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. 2009 Jul 9;28(1):98.
doi: 10.1186/1756-9966-28-98.

The role of VEGF-C/D and Flt-4 in the lymphatic metastasis of early-stage invasive cervical carcinoma

Hao Yu  1 , Shiqian Zhang, Renhua Zhang, Linlin Zhang
Affiliations

The role of VEGF-C/D and Flt-4 in the lymphatic metastasis of early-stage invasive cervical carcinoma

Hao Yu et al. J Exp Clin Cancer Res. .

Abstract

Background: To investigate the role of vascular endothelial growth factors (VEGF)-C/D and their receptor Flt-4 in the lymphatic metastasis of early-stage invasive cervical carcinoma.

Methods: Immunohistochemical (IHC) staining with the antibodies against VEGF-C, VEGF-D, and Flt-4 was used to examine the expression of them in 97 cases of early-stage cervical carcinoma (Ia-IIa). Meanwhile, the lymphatic vessel density (LVD) was measured using the antibody against lymphatic vessel endothelial hyaluronan receptor-1 (LYVE-1). We then analyzed the correlation between Flt-4-positive vessel density (FVD), LVD and clinicopathological features of the tumors.

Results: (1) The positive rates of VEGF-C, VEGF-D, and Flt-4 were 57.7%, 60.8%, and 52.6% in the cervical tumor samples, respectively. (2) The expression levels of VEGF-C, VEGF-D, and Flt-4 were significantly correlated with lymphatic metastasis and lymphatic vessel invasion. LVD was significantly associated with lymph node metastasis and lymphatic vessel invasion. On the other hand, FVD was strongly associated with clinical staging. (3) The expression levels of VEGF-C and VEGF-D were significantly correlated with LVD and FVD, while Flt-4 levels showed no correlation with LVD or FVD.

Conclusion: VEGF-C/D and Flt-4 may play an important role in the process of lymphatic metastasis of early-stage invasive cervical carcinoma through paracrine and autocrine mechanisms.

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Figures

Figure 1
Figure 1
The expression of VEGF-C (A), VEGF-D (B), and Flt-4 (C) in cervical carcinoma tissues. A. IHC detection of VEGF-C (→) ×400; B. IHC detection of VEGF-D (→) ×400; and C. IHC detection of Flt-4 (→) ×400.
Figure 2
Figure 2
Morphological features of LYVE-1 positive lymphatic vessels and Flt-4 positive vessels in cervical cancer tissues. A. The LYVE-1 positive lymphatic vessels (→) were clearly different from blood vessels (←) ×200; B. The LYVE-1 positive lymphatic vessels (→) were mainly distributed in the paratumor stromal tissue (←) ×400; C. Some LYVE-1 positive lymphatic vessels contained invaded tumor cells (→) ×400; D. Some Flt-4 positive vessels were similar to blood vessels in their morphology (→), and others were similar to lymphatic vessels (←) ×400; E. The Flt-4 positive vessels (→) were mainly distributed in the paratumor stromal tissue (←) ×400; and F. Some Flt-4 positive vessels contained invaded tumor cells (→) ×400.
See this image and copyright information in PMC

References

    1. Tobler NE, Detmar M. Tumor and lymph node lymphangiogenesis – impact on cancer metastasis. J Leukoc Biol. 2006;80:691–696. doi: 10.1189/jlb.1105653. - DOI - PubMed
    1. Garrafa E, Alessandri G, Benetti A, Turetta D, Corradi A, Cantoni AM, Cervi E, Bonardelli S, Parati E, Giulini SM, Ensoli B, Caruso A. Isolation and characterization of lymphatic microvascular endothelial cells from human tonsils. J Cell Physiol. 2006;207:107–113. doi: 10.1002/jcp.20537. - DOI - PubMed
    1. Juttner S, Wissmann C, Jons T, Vieth M, Hertel J, Gretschel S, Schlag PM, Kemmner W, Hocker M. Vascular endothelial growth factor-D and its receptor VEGFR-3: two novel independent prognostic markers in gastric adenocarcinoma. J Clin Oncol. 2006;24:228–240. doi: 10.1200/JCO.2004.00.3467. - DOI - PubMed
    1. Weidner N, Semple JP, Welch WR, Folkman J. Tumor angiogenesis and metastasis – correlation in invasive breast carcinoma. N Engl J Med. 1991;324:1–8. - PubMed
    1. Jeltsch M, Kaipainen A, Joukov V, Meng X, Lakso M, Rauvala H, Swartz M, Fukumura D, Jain RK, Alitalo K. Hyperplasia of lymphatic vessels in VEGF-C transgenic mice. Science. 1997;276:1423–1425. doi: 10.1126/science.276.5317.1423. - DOI - PubMed

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