Expression of Vascular Endothelial Growth Factor-C in Benign and Malignant Thyroid Tumors
Chung J. Hung,
David G. Ginzinger,
Raza Zarnegar,
Hajime Kanauchi,
Mariwil G. Wong,
Electron Kebebew,
Orlo H. Clark and
Quan-Yang Duh
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), whichstimulates angiogenesis, VEGF-C is thought to stimulate lymphangiogenesis.The role of VEGF-C in thyroid cancer pathogenesis has not beenclarified. One might expect a different pattern of VEGF-C expressionin the various types of thyroid cancer because of their differentmeans of metastases. In this investigation, we determined whetherthe differential expression of VEGF-C might explain the differentpropensity to lymph node metastasis in thyroid cancers. Onehundred eleven normal and neoplastic thyroid tissues were analyzedby real-time quantitative PCR. Papillary thyroid cancers hada higher VEGF-C expression than other thyroid malignancies (P< 0.0005 ANOVA). Among the normal thyroid tissues from patientswith malignant or benign thyroid diseases, there was no significantdifference in VEGF-C expression. Paired comparison of VEGF-Cexpression between thyroid cancers and normal thyroid tissuesfrom the same patients showed a significant increase of VEGF-Cexpression in papillary thyroid cancer (1.10 ± 0.41 vs.0.70 ± 0.13; P = 0.001) and a significant decrease ofVEGF-C expression in medullary thyroid cancer (0.11 ±0.13 vs. 0.78 ± 0.29; P = 0.001). In contrast, therewas no significant difference of VEGF-C expression between cancerand 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 otherthyroid cancers that are also prone to lymph node metastasis.The lymphangiogenic role of VEGF-C in thyroid cancers thereforeappears to be complex and other factors are likely to be alsoinvolved.
This work was supported in part by the Jerold Heller FamilyFoundation, the Sanford Diller Family Foundation, Ministry ofEducation in Taiwan, Friends of Endocrine Surgery, and Mt. ZionHealth Systems.
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