title: Midkine promotes perineural invasion in human pancreatic cancer.
abstract: OBJECTIVE
  To investigate midkine (MK) and syndecan-3 protein expression in pancreatic cancer by immunohistochemistry, and to analyze their correlation with clinicopathological features, perineural invasion, and prognosis.
  
  
  METHODS
  Pancreatic cancer tissues (including adequately sized tumor tissue samples and tissue samples taken from areas less than 2.0 cm around the tumor) were taken from 42 patients who were undergoing a partial duodenopancreatectomy. MK and syndecan-3 proteins were detected by immunohistochemistry using a standardized streptavidin-peroxidase method, and analyzed for their correlation with clinicopathological features, perineural invasion, and prognosis. Associations of neural invasion with aggressive characteristics of pancreatic cancer and the presence of perineural invasion were assessed by two independent observers blinded to the patient status.
  
  
  RESULTS
  MK and syndecan-3 were found in 26 (61.9%) and 24 (57.1%) specimens, respectively. MK and syndecan-3 expression was associated with perineural invasion (P = 0.018 and 0.031, respectively). High MK expression was closely associated with advanced tumor, node and metastasis stage (P = 0.008), lymph node metastasis (P = 0.042), and decreased postoperative survival at 3 years (51.0% vs 21.8%, P = 0.001). Syndecan-3 levels were correlated with tumor size (P = 0.028). Patients who were syndecan-3 negative had a higher cumulative survival rate than those who were positive, but the difference was not significant (44.0% vs 23.0%, P > 0.05).
  
  
  CONCLUSIONS
  MK and syndecan-3 are frequently expressed in pancreatic cancer and associated with perineural invasion. High expression of MK and syndecan-3 may contribute to the highly perineural invasion and poor prognosis of human pancreatic cancer.
authors.affiliation: Jun Yao, Wen-Yao Li, Shuo-Guo Li, Xiao-Shan Feng, She-Gan Gao, Department of Oncology, First Affiliated Hospital, Henan University of Science and Technology, Luoyang 471003, Henan Province, China.
authors.forename: Jun
authors.initials: J
authors.lastname: Yao
authors.affiliation: Jun Yao, Wen-Yao Li, Shuo-Guo Li, Xiao-Shan Feng, She-Gan Gao, Department of Oncology, First Affiliated Hospital, Henan University of Science and Technology, Luoyang 471003, Henan Province, China.
authors.forename: Wen-Yao
authors.initials: WY
authors.lastname: Li
authors.affiliation: Jun Yao, Wen-Yao Li, Shuo-Guo Li, Xiao-Shan Feng, She-Gan Gao, Department of Oncology, First Affiliated Hospital, Henan University of Science and Technology, Luoyang 471003, Henan Province, China.
authors.forename: Shuo-Guo
authors.initials: SG
authors.lastname: Li
authors.affiliation: Jun Yao, Wen-Yao Li, Shuo-Guo Li, Xiao-Shan Feng, She-Gan Gao, Department of Oncology, First Affiliated Hospital, Henan University of Science and Technology, Luoyang 471003, Henan Province, China.
authors.forename: Xiao-Shan
authors.initials: XS
authors.lastname: Feng
authors.affiliation: Jun Yao, Wen-Yao Li, Shuo-Guo Li, Xiao-Shan Feng, She-Gan Gao, Department of Oncology, First Affiliated Hospital, Henan University of Science and Technology, Luoyang 471003, Henan Province, China.
authors.forename: She-Gan
authors.initials: SG
authors.lastname: Gao
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D021441:Carcinoma, Pancreatic Ductal / Q000378:metabolism / Q000401:mortality / Q000473:pathology*; D016022:Case-Control Studies; D002681:China / Q000453:epidemiology; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D000078792:Midkine; D009361:Neoplasm Invasiveness; D009414:Nerve Growth Factors / Q000378:metabolism*; D010179:Pancreas / Q000294:innervation / Q000473:pathology*; D010190:Pancreatic Neoplasms / Q000378:metabolism / Q000401:mortality / Q000473:pathology*; D053670:Syndecan-3 / Q000378:metabolism*
chemical_list: C066254:MDK protein, human; D009414:Nerve Growth Factors; C508301:SDC3 protein, human; D053670:Syndecan-3; D000078792:Midkine
keywords: Midkine; Neurite growth; Pancreatic cancer; Perineural invasion; Syndecan-3