title: Co-regulatory potential of vascular endothelial growth factor-A and vascular endothelial growth factor-C in thyroid carcinoma.
abstract: Vascular endothelial growth factor (VEGF) promotes growth of blood or lymphatic vessels. The aim of the current study is to identify relationships between VEGF-A and VEGF-C, and their impact in angiogenesis and metastases in thyroid cancers. VEGF-A and VEGF-C mRNA and protein expression was investigated in 136 thyroid cancers (123 papillary thyroid carcinomas and 13 undifferentiated thyroid carcinomas) and 40 matched lymph node metastases with papillary thyroid carcinoma using reverse transcription polymerase chain reaction and immunohistochemistry. VEGF-A and VEGF-C mRNA expression was significantly different between conventional papillary thyroid carcinoma, follicular variant of papillary thyroid carcinoma, and undifferentiated thyroid carcinomas (P = 1 × 10(-6) and 1 × 10(-5), respectively). In undifferentiated carcinoma, VEGF-A and VEGF-C protein overexpression was noted in all cases. VEGF-A and VEGF-C mRNA overexpression was noted in 51% (n = 62) and 27% (n = 33) of the papillary thyroid carcinomas, whereas VEGF-A and VEGF-C protein overexpression was also identified in 70% (n = 86) and 62% (n = 76) of the carcinomas. VEGF-A mRNA was significantly higher in cancers with lymph node metastases compared with nonmetastatic cancers (P = .001), whereas most metastatic cancers underexpressed VEGF-C (P = .0002), with a similar trend for protein. The expression of VEGF-A and VEGF-C correlated with each other at both mRNA and protein levels (P = .00004 and .003, respectively). In summary, VEGF-A and -C expressions correlate with the pathological parameters and metastatic status of thyroid carcinomas. The significant correlations between the expressions of these genes add weight to hypotheses concerning VEGF-A and -C interaction in cancer progression.
authors.affiliation: Cancer Molecular Pathology, School of Medicine and Griffith Health Institute, Griffith University, Gold Coast, Queensland 4222, Australia.
authors.forename: Ali
authors.initials: A
authors.lastname: Salajegheh
authors.forename: Sahar
authors.initials: S
authors.lastname: Pakneshan
authors.forename: Atiqur
authors.initials: A
authors.lastname: Rahman
authors.forename: Elliot
authors.initials: E
authors.lastname: Dolan-Evans
authors.forename: Sheldon
authors.initials: S
authors.lastname: Zhang
authors.forename: Esther
authors.initials: E
authors.lastname: Kwong
authors.forename: Vinod
authors.initials: V
authors.lastname: Gopalan
authors.forename: Chung-Yau
authors.initials: CY
authors.lastname: Lo
authors.forename: Robert Anthony
authors.initials: RA
authors.lastname: Smith
authors.forename: Alfred King-Yin
authors.initials: AK
authors.lastname: Lam
mesh_terms: D018263:Adenocarcinoma, Follicular / Q000235:genetics / Q000378:metabolism / Q000556:secondary*; D000328:Adult; D014408:Biomarkers, Tumor / Q000235:genetics / Q000378:metabolism; D002277:Carcinoma / Q000235:genetics / Q000378:metabolism / Q000556:secondary*; D002291:Carcinoma, Papillary; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D008198:Lymph Nodes / Q000378:metabolism / Q000473:pathology; D008207:Lymphatic Metastasis; D008297:Male; D008875:Middle Aged; D009389:Neovascularization, Pathologic / Q000235:genetics / Q000378:metabolism / Q000473:pathology*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D000077273:Thyroid Cancer, Papillary; D013964:Thyroid Neoplasms / Q000235:genetics / Q000378:metabolism / Q000473:pathology* / Q000556:secondary; D042461:Vascular Endothelial Growth Factor A / Q000235:genetics / Q000378:metabolism*; D042582:Vascular Endothelial Growth Factor C / Q000235:genetics / Q000378:metabolism*
chemical_list: D014408:Biomarkers, Tumor; C467484:VEGFA protein, human; C467486:VEGFC protein, human; D042461:Vascular Endothelial Growth Factor A; D042582:Vascular Endothelial Growth Factor C
keywords: Papillary thyroid carcinoma; Undifferentiated carcinoma; VEGF-A; VEGF-C