title: Relationship between pancreatic secretory trypsin inhibitor and early recurrence of intrahepatic cholangiocarcinoma following surgical resection.
abstract: OBJECTIVE
  The extremely unfavorable prognosis of intrahepatic cholangiocarcinoma (ICC), even after surgical resection, is mainly attributed to a high rate of recurrence. The aim of this study was to identify the molecules associated with early recurrence of ICC following resection.
  
  
  METHODS
  Between December 1984 and July 2003, 46 patients with ICC underwent surgical resection. The clinical outcome of these patients was evaluated in view of the time of recurrence. Consequently, we categorized ICC patients into subgroups, based on the clinical results, and screened differentially expressed genes by DNA microarray analysis. Furthermore, the obtained results were validated in an independent sample set by quantitative real-time reverse transcription-polymerase chain reaction (RT-PCR). Immunohistochemistry was performed to assess the expressed genes at the protein level.
  
  
  RESULTS
  The survival of patients with early recurrence, occurring within a year after surgical resection, was significantly poor after surgery and even after recurrence, as compared to that of patients whose recurrence occurred beyond a year after surgery. By the DNA microarray analysis, 13 differentially expressed genes were picked up, and quantitative RT-PCR reaction identified the pancreatic secretory trypsin inhibitor (PSTI) as a candidate gene associated with early recurrence of ICC after resection. This observation was confirmed through examination of an independent set of samples, in which the patients with higher levels of PSTI mRNA expression had significantly shorter recurrence-free survival. Immunohistochemically, PSTI was expressed in the cytoplasm of cancer cells.
  
  
  CONCLUSIONS
  PSTI might be a potential marker for identifying ICC patients with an increased risk of early recurrence after surgical resection.
authors.affiliation: Department of General Surgery, Graduate School of Medicine, Chiba University, Chiba, Japan.
authors.forename: Akihiko
authors.initials: A
authors.lastname: Tonouchi
authors.forename: Masayuki
authors.initials: M
authors.lastname: Ohtsuka
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Ito
authors.forename: Fumio
authors.initials: F
authors.lastname: Kimura
authors.forename: Hiroaki
authors.initials: H
authors.lastname: Shimizu
authors.forename: Masaki
authors.initials: M
authors.lastname: Kato
authors.forename: Yoshinori
authors.initials: Y
authors.lastname: Nimura
authors.forename: Katsuro
authors.initials: K
authors.lastname: Iwase
authors.forename: Takaki
authors.initials: T
authors.lastname: Hiwasa
authors.forename: Naohiko
authors.initials: N
authors.lastname: Seki
authors.forename: Masaki
authors.initials: M
authors.lastname: Takiguchi
authors.forename: Masaru
authors.initials: M
authors.lastname: Miyazaki
mesh_terms: D000368:Aged; D001650:Bile Duct Neoplasms / Q000235:genetics / Q000473:pathology* / Q000601:surgery; D001653:Bile Ducts, Intrahepatic; D014408:Biomarkers, Tumor / Q000235:genetics; D018281:Cholangiocarcinoma / Q000235:genetics / Q000473:pathology* / Q000601:surgery; D005260:Female; D006801:Humans; D008297:Male; D009364:Neoplasm Recurrence, Local; D020411:Oligonucleotide Array Sequence Analysis; D011237:Predictive Value of Tests; D011379:Prognosis; D020133:Reverse Transcriptase Polymerase Chain Reaction; D014359:Trypsin Inhibitor, Kazal Pancreatic / Q000235:genetics* / Q000378:metabolism
chemical_list: D014408:Biomarkers, Tumor; D014359:Trypsin Inhibitor, Kazal Pancreatic