Tumor-associated lymphangiogenesis correlates with prognosis after resection of human hepatocellular carcinoma

Armin Thelen, Sven Jonas, Christoph Benckert, Wilko Weichert, Eckart Schott, Christian Bötcher, Ekkehart Dietz, Bertram Wiedenmann, Peter Neuhaus, Arne Scholz

Research output: Contribution to journalArticlepeer-review

24 Scopus citations

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.

Original languageEnglish
Pages (from-to)1222-1230
Number of pages9
JournalAnnals of Surgical Oncology
Volume16
Issue number5
DOIs
StatePublished - May 2009
Externally publishedYes

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