VASCULAR ENDOTHELIAL GROWTH-FACTOR EXPRESSION IS HIGHER IN DIFFERENTIATED THYROID-CANCER THAN NORMAL OR BENIGN THYROID

Vascular endothelial growth factor (VEGF) is an angiogenic factor, and its expression has been rarely demonstrated in thyroid tumors. We, th erefore, investigated the expression of VEGF messenger RNA (mRNA) and production of VEGF protein in cell lines from human primary and metast atic follicular (FTC-133, FTC-236, and FTC-238), papillary (TPC-1), Hu rthle cell (XTC-1), and medullary thyroid cancers (MTC-1.1 and MTC-2.2 ), and in human thyroid tissues (papillary, follicular, medullary, and Hurthle cell cancers, follicular adenomas, and Graves' thyroid tissue ) by Northern blot, immunohistochemistry, and enzyme-linked immunosorb ent assay (ELISA) studies. All thyroid cell lines expressed a 4.2-kilo base VEGF mRNA. The VEGF mRNA levels were higher in the thyroid cancer cell lines than in primary cultures of normal thyroid cells, and high er in thyroid cancers of follicular than those of parafollicular cell origin. The VEGF mRNA levels were similar in primary and metastatic th yroid tumors. Immunohistochemical staining and Northern blot analysis of the cell lines correlated positively, thus thyroid cancer cell line s stained more intensely than normal thyroid cells and follicular tumo r cells more intensely than parafollicular tumor cells. Again, no diff erence was noted in VEGF staining between primary and metastatic thyro id tumors. Deparafinized sections of papillary, follicular, and Hurthl e cell cancers also stained much stronger than those of medullary thyr oid cancers, benign, or hyperplastic (Graves' disease) thyroid tissue. Thyroid cancer cell lines (XTC-1 > TPC-1 > FTC-133 > MTC-1.1) also se creted more VEGF protein as measured by ELISA than did normal thyroid cells. VEGF secretion of cell lines derived from primary and metastati c thyroid tumors were similar. VEGF mRNA is therefore expressed, and V EGF protein is secreted by normal, hyperplastic, and neoplastic thyroi d tissues. The higher levels of VEGF expression in differentiated thyr oid cancers of follicular cell origin suggests a role in oncogenesis.