Fellmer P T, Sato K, Tanaka R, Okamoto T, Kato Y, Kobayashi M, Shibuya M, Obara T
Department of Endocrine Surgery, Institute of Clinical Endocrinology, Tokyo, Japan.
Surgery. 1999 Dec;126(6):1056-61; discussion 1061-2. doi: 10.1067/msy.2099.101432.
Vascular endothelial growth factor-C (VEGF-C) is known to be related to development of lymphatic vessels. Papillary thyroid carcinoma characteristically metastasizes to regional lymph nodes, whereas follicular thyroid carcinoma commonly spreads hematogenously. The present study was designed to determine whether expression of the VEGF-C gene is related to the different metastatic features of these 2 types of thyroid carcinoma.
Thyroid carcinoma specimens were obtained from 15 patients with papillary carcinoma and 4 patients with follicular carcinoma of the thyroid. VEGF-C gene expression was examined by Northern blotting and in situ hybridization. Immunohistochemistry was performed to localize the deposition of VEGF-C protein.
The ratios of VEGF-C gene expression determined by Northern blot analysis were significantly higher in papillary than in follicular carcinoma. Nonmalignant thyroid tissue from patients with papillary carcinoma also expressed higher levels of VEGF-C than tissue from patients with follicular carcinoma. Expression of the VEGF-C gene was observed by in situ hybridization in cells of papillary thyroid carcinoma but not in those of follicular carcinoma. Positive staining with antibody against VEGF-C was detected in papillary cancer cells.
Concurrent overexpression of the VEGF-C gene by both tumor cells and the surrounding tissue may be related to the prevalence of intrathyroidal spread through lymphatics and regional lymph node metastasis in patients with papillary thyroid carcinoma.
血管内皮生长因子C(VEGF-C)已知与淋巴管发育有关。甲状腺乳头状癌的特征是转移至区域淋巴结,而甲状腺滤泡癌通常通过血行播散。本研究旨在确定VEGF-C基因的表达是否与这两种类型甲状腺癌的不同转移特征相关。
从15例甲状腺乳头状癌患者和4例甲状腺滤泡癌患者获取甲状腺癌标本。通过Northern印迹法和原位杂交检测VEGF-C基因表达。进行免疫组织化学以定位VEGF-C蛋白的沉积。
通过Northern印迹分析确定的VEGF-C基因表达率在乳头状癌中显著高于滤泡癌。甲状腺乳头状癌患者的非恶性甲状腺组织也比滤泡癌患者的组织表达更高水平的VEGF-C。通过原位杂交在甲状腺乳头状癌细胞中观察到VEGF-C基因的表达,而在滤泡癌细胞中未观察到。在乳头状癌细胞中检测到抗VEGF-C抗体的阳性染色。
肿瘤细胞和周围组织同时过度表达VEGF-C基因可能与甲状腺乳头状癌患者甲状腺内通过淋巴管扩散和区域淋巴结转移的发生率有关。