Original Article
Copyright ©2011 Baishideng Publishing Group Co., Limited. All rights reserved.
World J Gastroenterol. Jul 21, 2011; 17(27): 3220-3228
Published online Jul 21, 2011. doi: 10.3748/wjg.v17.i27.3220
Relationship between LYVE-1, VEGFR-3 and CD44 gene expressions and lymphatic metastasis in gastric cancer
Fusun Ozmen, M Mahir Ozmen, Evren Ozdemir, Munevver Moran, Selda Seçkin, Dicle Guc, Ergun Karaagaoglu, Emin Kansu
Fusun Ozmen, Dicle Guc, Emin Kansu, Department of Basic Oncology, Hacettepe University Institute of Oncology, 06100 Ankara, Turkey
M Mahir Ozmen, Munevver Moran, Department of General Surgery, Ankara Numune Teaching and Research Hospital, 06100 Ankara, Turkey
M Mahir Ozmen, Department of Emergency Medicine, Hacettepe University Medical School, 06100 Ankara, Turkey
Evren Ozdemir, Department of Medical Oncology, Hacettepe University Institute of Oncology, 06100 Ankara, Turkey
Selda Seçkin, Department of Pathology, Ankara Numune Teaching and Research Hospital, 06100 Ankara, Turkey
Ergun Karaagaoglu, Department of Biostatistics and Medical Informatics, Hacettepe University Faculty of Medicine, 06100 Ankara, Turkey
Author contributions: Ozmen F and Ozmen MM contributed equally to this work; Ozmen F, Ozmen MM, Ozdemir E, Guc D and Kansu E designed the research and provided the protocols; Ozmen F, Ozmen MM, Seçkin S and Moran M performed the research and collected the data; Karaagaoglu E and Ozmen F analyzed the data; Ozmen F, Ozmen MM and Ozdemir E wrote the paper.
Supported by TUBİTAK-SBAG (Project Number 104S581); the Turkish Academy of Sciences (TUBA)
Correspondence to: Fusun Ozmen, MD, MSci, PhD, Department of Basic Oncology, Hacettepe University Institute of Oncology, Hacettepe, 06100 Ankara, Turkey. fusun.ozmen@hacettepe.edu.tr
Telephone: +90-312-3054322 Fax: +90-312-3242009
Received: October 14, 2010
Revised: December 5, 2010
Accepted: December 12, 2010
Published online: July 21, 2011
Abstract

AIM: 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.

CONCLUSION: 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.

Keywords: CD44; Gastric cancer; Lymphatic metastasis; Lymphatic vessel endothelial hyaluronan receptor-1; Metastasis; Vascular endothelial growth factor receptor-3