Lymphangiogenesis and biological behavior in pancreatic carcinoma and other pancreatic tumors

Abstract

Lymphatic vessels in primary tumor tissue play an important role in lymphatic metastasis. Lymphatic metastasis of malignant neoplasms is significantly related to prognosis, influencing both recurrence and survival. The aim of this study was to investigate the correlation of intra-tumoral lymphatic vessel density (iLVD) and peri-tumoral lymphatic vessel density (pLVD) with biological behavior and prognostic parameters in pancreatic carcinoma (PC) and other pancreatic tumors. Lymphangiogenesis was examined using the D2-40 monoclonal antibody in 33 cases of PC, 7 neuroendocrine tumors of the pancreas (NETP), 7 solid pseudopapillary tumors of the pancreas (SPTP) and 3 cystadenomas of the pancreas (CP). Positively-stained microvessels were counted at magnification ×400 in dense lymphatic vascular foci (hotspots). The LVD of PC was compared to 3 other pancreatic tumors. The relationships among the LVD, the extent of differentiation, lymphatic invasion, lymph node metastasis and other clinicopathological parameters of PC were analyzed. There was no difference in the iLVD among PC, NETP, SPTP and CP. The pLVD of NETP was markedly higher than that of PC, SPTP and CP. The pLVD of PC was significantly higher than that of SPTP and CP, but there was no difference between SPTP and CP. The pLVD of PC was significantly associated with the extent of differentiation, lymphatic invasion and lymph node metastasis, whereas it was not associated with age, gender, tumor size, tumor location and peri-pancreatic invasion. The iLVD of PC was not correlated with these clinicopathological parameters. There was no difference in iLVD and no marked difference in pLVD among the pancreatic tumors. Detection of pLVD is of greater importance than detecting iLVD in these pancreatic tumors, as pLVD can be utilized for the prediction of lymph node metastasis, thus aiding in the evaluation of patient prognosis.

The relationship between lymphatic vascular density and vascular endothelial growth factor A (VEGF-A) expression with clinical-pathological features and survival in pancreatic adenocarcinomas

“…Furthermore, the formation of new lymph vessels is an early process that develops before tumorigenesis, and as the tumor grows, the lymph vessels are inhibited or disabled. Our study also reports the same prognostic importance of LVD that was found by Wang et al [ 38 ].…”

Combined targeting of TGF-β, EGFR and HER2 suppresses lymphangiogenesis and metastasis in a pancreatic cancer model

“…However, some studies suggest that intratumoral lymphatic vessel density (LVD) is not associated with lymphatic invasion or metastasis [11, 54]. Moreover, LVD is heterogeneous and PDACs can have collapsed lymphatic vessels which may interfere with cancer cell infiltration of lymph nodes [15, 54]. Nevertheless, some patients develop lymphatic metastases in the absence of robust lymphangiogenesis [11].…”

The lymphatic system and pancreatic cancer

“…They also showed increased LVD within metastatic lymph nodes [154]. Wang, et al , found that increased peritumoral LVD in human pancreatic carcinoma tissues correlated with unfavorable tumor differentiation status, increased LVI, and more lymph node metastasis, while this was not the case for intratumoral LVD [53]. These data highlight the importance of peripancreatic lymphatics in the progression and metastasis of pancreatic cancer and their potential utility as both a predictor of patient outcomes and a possible therapeutic target.…”

“…However, the prognostic value of mode of lymph node invasion is arguable: some studies report poorer overall survival in patients with lymphatic vessel-directed metastasis as compared to direct invasion [178], while other reports show no survival difference between the two modes of lymph node invasion [109,177]. Although lymph node invasion by PDAC occurs most frequently through the lymphatic vasculature, the LVD at the tumor site has not been conclusively correlated with either lymph node metastasis or prognosis due to conflicting study results [53,156,162,179]. This is also true for studies examining the expression of pro-lymphangiogenic factors such as VEGF-C and -D [162,180,181] (and in pancreatic endocrine tumors [182]).…”