Research Paper
Expression of vascular endothelial growth factor-C does not predict occult lymph-node metastasis in early oral squamous cell carcinoma

https://doi.org/10.1016/j.ijom.2007.11.021Get rights and content

Abstract

Strong vascular endothelial growth factor-C (VEGF-C) expression has been correlated to occurrence of lymph-node metastases in patients with oral squamous cell carcinoma (OSCC). The incidence of occult lymph-node metastasis remains a decisive factor in the prognosis of patients with early OSCC. The aim of this study was to evaluate VEGF-C expression as a predictor of occult lymph-node metastasis in OSCC. Eighty-seven patients with primary OSCC arising in the tongue or floor of mouth, clinically T1N0M0 or T2N0M0, with (pN+) and without (pN0) occult lymph-node metastases were analyzed for VEGF-C expression by malignant cells. Occult lymph-node metastases (pN+) were detected in 22% of the 64 patients who were submitted to elective neck dissection. No statistically significant difference was found between OSCC with and without occult lymph-node metastasis in regard to VEGF-C immunoexpression by malignant cells and clinicopathologic features. Independently of VEGF-C expression, lymph-node metastasis (pN+) was the most significant prognostic factor for overall survival of patients with OSCC (p = 0.030). These findings indicate that isolated VEGF-C expression by malignant cells is not of predictive value for occult lymph-node metastasis in the early stages of OSCC.

Section snippets

Patient and tumor samples

This study was based on the analysis of 87 patients (68 males and 19 females) who underwent surgical treatment for primary OSCC from 1968 to 2001, at the Head and Neck Surgery and Otorhinolaryngology Department of the A.C. Camargo Cancer Hospital, Brazil. The inclusion criteria were: (1) primary OSCC located in the tongue or floor of mouth, clinical stages I (T1N0M0) and II (T2N0M0), confirmed by biopsy; (2) patients who did not undergo radiotherapy, chemotherapy or other treatment prior to

Clinical features

The analysis of 87 patients with OSCC revealed a white male predominance with frequently tobacco (83%) and/or alcohol (76%) consumption. The patients’ ages ranged from 35 to 89 years (mean 59.36 years ±10.91 standard deviation [SD]). The tumor was located in the tongue (69% of cases) and floor of the mouth (31% of cases). On the basis of the Union Internationale Contre le Cancer38, 39 criteria of oral cavity carcinomas, a total of 28 cases (32%) were at clinical stage I (T1N0M0) and 59 (68%)

Discussion

Although the metastatic dissemination of tumor cells to regional lymph nodes is a common feature of OSCC arising in the tongue and floor of mouth, it is not clear whether the tumor utilizes existing lymphatic channels or whether dissemination requires the formation of new lymphatic vessels (lymphangiogenesis)4, 8, 18, 27, 32, 34.

In the last decade, VEGF-C and VEGF-D were identified as lymphangiogenic growth factors and ligands to the receptor VEGFR-3 present in the lymphatic vessels9, 15, 23, 29

Acknowledgments

The authors thank FAPESP (Fundação de Amparo à Pesquisa do Estado de São Paulo, grant #2005/04577-4) and CAPES (Coordenação de Aperfeiçoamento de Pessoal de Nível Superior) for supporting this study.

References (44)

  • T.M.P. Amaral et al.

    Predictive factors of occult metastasis and prognosis of clinical stages I and II squamous cell carcinoma of the tongue and floor of the mouth

    Oral Oncol

    (2004)
  • M. Arinaga et al.

    Clinical significance of vascular endothelial growth factor C and vascular endothelial growth factor receptor 3 in patients with nonsmall cell lung carcinoma

    Cancer

    (2003)
  • A. Bànkfalvi et al.

    Prognostic and predictive factors in oral cancer: the role of invasive tumor front

    J Oral Path Med

    (2000)
  • N.J.P. Beasley et al.

    Intratumoral lymphangiogenesis and lymph node metastasis in head and neck cancer

    Cancer Res

    (2002)
  • M. Bryne et al.

    The invasive front of carcinomas. The most important area for tumour prognosis?

    Anticancer Res

    (1998)
  • M. Bryne et al.

    New malignancy grading is a better prognostic indicator than Broders’ grading in oral squamous cell carcinoma

    J Oral Pathol Med

    (1989)
  • R.M. Byers et al.

    Can we detect or predict the presence of occult nodal metastases in patients with squamous carcinoma of the oral tongue?

    Head Neck

    (1998)
  • R. Clarijs et al.

    Lymphangiogenesis in malignant tumours: does it occur?

    J Pathol

    (2001)
  • N. Ferrara et al.

    The biology of vascular endothelial growth factor

    Endocr Rev

    (1997)
  • K.J. Haddadin et al.

    Improved survival for patients with clinically T1/T2, N0 tongue tumors undergoing a prophylactic neck dissection

    Head Neck

    (1999)
  • K. Kishimoto et al.

    Expression of vascular endothelial growth factor-C predicts regional lymph node metastasis in early oral squamous cell carcinoma

    Oral Oncol

    (2003)
  • Kowalski LP, Magrin J, Sab_oia M, Santos JC, Torloni H. Squamous cell carcinoma of the tongue: a review of 629 patients...
  • L.P. Kowalski et al.

    Nodal metastases: predictive factors

    Otolaryngol Clin North Am

    (1998)
  • J. Krishnan et al.

    Differential in vivo and in vitro expression of vascular endothelial growth factor (VEGF)-C and VEGF-D in tumors and its relationship to lymphatic metastasis in immunocompetent rats

    Cancer Res

    (2003)
  • E. Kukk et al.

    VEGF-C receptor binding, and pattern of expression with VEGFR-3 suggests a role in lymphatic vascular development

    Development

    (1996)
  • Q.L. Li et al.

    Expression and clinical significance of VEGF-C and Flt-4 in tongue squamous cell carcinoma

    Ai Zheng

    (2006)
  • R. López De Cicco et al.

    Simultaneous expression of furin and vascular endothelial growth factor in human oral tongue squamous cell carcinoma progression

    Clin Cancer Res

    (2004)
  • M.F. Munoz-Guerra et al.

    Prognostic significance of intratumoral lymphangiogenesis in squamous cell carcinoma of the oral cavity. A study of the early stages

    Cancer

    (2004)
  • Y. Nakamura et al.

    Clinicopathological significance of vascular endothelial growth factor-C in breast carcinoma with long-term follow-up

    Mod Pathol

    (2003)
  • H. Nakaya et al.

    Influences of angiogenesis and lymphangiogenesis on cancerous invasion in experimentally induced tongue carcinoma

    J Oral Pathol Med

    (2005)
  • T. Nakazato et al.

    Expression level of vascular endothelial growth factor-C and -A in cultured human oral squamous cell carcinoma correlates respectively with lymphatic metastasis and angiogenesis when transplanted into nude mouse oral cavity

    Oncol Rep

    (2006)
  • C. Neuchrist et al.

    Vascular endothelial growth factor C and vascular endothelial growth factor receptor 3 expression in squamous cell carcinomas of the head and neck

    Head Neck

    (2003)

    • Cited by (0)

    View full text
    Copyright © 2007 International Association of Oral and Maxillofacial Surgeons. Published by Elsevier Ltd. All rights reserved.