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

Abstract

BackgroundPancreatic cancer is a rare tumor with an extremely low survival rate. Its known risk factors include the chronic use of tobacco and excessive alcohol consumption and the presence of chronic inflammatory diseases, such as pancreatitis and type 2 diabetes. Angiogenesis and lymphangiogenesis, which have been the focus of recent research, are considered prognostic factors for cancer development. Knowing the angiogenic and lymphangiogenic profiles of a tumor may provide new insights for designing treatments according to the different properties of the tumor. The aim of this study was to evaluate the density of blood and lymphatic vessels, and the expression of VEGF-A, in pancreatic adenocarcinomas, as well as the relationship between blood and lymphatic vascular density and the prognostically important clinical-pathological features of pancreatic tumors.MethodsParaffin blocks containing tumor samples from 100 patients who were diagnosed with pancreatic cancer between 1990 and 2010 were used to construct a tissue microarray. VEGF expression was assessed in these samples by immunohistochemistry. To assess the lymphatic and vascular properties of the tumors, 63 cases that contained sufficient material were sectioned routinely. The sections were then stained with the D2-40 antibody to identify the lymphatic vessels and with a CD34 antibody to identify the blood vessels. The vessels were counted individually with the Leica Application Suite v4 program. All statistical analyses were performed using SPSS 18.0 (Chicago, IL, USA) software, and p values ≤ 0.05 were considered significant.ResultsIn the Cox regression analysis, advanced age (p=0.03) and a history of type 2 diabetes (p=0.014) or chronic pancreatitis (p=0.02) were shown to be prognostic factors for pancreatic cancer. Blood vessel density (BVD) had no relationship with clinical-pathological features or death. Lymphatic vessel density (LVD) was inversely correlated with death (p=0.002), and by Kaplan-Meyer survival analysis, we found a significant association between low LVD (p=0.021), VEGF expression (p=0.023) and low patient survival.ConclusionsPancreatic carcinogenesis is related to a history of chronic inflammatory processes, such as type 2 diabetes and chronic pancreatitis. In pancreatic cancer development, lymphangiogenesis can be considered an early event that enables the dissemination of metastases. VEGF expression and low LVD can be considered as poor prognostic factors as tumors with this profile are fast growing and highly aggressive.Virtual slidesThe virtual slide(s) for this article can be found here: http://www.diagnosticpathology.diagnomx.eu/vs/5113892881028514

Expression of cluster of differentiation 34 and vascular endothelial growth factor in breast cancer, and their prognostic significance

“…However, the administration of bevacizumab combined with paclitaxel for the treatment of metastatic breast cancer is still retained in the American National Comprehensive Cancer Network Guide (26). In addition, it is still widely applied in the treatment of colon cancer, lung cancer, glioblastoma, renal cell carcinoma and other tumors (4,27).…”

VEGF expression in pancreatic cancer and other malignancies: a review of the literature

“…The lymphangiogenesis can be considered an early event that enables the dissemination of metastases. VEGF expression and low lymphatic vessel density can be considered as poor prognostic factors as tumors with this profile are fast growing and highly aggressive [76]. VEG Foverexpression was found to be associated with high microvascular density and emerged as adverse prognostic factors in terms of patient survival in pancreatic ductal adenocarcinoma [77].…”

The lymphatic system and pancreatic cancer

“…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]).…”