International Journal of Clinical Oncology

, Volume 11, Issue 1, pp 38–43 | Cite as

Expression of vascular endothelial growth factor (VEGF)-C and -D in gastric carcinoma

  • Atsuo Shida
  • Shuichi Fujioka
  • Katsutoshi Kobayashi
  • Yoshio Ishibashi
  • Hiroshi Nimura
  • Norio Mitsumori
  • Katsuhiko Yanaga
ORIGINAL ARTICLE

Abstract

Background

Both vascular endothelial growth factor (VEGF)-C and (VEGF)-D are ligands of VEGF receptor (VEGFR)-3 (Flt-4) and VEGFR-2 (KDR/FLK-1) and are supposed to participate in lymphangiogenesis. The purpose of this study was to clarify the clinical significance of the expression of these factors and to evaluate their relationship with prognosis in patients with gastric carcinoma.

Methods

Fifty pairs of normal mucosa and cancer specimens were obtained from patients who had undergone gastrectomy for primary gastric carcinoma and subjected to reverse transcriptase-polymerase chain reaction for VEGF-C, VEGF-D, and VEGFR-3.

Results

Both VEGF-C and VEGF-D mRNA expression significantly correlated with lymphatic invasion (P < 0.05). Although VEGF-C and -D were concomitantly expressed in most cases, only VEGF-C expression was related to lymph node metastasis. VEGFR-3 expression was associated both with VEGF-C and VEGF-D expression, but not with lymph node metastasis. Tumors expressing these mRNAs tended to correlate with poorer prognosis, but the relationships were not statistically significant.

Conclusion

Our study suggests that both VEGF-C and VEGF-D are involved in lymphatic spreading of gastric cancer cells, which is clinically useful for the evaluation of lymphatic invasion in patients with gastric carcinoma.

