title: The presence of tumor-infiltrating IL-17-producing cells in juvenile nasopharyngeal angiofibroma tumor microenvironment is a poor prognostic factor.
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.
  
  
  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.
  
  
  CONCLUSIONS
  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.
authors.affiliation: Department of Otolaryngology, Eye, Ear, Nose and Throat Hospital, Shanghai Medical College, Fudan University, Shanghai, China.
authors.forename: Xicai
authors.initials: X
authors.lastname: Sun
authors.affiliation: Department of Otolaryngology, Eye, Ear, Nose and Throat Hospital, Shanghai Medical College, Fudan University, Shanghai, China.
authors.forename: Limin
authors.initials: L
authors.lastname: Guo
authors.affiliation: Department of Otolaryngology, Eye, Ear, Nose and Throat Hospital, Shanghai Medical College, Fudan University, Shanghai, China.
authors.forename: Huan
authors.initials: H
authors.lastname: Wang
authors.affiliation: Department of Otolaryngology, Eye, Ear, Nose and Throat Hospital, Shanghai Medical College, Fudan University, Shanghai, China.
authors.forename: Huapeng
authors.initials: H
authors.lastname: Yu
authors.affiliation: Department of Otolaryngology, Eye, Ear, Nose and Throat Hospital, Shanghai Medical College, Fudan University, Shanghai, China.
authors.forename: Jingjing
authors.initials: J
authors.lastname: Wang
authors.affiliation: Department of Otolaryngology, Eye, Ear, Nose and Throat Hospital, Shanghai Medical College, Fudan University, Shanghai, China.
authors.forename: Xinjun
authors.initials: X
authors.lastname: Meng
authors.affiliation: Department of Otolaryngology, Eye, Ear, Nose and Throat Hospital, Shanghai Medical College, Fudan University, Shanghai, China.
authors.forename: Zhuofu
authors.initials: Z
authors.lastname: Liu
authors.affiliation: Department of Otolaryngology, Eye, Ear, Nose and Throat Hospital, Shanghai Medical College, Fudan University, Shanghai, China.
authors.forename: Juan
authors.initials: J
authors.lastname: Liu
authors.affiliation: Department of Otolaryngology, Eye, Ear, Nose and Throat Hospital, Shanghai Medical College, Fudan University, Shanghai, China.
authors.forename: Li
authors.initials: L
authors.lastname: Hu
authors.affiliation: Department of Otolaryngology, Eye, Ear, Nose and Throat Hospital, Shanghai Medical College, Fudan University, Shanghai, China.
authors.forename: Han
authors.initials: H
authors.lastname: Li
authors.affiliation: Department of Otolaryngology, Eye, Ear, Nose and Throat Hospital, Shanghai Medical College, Fudan University, Shanghai, China. Electronic address: wangdehuient@sina.com.
authors.forename: Dehui
authors.initials: D
authors.lastname: Wang
mesh_terms: D000293:Adolescent; D000328:Adult; D000367:Age Factors; D018322:Angiofibroma / Q000378:metabolism* / Q000473:pathology; D016022:Case-Control Studies; D005260:Female; D006801:Humans; D007124:Immunoenzyme Techniques; D020381:Interleukin-17 / Q000378:metabolism*; D008297:Male; D009303:Nasopharyngeal Neoplasms / Q000378:metabolism* / Q000473:pathology; D009364:Neoplasm Recurrence, Local; D009367:Neoplasm Staging; D011379:Prognosis; D015996:Survival Rate; D058504:Th17 Cells / Q000378:metabolism*; D046888:Tissue Array Analysis; D059016:Tumor Microenvironment
chemical_list: D020381:Interleukin-17