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Tumor-Associated Lymphangiogenesis Correlates with Prognosis after Resection of Human Hepatocellular Carcinoma

  • Hepatobiliary and Pancreatic Tumors
  • Published:
Annals of Surgical Oncology Aims and scope Submit manuscript

Abstract

Background

Experimental results from animal models as well as studies of human cancers indicate a critical role for tumor-associated lymphangiogenesis in tumor progression. However, its significance in hepatocellular carcinoma (HCC) is not well established.

Methods

We analyzed tissue specimens from healthy liver (n = 36), cirrhotic liver (n = 24), and HCC (n = 60) by immunohistochemistry, using antibody D2-40 specific for lymphendothelia. We subsequently quantified lymphatic microvessel density (LVD). The LVD was correlated with clinicopathological characteristics of the tumors as well as survival and disease-free survival of the patients.

Results

In contrast to healthy as well as cirrhotic liver, lymphangiogenesis was induced in HCC. Lymphatic vessels were detected in the intratumoral septa as well as within the bulk of tumor cells. Tumors with high LVD (24 of 60) had developed significantly more frequently in cirrhotic livers (P = 0.001) and were more frequently restricted to one liver lobe (P = 0.04). Univariate analysis revealed high LVD as a marker for reduced survival and disease-free survival disadvantage (median >60 vs. 21 months, P = 0.018, and 19 vs. 8 months, P = 0.047, respectively). In multivariate analysis, LVD showed a trend toward association with reduced survival (P = 0.059) and represented an independent prognostic factor for disease-free survival (P = 0.017).

Conclusions

Tumor-associated lymphangiogenesis is involved in neovascularization of hepatocellular carcinoma. Quantitative analysis of LVD demonstrated a significant influence of lymphangiogenesis on survival and established LVD as an independent predictor of disease-free survival. Quantification of LVD may be helpful in identifying patients with a high risk of tumor recurrence.

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Acknowledgment

A.S. was supported by a grant from the Deutsche Forschungsgemeinschaft.

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Authors and Affiliations

  1. Department of Visceral, Transplantation, Thoracic and Vascular Surgery, University of Leipzig, Liebigstrasse 20, 04103, Leipzig, Germany

    Armin Thelen MD, Sven Jonas MD, PhD, Christoph Benckert MD & Christian Bötcher MD

  2. Department of Pathology, Charité Campus Mitte, Charité Universitaetsmedizin Berlin, Berlin, Germany

    Wilko Weichert MD

  3. Department of Hepatology, Gastroenterology, Endocrinology and Metabolism, Campus Virchow-Klinikum, Charité Universitaetsmedizin Berlin, Berlin, Germany

    Eckart Schott MD, PhD, Bertram Wiedenmann MD, PhD & Arne Scholz MD

  4. Institute of Biometry and Clinical Epidemiology, Charité Campus Mitte, Charité Universitaetsmedizin Berlin, Berlin, Germany

    Ekkehart Dietz MD

  5. Department of General, Visceral and Transplantation Surgery, Campus Virchow-Klinikum, Charité Universitaetsmedizin Berlin, Berlin, Germany

    Peter Neuhaus MD, PhD

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  1. Armin Thelen MD
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  2. Sven Jonas MD, PhD
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Correspondence to Armin Thelen MD.

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Thelen, A., Jonas, S., Benckert, C. et al. Tumor-Associated Lymphangiogenesis Correlates with Prognosis after Resection of Human Hepatocellular Carcinoma. Ann Surg Oncol 16, 1222–1230 (2009). https://doi.org/10.1245/s10434-009-0380-1

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  • DOI: https://doi.org/10.1245/s10434-009-0380-1

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