title: Nuclear expression of thioredoxin-1 in the invasion front is associated with outcome in patients with gallbladder carcinoma.
abstract: BACKGROUND
  Multifunctional redox protein human thioredoxin (TRX-1) is reduced by thioredoxin reductase (TRX-R). The aim of the present study was to examine the distribution of TRX-1 and TRX-R expressions in gallbladder carcinoma (GBC) to clarify their usefulness as prognostic factors after surgical resection.
  
  
  METHODS
  Immunohistochemical staining for TRX-1 and TRX-R was performed in GBC tissue from 38 patients who underwent surgical resection, and TRX-1/TRX-R localization in relation to outcome was examined.
  
  
  RESULTS
  TRX-1 protein levels were significantly higher in GBC samples than in cholecystolithiasis samples (P = 0.0174). TRX-1 expression was observed in 100% (38/38) of tumour samples and in the nucleus in 76% (29/38), with nuclear expression in the invasion front observed in 45% (13/29). TRX-R expression was only detected in the cytoplasm of cancer cells and in the invasion front in 28 samples. In all of the samples, the depth of tumour invasion, lymph node metastasis, surgical margin, curability and nuclear expression of TRX-1 in the invasion front were significant prognostic factors by univariate analysis. In 27 selected patients who underwent curative resection, both TRX-1 nuclear expression and TRX-R cytoplasmic expression in the invasion front was a significantly prognostic factor.
  
  
  CONCLUSIONS
  TRX-1 nuclear expression in the GBC invasion front is a significant prognostic marker. Patients with both TRX-1 nuclear expression and TRX-R cytoplasmic expression in the tumour invasion front should be observed carefully even if after curative resection.
authors.affiliation: Department of Surgical Oncology and Regulation of Organ Function, Miyazaki University School of Medicine, Kiyotake, Miyazaki, Japan.
authors.forename: Motoaki
authors.initials: M
authors.lastname: Nagano
authors.forename: Kinta
authors.initials: K
authors.lastname: Hatakeyama
authors.forename: Masahiro
authors.initials: M
authors.lastname: Kai
authors.forename: Hajime
authors.initials: H
authors.lastname: Nakamura
authors.forename: Junji
authors.initials: J
authors.lastname: Yodoi
authors.forename: Yujiro
authors.initials: Y
authors.lastname: Asada
authors.forename: Kazuo
authors.initials: K
authors.lastname: Chijiiwa
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D014408:Biomarkers, Tumor / Q000032:analysis*; D015153:Blotting, Western; D002277:Carcinoma / Q000737:chemistry* / Q000401:mortality / Q000556:secondary / Q000601:surgery; D002467:Cell Nucleus / Q000737:chemistry*; D003593:Cytoplasm / Q000737:chemistry; D005260:Female; D005706:Gallbladder Neoplasms / Q000737:chemistry* / Q000401:mortality / Q000473:pathology / Q000601:surgery; D006801:Humans; D007150:Immunohistochemistry; D007564:Japan; D053208:Kaplan-Meier Estimate; D008207:Lymphatic Metastasis; D008297:Male; D008875:Middle Aged; D009361:Neoplasm Invasiveness; D009367:Neoplasm Staging; D013880:Thioredoxin-Disulfide Reductase / Q000032:analysis; D013879:Thioredoxins / Q000032:analysis*; D016896:Treatment Outcome; D015854:Up-Regulation
chemical_list: D014408:Biomarkers, Tumor; C491203:TXN protein, human; D013879:Thioredoxins; D013880:Thioredoxin-Disulfide Reductase