Oncogenic role of clusterin overexpression in multistage colorectal tumorigenesis and progression.
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.
Xie
Dan
D
Department of Clinical Oncology, The University of Hong Kong, Room 109, School of Chinese Medicine Building, 10 Sassoon Road, Hong Kong, China.
Sham
Jonathan-S-T
JS
Zeng
Wei-Fen
WF
Che
Li-Hong
LH
Zhang
Meng
M
Wu
Hui-Xi
HX
Lin
Han-Liang
HL
Wen
Jian-Ming
JM
Lau
Sze-Hang
SH
Hu
Liang
L
Guan
Xin-Yuan
XY
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
C495242:CLU protein, human; D051152:Clusterin; D006023:Glycoproteins; D018832:Molecular Chaperones