Expression of c-Kit, Flk-1, and Flk-2 Receptors in Benign and Malignant Tumors of Follicular Epithelial Origin

• Published in: Journal of the Chinese Medical Association 2006-02, Vol.69 (2), p.74-79
• Main Authors: Kung, Sung-Pao, Lee, Chen-Hsen, Yang, An-Hang, Chi, Chin-Wen, Tseng, Ling-Ming, Wu, Chew-Wen
• Format: Article
• Language: English
• Subjects: Adenocarcinoma, Follicular - chemistry; Adolescent; Adult; Aged; c-Kit; Carcinoma, Papillary - chemistry; Female; Flk-1; Flk-2; fms-Like Tyrosine Kinase 3 - analysis; fms-Like Tyrosine Kinase 3 - genetics; Humans; Immunohistochemistry; Male; Middle Aged; Proto-Oncogene Proteins c-kit - analysis; Proto-Oncogene Proteins c-kit - genetics; Reverse Transcriptase Polymerase Chain Reaction; Thyroid Neoplasms - chemistry; Thyroid Neoplasms - etiology; Thyroid Neoplasms - pathology; thyroid tumors; Vascular Endothelial Growth Factor Receptor-2 - analysis; Vascular Endothelial Growth Factor Receptor-2 - genetics
• ISSN: 1726-4901; 1728-7731
• DOI: 10.1016/S1726-4901(09)70117-0

Vascular endothelial growth factor (VEGF) is a key regulator of physiologic as well as pathologic angiogenesis. The response of VEGF to endothelial cell mitogenesis and survival, as well as angiogenesis and microvascular permeability, is mainly mediated through its receptor-2, VEGFR2 (kinase domain receptor or fetal liver kinase-1, KDR or Flk-1). This study aimed to detect the expression of VEGFR2 in various forms of thyroid tumors. In addition, the expression of Flk-2 (receptor for Flt-3) and c-Kit (receptor for steel locus factor), which shows strong similarity to Flk-1, was also examined in thyroid tumors. RT-PCR analyses of c-Kit and immunohistochemical staining of c-Kit, Flk-1, and Flk-2 were performed in archived samples of 18 papillary thyroid carcinoma (PTC), 9 follicular thyroid carcinoma (FTC), 12 follicular adenoma (FA), and 7 nodular goiter (NG) samples. The data were correlated to clinicopathologic features. By RT-PCR analyses, c-Kit expression was detected in 22% (4/18) of PTC, 22% (2/9) of FTC, 25% (3/12) of FA, and 57% (4/7) of NG samples. However, positive immunostaining signals of c-Kit were only observed in 17% (3/18) of PTC samples, and not in the others. Similarly, Flk-1 expression was only detected by immunohistochemistry in 67% (12/18) of PTC and 43% (3/7) of NG samples, and not in the others. Interestingly, the expression of Flk-2 was found in 89% (16/18) of PTC, 89% (8/9) of FTC, 75% (9/12) of FA, and 29% (2/7) of NG samples. An inverse relationship of thyroid cancer size with Flk-2 expression was found. Flk-2 expression was detected in various forms of thyroid tumors and increased Flk-2 expression was correlated with thyroid tumors with increased transforming activity, suggesting that Flk-2 is involved in pathogenic development of thyroid malignancy. Similarly, Flk-1 expression was also found in some thyroid tumors, while the expression of c-Kit-mediated pathways may not play a major role in thyroid tumorigenesis.