Abstract
Background
Although juvenile nasopharyngeal angiofibroma (JNA) is a benign tumor histologically, it demonstrates aggressive propensity of locally destructive growth causing bone erosion. The patients with JNA remain high recurrence rate after surgical excision. Th17 cells secrete the proinflammatory cytokine interleukin-17 (IL-17), and play an important role in carcinogenesis and tumor progression. So far, no studies have focused on the significance of IL-17-producing cells in the JNA tumor microenvironment. The current study was designed to investigate the localization and level of tumor-infiltrating IL-17-producing cells in JNA microenvironment. The presence and number of IL-17-producing cells were further analyzed for a possible association with clinicopathological features and disease outcome.
Materials and methods
Immunohistochemistry was used to analyze the expression of IL-17 in a tissue microarray from 70 patients with JNA and 10 control subjects. Correlations between the levels of IL-17 expression and clinicopathologic variables, as well as tumor recurrence, were assessed.
Results
In vessels, the IL-17-producing cells were identified in pericytes and irregular smooth muscle cells, but the matured vascular endothelial cells showed no IL-17 reactivity. The expression of IL-17 in stromal cells was concentrated in the less differentiated and plump cells that contained a central hypochromatic nucleus and single small nucleolus. Chi-square test showed that tumor stage (p = 0.09), operation history (p = 0.828), operation approach (p = 0.159), and volume of intraoperative hemorrhage (p = 0.352) were not associated with the expression of IL-17 in JNA patients. However, intratumoral IL-17-producing cells were negatively associated with patient’s age (p = 0.004). Furthermore, we found that patients with extensive infiltration of IL-17-producing cells had significantly higher recurrence rates than those with less infiltration of IL-17-producing cells (p = 0.028). Log rank analysis showed that JNA patients with high levels of IL-17 had significantly shorter disease free survival (DFS) than those with low levels of IL-17 (p = 0.004). Univariate Cox regression analysis suggested that IL-17 and patient’s age were significantly associated with DFS. Multivariate analysis indicated that high infiltration with IL-17-producing cells was associated with poor DFS. Of all clinicopathological features, IL-17 level was an independent factor predicting the patient’s prognosis.
Conclusion
In JNA patients, a high level of IL-17-producing cells was negatively associated with patient’s age. Patients with extensive infiltration of IL-17-producing cells had significantly higher tumor recurrence rates. High infiltration of IL-17-producing cells in JNA microenvironment is an independent poor prognostic factor for shorter disease-free survival. Future studies further focusing on the role of IL-17 may provide more promising therapeutic methods for extensive JNA tumors.
1
Introduction
Juvenile nasopharyngeal angiofibroma (JNA) is a rare, highly vascularized benign tumor originating from the superior margin of the sphenopalatine foramen or pterygoid canal . It accounts for approximately 0.05% of all head and neck tumors, and occurs almost exclusively in adolescent males. Although JNA is a benign tumor histologically, it has a propensity to grow destructively and erode bone. Surgery is the mainstay of treatment, but the recurrence rate after surgical excision of JNA is high and fairly heterogeneous, varying from 20% to over 50% .
Histopathology of JNA shows that it is composed of stromal cells and proliferating irregular vascular components. The typical stromal cells in JNA are fibroblasts in a dense collagen matrix . However, it has been found that JNA is also infiltrated by numerous inflammatory cells. Substantial evidence indicates that mast cells and T-lymphocytes are identified as major cellular populations in JNA as they represented 30% of the cells in studied tumor specimens . It has been shown that the inflammatory microenvironment plays a critical role in tumor progression . Tumor cells and host immune cells interact with each other to create the tumor microenvironment. CD4 + T cells are the major component of immune cells in the tumor microenvironment, and play an important role in tumor regression and evasion . CD4 + T helper 17 (Th17) cells have been identified as a novel subset of CD4 + T-lymphocytes, and are characterized by its signature cytokine interleukin-17 (IL-17). IL-17 is a pro-inflammatory cytokine, and has been implicated in inflammatory and autoimmune disease. Furthermore, several studies on skin cancer, hepatocellular carcinoma, gallbladder carcinoma, laryngeal, gastric, breast, colorectal, pancreatic and lung cancer have demonstrated that IL-17 exhibits tumor-promoting functions . However, in acute leukemia, advanced epithelial ovarian cancer and melanoma patients, the expression of IL-17 was reported to have an anti-tumor effect by promoting cytotoxic T-lymphocytes’ (CTL) activities, reducing angiogenesis and the recruitment of effector Th1 cells to the tumor . This contradictory result may be attributed to variant tumor immunogenicity and a different role of IL-17 in different tumor stages .
Recently, Wendler et al. showed that infiltration of JNA tumors by CD4 + and CD8 + T-lymphocytes was evident in immunofluorescent stainings . So far, no studies have focused on the significance of IL-17-producing cells in the JNA tumor microenvironment and the role of IL-17 in JNA remains unclear. Aim of the present study was to investigate the level of tumor-infiltrating IL-17-producing cells in JNA microenvironment, and analyze its association with clinicopathological features and disease outcome.
Stay updated, free articles. Join our Telegram channel
Full access? Get Clinical Tree