Key words

VEGF-C VEGF-D Gastric carcinoma 

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References

  1. 1.
    Parkin, MD, Pisani, P, Felay, J 1999Estimate of worldwide incidence of 25 major cancers in 1990Int J Cancer80827841PubMedGoogle Scholar
  2. 2.
    Adachi, Y, Shiraishi, N, Suematsu, T, Shirimizu, A, Yamaguchi, K, Kitano, S 2000Most important lymoh node information in gastric cancer: multivariate prognostic studyAnn Surg Oncol7503507CrossRefPubMedGoogle Scholar
  3. 3.
    Liotta, LA 1992Cancer cell invasion and metastasisSci Am266545962–63PubMedGoogle Scholar
  4. 4.
    Berse, B, Brown, LF, Van de Water, L, Dvorak, HF, Senger, DR 1992Vascular permeability factor (vascular endothelial growth factor) gene is expressed differentially in normal tissues, macrophages, and tumorsMol Biol Cell3211220PubMedGoogle Scholar
  5. 5.
    Ferrara, N, Houck, K, Jakeman, L, Leung, DW 1992Molecular and biological properties of the vascular endothelial growth factor family of proteinsEndocr Rev131832CrossRefPubMedGoogle Scholar
  6. 6.
    Veikkola, T, Alitalo, K 1999VEGFs, receptors and angiogenesis. (1999)Semin Cancer Biol9211220CrossRefPubMedGoogle Scholar
  7. 7.
    Kaipainen, A, Korhonen, T, van Hinsbergh, VW, Fang, GH, Dumont, D, Breitman, M, Alitalo, K 1995Expression of the fms-like tyrosine kinase 4 gene becomes restricted to lymphatic endothelium during developmentProc Natl Acad Sci U S A9235663570PubMedGoogle Scholar
  8. 8.
    Japanese Research Society for Gastric Cancer1999Japanese classification of gastric carcinomaKaneharaTokyoGoogle Scholar
  9. 9.
    Jeitsch, M, Kaipanen, A, Joukov, V, Meng, X, Lakso, M, Rauvala, H, Swartz, M, Fukumura, D, Jain, RK, Alitalo, K 1997Hyperplasia of lymphatic vessels in VEGF-C transgenic miceScience3014231425Google Scholar
  10. 10.
    Kitadai, Y, Amioka, T, Haruma, K, Tanaka, S, Yoshihara, M, Sumii, K, Matsutani, N, Yasui, W, Chayama, K 2001Clinicopathological significance of vascular endothelial growth factor (VEGF)-C in human esophageal squamous cell carcinomasInt J Cancer93662666CrossRefPubMedGoogle Scholar
  11. 11.
    Yonemura, Y, Endo, Y, Fujita, H, Fushida, S, Ninomiya, I, Bandou, E, Taniguchi, K, Miwa, K, Ohyama, S, Sugiyama, K, Sasaki, T 1999Role of vascular endothelial growth factor C expression in the development of lymph node metastasis in gastric cancerClin Cancer Res518231829PubMedGoogle Scholar
  12. 12.
    Furodoi, A, Tanaka, S, Haruma, K, Kitadai, Y, Yoshihara, M, Chayama, K, Shimamoto, F 2002Clinical significance of vascular endothelial growth factor C expression and angiogenesis at the deepest invasive site of advanced colorectal carcinomaOncology62157166Google Scholar
  13. 13.
    Akagi, K, Ikeda, Y, Miyazaki, M, Abe, T, Kinoshita, J, Maehara, Y, Sugimachi, K 2000Vascular endothelial growth factor- C (VEGF-C) expression in human colorectal tissuesBr J Cancer83887891CrossRefPubMedGoogle Scholar
  14. 14.
    Amioka, T, Kitadai, Y, Tanaka, S, Haruma, K, Yoshihara, M, Yasui, W, Chayama, K 2002Vascular endothelial growth factor-C expression predicts lymph node metastasis of human gastric carcinomas invading the submucosaEur J Cancer3814131419CrossRefPubMedGoogle Scholar
  15. 15.
    Stacker, SA, Caesar, C, Baldwin, ME, Thornton, G, Williams, RA, Prevo, R, Jackson, DG, Nishikawa, S, Kubo, H, Achen, MG 2001VEGF-D promotes the metastatic spread of tumor cells via the lymphaticsNat Med2186191Google Scholar
  16. 16.
    Kurebayashi, J, Otsuki, T, Kunisue, H, Mikami, Y, Tanaka, K, Yamamoto, S, Sonoo, H 1999Expression of vascular endothelial growth factor (VEGF) family members in breast cancerJpn J Cancer Res90977981PubMedGoogle Scholar
  17. 17.
    Achen, MG, Williams, RA, Minekus, MP, Thornton, GE, Stenvers, K, Rpgers, PA, Lederman, F, Roufail, S, Stacker, SA 2001Localization of vascular endothelial growth factor-D in malignant melanoma suggests a role in tumour angiogenesisJ Pathol193147154CrossRefPubMedGoogle Scholar
  18. 18.
    Onogawa, S, Kitadai, Y, Taknaka, S, Toshio, K, Kimura, S, Chayama, K 2004Expression of VEGF-C and VEGF-D at the invasive edge correlates with lymph node metastasis and prognosis of patients with colorectal carcinomaCancer Sci953239CrossRefPubMedGoogle Scholar
  19. 19.
    Ishikawa, M, Kitayama, J, Kazama, S,  et al. 2003Expression of vascular endothelial growth factor (VEGF-C and -D) is an important risk factor for lymphatic metastasis in undifferentiated early gastric carcinomaJpn J Clin Oncol332127PubMedGoogle Scholar
  20. 20.
    Shimizu, K, Kubo, H, Yamaguchi, K, Kawashima, K, Ueda, Y, Matsuo, K, Awane, M, Shimahara, Y, Takabayashi, A, Yamaoka, Y, Satoh, S 2004Suppression of VEGFR-3 signaling inhibits lymph node metastasis in gastric cancerCancer Sci95328333CrossRefPubMedGoogle Scholar

Copyright information

© The Japan Society of Clinical Oncology 2006

Authors and Affiliations

  • Atsuo Shida
    • 1
  • Shuichi Fujioka
    • 1
  • Katsutoshi Kobayashi
    • 1
  • Yoshio Ishibashi
    • 1
  • Hiroshi Nimura
    • 1
  • Norio Mitsumori
    • 1
  • Katsuhiko Yanaga
    • 1
  1. 1.Department of SurgeryJikei University School of MedicineTokyoJapan

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