title: Association of the T1799A BRAF mutation with tumor extrathyroidal invasion, higher peripheral platelet counts, and over-expression of platelet-derived growth factor-B in papillary thyroid cancer.
abstract: The relationship among BRAF mutation, platelet counts, and platelet-derived growth factor (PDGF) with respect to clinicopathological outcomes of papillary thyroid cancer (PTC) may play a role in PTC pathogenesis but remains undefined. We examined the T1799A BRAF mutation by direct genomic DNA sequencing in 108 primary PTC samples from a Chinese cohort and analyzed its relationship with clinicopathological, hematological, and other laboratory results as well as the levels of expression of PDGF in tumors. We found that the BRAF mutation was significantly associated with extrathyroidal invasion and advanced tumor stages III and IV. Specifically, extrathyroidal invasion was seen in 30/54 (56%) PTC with BRAF mutation versus 18/54 (33%) PTC without the mutation (P=0.02). Tumor stages III and IV were seen in 16/54 (30%) PTC with BRAF mutation versus 7/54 (13%) PTC without the mutation (P=0.04). The BRAF mutation was also significantly associated with a higher platelet count, with 249.28+/-53.76 x 10(9)/l in the group of patients with BRAF mutation versus 207.79+/-58.98 x 10(9)/l in the group without the mutation (P=0.001). An association of higher platelet accounts with extrathyroidal invasion was also seen, with 242.66+/-51.85 x 10(9)/l in patients with extrathyroidal invasion versus 218.49+/-59.10 x 10(9)/l in patients without extrathyroidal invasion (P=0.03). The BRAF T1799A-positive PTC tissues harbored a significantly higher level of PDGF-B than BRAF T1799A-negative PTC tissues. The data suggest that the BRAF T1799A mutation is associated with aggressive pathological outcomes of PTC in which high platelet counts and increased PDGF production may play a role.
authors.affiliation: Division of Endocrinology and Metabolism, The Johns Hopkins University School of Medicine, Baltimore, MD 21287, USA.
authors.forename: Yangang
authors.initials: Y
authors.lastname: Wang
authors.forename: Meiju
authors.initials: M
authors.lastname: Ji
authors.forename: Wei
authors.initials: W
authors.lastname: Wang
authors.forename: Zhimin
authors.initials: Z
authors.lastname: Miao
authors.forename: Peng
authors.initials: P
authors.lastname: Hou
authors.forename: Xinyan
authors.initials: X
authors.lastname: Chen
authors.forename: Feng
authors.initials: F
authors.lastname: Xu
authors.forename: Guangwu
authors.initials: G
authors.lastname: Zhu
authors.forename: Xianlu
authors.initials: X
authors.lastname: Sun
authors.forename: Yujun
authors.initials: Y
authors.lastname: Li
authors.forename: Steven
authors.initials: S
authors.lastname: Condouris
authors.forename: Dingxie
authors.initials: D
authors.lastname: Liu
authors.forename: Shengli
authors.initials: S
authors.lastname: Yan
authors.forename: Jie
authors.initials: J
authors.lastname: Pan
authors.forename: Mingzhao
authors.initials: M
authors.lastname: Xing
mesh_terms: D000231:Adenocarcinoma, Papillary / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D000328:Adult; D002681:China / Q000453:epidemiology; D015331:Cohort Studies; D017931:DNA Primers; D004273:DNA, Neoplasm / Q000235:genetics; D018450:Disease Progression; D005260:Female; D006801:Humans; D007124:Immunoenzyme Techniques; D008207:Lymphatic Metastasis; D008297:Male; D008875:Middle Aged; D009154:Mutation / Q000235:genetics*; D009361:Neoplasm Invasiveness; D010976:Platelet Count; D016133:Polymerase Chain Reaction; D011379:Prognosis; D048493:Proto-Oncogene Proteins B-raf / Q000235:genetics*; D020574:Proto-Oncogene Proteins c-sis / Q000378:metabolism*; D012189:Retrospective Studies; D013964:Thyroid Neoplasms / Q000235:genetics* / Q000378:metabolism / Q000473:pathology
chemical_list: D017931:DNA Primers; D004273:DNA, Neoplasm; D020574:Proto-Oncogene Proteins c-sis; C482119:BRAF protein, human; D048493:Proto-Oncogene Proteins B-raf