title: Relationship between LYVE-1, VEGFR-3 and CD44 gene expressions and lymphatic metastasis in gastric cancer.
abstract: OBJECTIVE
  To investigate the expression levels of lymphatic vessel endothelial hyaluronan receptor-1 (LYVE-1), vascular endothelial growth factor receptor-3 (VEGFR-3) and CD44 genes and the relationship between their levels and clinicopathological parameters in gastric cancer.
  
  
  METHODS
  Tissue samples were obtained from 33 patients (8 females) with gastric cancer. mRNA levels of LYVE-1, VEGFR-3 and CD44 in normal and tumor tissues were quantitatively measured using real time polymerase chain reaction. The results were correlated with lymph node metastasis, histological type and differentiation of the tumor, T-stage, and presence of vascular, perineural and lymphatic invasions. The distribution of molecules in the tissue was evaluated using immunohistochemistry.
  
  
  RESULTS
  LYVE-1, CD44 and VEGFR-3 gene expression levels were significantly higher in gastric cancer than in normal tissue. While there was no correlation between gene expressions and clinicopathologic features such as histologic type, differentiation and stage, gene expression levels were found to be increased in conjunction with positive lymph node/total lymph node ratio and the presence of perineural invasion. A significant correlation was also found between LYVE-1 and CD44 over-expressions and perineural invasion and lymph node positivity in gastric cancers. When the distribution of LYVE-1 antibody-stained lymphatic vessels in tissue was evaluated, lymphatic vessels were located intra-tumorally in 13% and peri-tumorally in 27% of the patients. Moreover, lymph node metastases were also positive in all patients with LYVE-1-staining.
  
  
  CONCLUSIONS
  LYVE-1, VEGFR-3 and CD44 all play an important role in lymphangiogenesis, invasion and metastasis. LYVE-1 is a perfectly reliable lymphatic vessel marker and useful for immunohistochemistry.
authors.affiliation: Department of Basic Oncology, Hacettepe University Institute of Oncology, 06100 Ankara, Turkey. fusun.ozmen@hacettepe.edu.tr
authors.forename: Fusun
authors.initials: F
authors.lastname: Ozmen
authors.forename: M Mahir
authors.initials: MM
authors.lastname: Ozmen
authors.forename: Evren
authors.initials: E
authors.lastname: Ozdemir
authors.forename: Munevver
authors.initials: M
authors.lastname: Moran
authors.forename: Selda
authors.initials: S
authors.lastname: Seçkin
authors.forename: Dicle
authors.initials: D
authors.lastname: Guc
authors.forename: Ergun
authors.initials: E
authors.lastname: Karaagaoglu
authors.forename: Emin
authors.initials: E
authors.lastname: Kansu
mesh_terms: D000328:Adult; D000368:Aged; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D018960:Hyaluronan Receptors / Q000096:biosynthesis*; D007150:Immunohistochemistry / Q000379:methods; D008207:Lymphatic Metastasis; D008297:Male; D008875:Middle Aged; D011379:Prognosis; D012333:RNA, Messenger / Q000378:metabolism; D013274:Stomach Neoplasms / Q000378:metabolism*; D040321:Vascular Endothelial Growth Factor Receptor-3 / Q000096:biosynthesis*; D033921:Vesicular Transport Proteins / Q000096:biosynthesis*
chemical_list: C497483:CD44 protein, human; D018960:Hyaluronan Receptors; C119248:LYVE1 protein, human; D012333:RNA, Messenger; D033921:Vesicular Transport Proteins; D040321:Vascular Endothelial Growth Factor Receptor-3