title: C4.4A expression is associated with a poor prognosis of esophageal squamous cell carcinoma.
abstract: BACKGROUND
  C4.4A is a glycolipid-anchored membrane protein expressed in several human malignancies. We examined clinical relevance of C4.4A expression in 111 esophageal squamous cell carcinoma (ESCC) tissue samples.
  
  
  METHODS
  Anti-human C4.4A antibody that recognizes the glycosylphosphatidyl inositol (GPI) anchor signaling sequence (C4.4A-GPI Ab) and anti-human C4.4A-119 polyclonal antibody (C4.4A-119 Ab) were used for immunohistochemistry and Western blot testing.
  
  
  RESULTS
  Both antibodies detected the C4.4A protein expression at the parabasal layer of normal epithelium of the esophagus. In tumor tissues, the C4.4A protein was detected in 66 (59.5 %) and 95 (85.6 %) of 111 ESCCs by the C4.4A-GPI Ab and the C4.4A-119 Ab, respectively. The C4.4A-GPI Ab mainly detected membranous C4.4A expression (83.3 %, 55 of 66 positive cases), while the C4.4A-119 Ab exclusively detected cytoplasmic C4.4A expression (100 %, 73 cytoplasm alone and 22 cytoplasm plus membrane in 95 positive cases). Western blot analysis indicated that normal epithelium expressed the band of C4.4A at 70 kDa, whereas the tumor tissues displayed the band at the lower molecular weight. Survival analysis indicated that the C4.4A-positive ESCCs had significantly worse 5-year overall survival than the C4.4A-negative ESCC samples (P = 0.021) when using the C4.4A-GPI Ab, but not when using the C4.4A-119 Ab. This difference was most evident with membranous expression of C4.4A (P = 0.005).
  
  
  CONCLUSIONS
  C4.4A expression was associated with a poor prognosis of ESCC when the GPI-related antibody was used. On the other hand, the C4.4A-119 Ab may be a useful diagnostic tool for ESCC because of its high detection rate.
authors: Department of Gastroenterological Surgery, Graduated School of Medicine, Osaka University, Osaka, Japan.
authors: Masahisa
authors: M
authors: Ohtsuka
authors: Hirofumi
authors: H
authors: Yamamoto
authors: Toru
authors: T
authors: Masuzawa
authors: Hidekazu
authors: H
authors: Takahashi
authors: Mamoru
authors: M
authors: Uemura
authors: Naotsugu
authors: N
authors: Haraguchi
authors: Junichi
authors: J
authors: Nishimura
authors: Taishi
authors: T
authors: Hata
authors: Makoto
authors: M
authors: Yamasaki
authors: Hiroshi
authors: H
authors: Miyata
authors: Ichiro
authors: I
authors: Takemasa
authors: Tsunekazu
authors: T
authors: Mizushima
authors: Shuji
authors: S
authors: Takiguchi
authors: Yuichiro
authors: Y
authors: Doki
authors: Masaki
authors: M
authors: Mori
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D014408:Biomarkers, Tumor / Q000378:metabolism*; D002294:Carcinoma, Squamous Cell / Q000378:metabolism* / Q000556:secondary*; D015815:Cell Adhesion Molecules / Q000276:immunology / Q000378:metabolism*; D002462:Cell Membrane / Q000378:metabolism; D003593:Cytoplasm / Q000378:metabolism; D004938:Esophageal Neoplasms / Q000378:metabolism* / Q000473:pathology*; D005260:Female; D058851:GPI-Linked Proteins / Q000276:immunology / Q000378:metabolism; D017261:Glycosylphosphatidylinositols / Q000276:immunology; D006801:Humans; D007150:Immunohistochemistry; D053208:Kaplan-Meier Estimate; D008207:Lymphatic Metastasis; D008297:Male; D008875:Middle Aged; D015999:Multivariate Analysis; D009367:Neoplasm Staging; D011379:Prognosis
chemical_list: D014408:Biomarkers, Tumor; D015815:Cell Adhesion Molecules; D058851:GPI-Linked Proteins; D017261:Glycosylphosphatidylinositols; C472589:LYPD3 protein, human