TY - JOUR
T1 - Tumor-associated lymphangiogenesis correlates with prognosis after resection of human hepatocellular carcinoma
AU - Thelen, Armin
AU - Jonas, Sven
AU - Benckert, Christoph
AU - Weichert, Wilko
AU - Schott, Eckart
AU - Bötcher, Christian
AU - Dietz, Ekkehart
AU - Wiedenmann, Bertram
AU - Neuhaus, Peter
AU - Scholz, Arne
N1 - Funding Information:
ACKNOWLEDGMENT A.S. was supported by a grant from the Deutsche Forschungsgemeinschaft.
PY - 2009/5
Y1 - 2009/5
N2 - 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.
AB - 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.
UR - http://www.scopus.com/inward/record.url?scp=64249103967&partnerID=8YFLogxK
U2 - 10.1245/s10434-009-0380-1
DO - 10.1245/s10434-009-0380-1
M3 - Article
C2 - 19224279
AN - SCOPUS:64249103967
SN - 1068-9265
VL - 16
SP - 1222
EP - 1230
JO - Annals of Surgical Oncology
JF - Annals of Surgical Oncology
IS - 5
ER -