Abstract
BackgroundTumor-associated lymphangiogenesis is considered significant in number of solid malignancies. However, its impact on prognosis of intrahepatic cholangiocarcinoma (ICC) after resection remains further confirmation. Herein, we conducted this study to evaluate prognostic impact of tumor-associated lymphangiogenesis in patients with ICC.MethodsExtent of tumor-associated lymphangiogenesis of ICC was evaluated by quantifying microlymphatic vessel density (MLVD) from immunohistochemical staining of a lymphatic endothelial-specific antibody (podoplanin). Clinicopathological characteristics were comprehensively analyzed to identify MLVD-associated factors. The patients were stratified into high and low MLVD groups according to the distinctive correlation between the MLVD and overall survival using the Spearman’s correlation test. Kaplan-Meier estimation was performed to confirm prognostic impact of MLVD in patients with ICC. Univariate and multivariate analyses were performed using the Cox proportional hazard model.ResultsThe MLVD between 4 to 12 counts showed inverse proportion to the overall survival (Spearman’s r = − 0.66; 95% confidence interval [CI], − 0.82 to − 0.39; p < 0.0001), which was set as a cut-off for the high MLVD group, whereas the MLVD between 13 to 25 showed no correlation to the overall survival (r = − 0.11; 95% CI, − 0.38 to 0.19; p = 0.4791). The high MLVD group showed more frequent lymph node metastasis (p < 0.001) and were more likely to suffer from recurrence of the tumor compared to the low MLVD group (p < 0.001). The high MLVD was found to be independently associated with reduced overall and recurrence-free survival. The 5-year overall survival of the patients with high MLVD was significantly lower compared to those with low MLVD (0% vs 48%).ConclusionsOur study reveals that tumor-associated lymphangiogenesis is significantly associated with increased lymphatic metastasis, recurrence of the tumor, and reduced overall survival in patients with ICC, thus providing guidance when estimating postresection prognosis.
Highlights
Tumor-associated lymphangiogenesis is considered significant in number of solid malignancies
Apart from that, lymphangiogenesis was found to be associated with increased frequency of tumor cells in lymphatics and lymph nodes in hilar cholangiocarcinoma [11]
We evaluated impact of tumor-associated lymphangiogenesis in patients with intrahepatic cholangiocarcinoma (ICC), a highly malignant and aggressive primary liver cancer
Summary
Tumor-associated lymphangiogenesis is considered significant in number of solid malignancies. Its impact on prognosis of intrahepatic cholangiocarcinoma (ICC) after resection remains further confirmation. In recent years, increasing experimental and clinicopathological studies indicated that lymphatic vessels undergo dynamic changes within the tumor, including tumor-associated lymphangiogenesis, that facilitate metastasis [7]. Specific signaling pathways, such as vascular endothelial growth factor C (VEGF-C) and its cognate receptor VEGF receptor 3 (VEGFR-3) are confirmed to stimulate tumor-associated lymphangiogenesis, as well as lymph node metastasis in experimental tumor models [8,9,10]. We evaluated impact of tumor-associated lymphangiogenesis in patients with ICC, a highly malignant and aggressive primary liver cancer
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