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Expression of Vascular Endothelial Growth Factor-C in Benign and Malignant Thyroid Tumors

Endocrine Surgical Oncology Fellows (C.J.H., R.Z., H.K.), Department of Surgery (M.G.W., E.K., O.H.C., Q.Y.D.), University of California San Francisco (UCSF)/Mount Zion Medical Center, Genome Analysis Core Facility (D.G.G.), Cancer Center, UCSF, San Francisco, California 94143; Surgical Service (Q.Y.D.), Veterans Affairs Medical Center, San Francisco, California 94121; and Department of Surgery (C.J.H.), National Cheng Kung University Hospital, Tainan 70441, Taiwan

Address all correspondence and requests for reprints to: Quan-Yang Duh, M.D., Surgical Service, Veterans Affairs Medical Center, 4150 Clement Street, San Francisco, California 94121. E-mail: duhq{at}surgery.ucsf.edu.

In contrast to vascular endothelial growth factor (VEGF), which stimulates angiogenesis, VEGF-C is thought to stimulate lymphangiogenesis. The role of VEGF-C in thyroid cancer pathogenesis has not been clarified. One might expect a different pattern of VEGF-C expression in the various types of thyroid cancer because of their different means of metastases. In this investigation, we determined whether the differential expression of VEGF-C might explain the different propensity to lymph node metastasis in thyroid cancers. One hundred eleven normal and neoplastic thyroid tissues were analyzed by real-time quantitative PCR. Papillary thyroid cancers had a higher VEGF-C expression than other thyroid malignancies (P < 0.0005 ANOVA). Among the normal thyroid tissues from patients with malignant or benign thyroid diseases, there was no significant difference in VEGF-C expression. Paired comparison of VEGF-C expression between thyroid cancers and normal thyroid tissues from the same patients showed a significant increase of VEGF-C expression in papillary thyroid cancer (1.10 ± 0.41 vs. 0.70 ± 0.13; P = 0.001) and a significant decrease of VEGF-C expression in medullary thyroid cancer (0.11 ± 0.13 vs. 0.78 ± 0.29; P = 0.001). In contrast, there was no significant difference of VEGF-C expression between cancer and normal tissues in other types of thyroid cancer. In summary, VEGF-C expression is increased in papillary thyroid cancer, compared with paired normal thyroid tissues, but not in other thyroid cancers that are also prone to lymph node metastasis. The lymphangiogenic role of VEGF-C in thyroid cancers therefore appears to be complex and other factors are likely to be also involved.

This work was supported in part by the Jerold Heller Family Foundation, the Sanford Diller Family Foundation, Ministry of Education in Taiwan, Friends of Endocrine Surgery, and Mt. Zion Health Systems.

Abbreviations: Ct, Cycle threshold; GUS, ß-glucuronidase; VEGF-C, vascular endothelial growth factor-C.

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