title: Differential expression of basement membrane type IV collagen α2 and α6 chains as a prognostic factor in patients with extrahepatic bile duct carcinoma.
abstract: BACKGROUND
  The destruction of the basement membrane (BM) is the first step in cancer invasion and metastasis. Type IV collagen is a major component of the BM, and is composed of six genetically distinct α(IV) chains; α1(IV) to α6(IV). The loss of α5(IV) and α6(IV) chains from the epithelial BM at the early stage of cancer invasion has been reported in several types of cancers. However, the expression of α5(IV) and α6(IV) chains in extrahepatic bile duct carcinoma (EBDC) remains unclear.
  
  
  METHODS
  We examined the expression of α(IV) chains by immunohistochemistry using 71 resected EBDC specimens. Prognostic significance of α(IV) chains was examined by Cox regression and Kaplan-Meier analyses.
  
  
  RESULTS
  In the invasive cancer, the expression of α6(IV) chain in the BM was lost partially or completely preceded by the loss of α2(IV) chain. The loss of α6(IV) chain in the BM of the invasive cancer was related to the tumor classification, TNM stages, and the expression of α2(IV) chain. The patients with α2(IV)-negative and α6(IV)-negative chains had significantly poorer prognosis than those with α2(IV)-positive and α6(IV)-positive/negative chains (P = 0.04).
  
  
  CONCLUSIONS
  The loss of α2(IV) and α6(IV) chains might be a useful prognostic factor in patients with EBDC.
authors.affiliation: Department of Gastroenterological Surgery, Graduate School of Medical Sciences, Kumamoto University, Kumamoto City, Kumamoto, Japan.
authors.forename: Kotaro
authors.initials: K
authors.lastname: Hirashima
authors.forename: Ken-Ichi
authors.initials: K
authors.lastname: Iyama
authors.forename: Yoshifumi
authors.initials: Y
authors.lastname: Baba
authors.forename: Yumi
authors.initials: Y
authors.lastname: Honda
authors.forename: Yoshikazu
authors.initials: Y
authors.lastname: Sado
authors.forename: Yoshifumi
authors.initials: Y
authors.lastname: Ninomiya
authors.forename: Masayuki
authors.initials: M
authors.lastname: Watanabe
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Takamori
authors.forename: Toru
authors.initials: T
authors.lastname: Beppu
authors.forename: Hideo
authors.initials: H
authors.lastname: Baba
mesh_terms: D000368:Aged; D000704:Analysis of Variance; D001485:Basement Membrane / Q000737:chemistry / Q000473:pathology; D001650:Bile Duct Neoplasms / Q000737:chemistry* / Q000473:pathology*; D017734:Bile Ducts, Extrahepatic / Q000737:chemistry / Q000473:pathology; D014408:Biomarkers, Tumor / Q000032:analysis*; D002277:Carcinoma / Q000737:chemistry* / Q000473:pathology*; D024141:Collagen Type IV / Q000032:analysis*; D015536:Down-Regulation; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D007150:Immunohistochemistry; D053208:Kaplan-Meier Estimate; D019394:Ki-67 Antigen / Q000032:analysis; D008207:Lymphatic Metastasis; D008297:Male; D008875:Middle Aged; D009361:Neoplasm Invasiveness; D009367:Neoplasm Staging; D011237:Predictive Value of Tests; D011379:Prognosis; D016016:Proportional Hazards Models; D016159:Tumor Suppressor Protein p53 / Q000032:analysis
chemical_list: D014408:Biomarkers, Tumor; C502625:COL4A2 protein, human; C559044:COL4A6 protein, human; D024141:Collagen Type IV; D019394:Ki-67 Antigen; D016159:Tumor Suppressor Protein p53