:genetics; D050031:Hashimoto Disease / Q000235:genetics; D006801:Humans; D008297:Male; D008875:Middle Aged; D009361:Neoplasm Invasiveness / Q000235:genetics; D048493:Proto-Oncogene Proteins B-raf / Q000235:genetics*; D013964:Thyroid Neoplasms / Q000235:genetics* / Q000473:pathology; D051636:X-Linked Inhibitor of Apoptosis Protein / Q000235:genetics*
D051636:X-Linked Inhibitor of Apoptosis Protein; C496866:XIAP protein, human; C482119:BRAF protein, human; D048493:Proto-Oncogene Proteins B-raf