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Submitted on December 30, 2005
Accepted on June 5, 2006
Division of Endocrinology, Department of Internal Medicine, Department of Pathology, Department of Surgery, Chungnam National University School of Medicine, 640 Daesadong Chungku Daejeon 301-721 Korea. Department of Biochemistry, Seonam University College of Medicine, Namwon 590-711 Korea
* To whom correspondence should be addressed. E-mail: minhos{at}cnu.ac.kr.
Context: The BRAF mutation may influence the expression patterns of molecular markers which are related to the development and progression of thyroid cancer.
Objective: To investigate the effects of the BRAF V600E mutation on expression of galectin-3, cyclooxygenase-2 (COX-2), cyclin D1, p53 and vascular endothelial growth factor (VEGF) in papillary thyroid cancer (PTC).
Design, Setting, and Subjects: 163 PTC and 28 nodular hyperplasia (NH) patients were selected retrospectively. The presence of the BRAF V600E mutation and the level of expression of the molecular markers was determined.
Results: Of 161 PTC patients, 102 patients (63.4%) were BRAF V600E(+) and these cases had significantly larger tumor sizes (P = 0.01) compared with V600E(-) cases (n = 59, 36.6%). Although PTC tissues had higher expression levels of the selected molecular markers than NH tissues, expression levels of several molecular markers in BRAF V600E(+) PTC were not significantly different from those of BRAF V600E(-) PTC. But, VEGF was significantly up-regulated in BRAF V600E(+) PTC compared with BRAF V600E(-) PTC. VEGF expression levels were strongly positively correlated to tumor size (P < 0.001), extra-thyroidal invasion (P = 0.02), and tumor stage (P = 0.04). Multivariate analysis clearly showed that VEGF expression was up-regulated in BRAF V600E(+) PTC (OR = 2.5, CI, 1.1 - 5.6; P = 0.03).
Conclusions: BRAF V600E(+) PTC tended to have larger tumor volumes and higher expression of VEGF. The level of VEGF expression was closely correlated with tumor size, extra-thyroidal invasion and stage. The relatively high levels of VEGF expression may be related to poorer clinical outcomes and recurrences in BRAF V600E(+) PTC.
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