title: Oncogenic role of clusterin overexpression in multistage colorectal tumorigenesis and progression.
abstract: OBJECTIVE
  To investigate the expression pattern of clusterin in colorectal adenoma-carcinoma-metastasis series, and to explore the potential role of clusterin in multistage colorectal tumorigenesis and progression.
  
  
  METHODS
  A colorectal carcinoma (CRC)-tissue microarray (TMA), which contained 85 advanced CRCs including 43 cases of Dukes B, 21 of Dukes C and 21 of Dukes D tumors, were used for assessing the expression of clusterin (clone 41D) and tumor cell apoptotic index (AI) by immunohistochemistry and TUNEL assay, respectively. Moreover the potential correlation of clusterin expression with the patient's clinical-pathological features were also examined.
  
  
  RESULTS
  The positive staining of clusterin in different colorectal tissues was primarily a cytoplasmic pattern. Cytoplasmic overexpression of clusterin was detected in none of the normal colorectal mucosa, 17% of the adenomas, 46% of the primary CRCs, and 57% of the CRC metastatic lesions. In addition, a significant positive correlation between overexpression of clusterin and advanced clinical (Dukes) stage was observed (P<0.01). Overexpression of cytoplasmic clusterin in CRCs was inversely correlated with tumor apoptotic index (P<0.01), indicating the anti-apoptotic function of cytoplasmic clusterin in CRCs.
  
  
  CONCLUSIONS
  These data suggests that overexpression of cytoplasmic clusterin might be involved in the tumorigenesis and/or progression of CRCs. The anti-apoptotic function of cytoplasmic clusterin may be responsible, at least in part, for the development and biologically aggressive behavior of CRC.
authors.affiliation: Department of Clinical Oncology, The University of Hong Kong, Room 109, School of Chinese Medicine Building, 10 Sassoon Road, Hong Kong, China.
authors.forename: Dan
authors.initials: D
authors.lastname: Xie
authors.forename: Jonathan-S-T
authors.initials: JS
authors.lastname: Sham
authors.forename: Wei-Fen
authors.initials: WF
authors.lastname: Zeng
authors.forename: Li-Hong
authors.initials: LH
authors.lastname: Che
authors.forename: Meng
authors.initials: M
authors.lastname: Zhang
authors.forename: Hui-Xi
authors.initials: HX
authors.lastname: Wu
authors.forename: Han-Liang
authors.initials: HL
authors.lastname: Lin
authors.forename: Jian-Ming
authors.initials: JM
authors.lastname: Wen
authors.forename: Sze-Hang
authors.initials: SH
authors.lastname: Lau
authors.forename: Liang
authors.initials: L
authors.lastname: Hu
authors.forename: Xin-Yuan
authors.initials: XY
authors.lastname: Guan
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D017209:Apoptosis; D051152:Clusterin; D015179:Colorectal Neoplasms / Q000235:genetics* / Q000473:pathology* / Q000503:physiopathology; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D006023:Glycoproteins / Q000235:genetics*; D006801:Humans; D008297:Male; D008875:Middle Aged; D018832:Molecular Chaperones / Q000235:genetics*; D009367:Neoplasm Staging
chemical_list: C495242:CLU protein, human; D051152:Clusterin; D006023:Glycoproteins; D018832:Molecular Chaperones