Up-regulated expression of cytoplasmic clusterin in human ovarian carcinoma.
BACKGROUND
Recently, tumorigenic roles of the clusterin gene in several human malignancies have been suggested, but its potential role in the development and progression of ovarian carcinoma is unclear.


METHODS
In the current study, immunohistochemistry was used to examine the expression status of clusterin in 10 normal ovaries, 20 ovarian cystadenomas, 15 borderline ovarian tumors, and 240 ovarian carcinomas (nonmetastatic and metastatic) by tissue microarray. In addition, the apoptotic index of each tumor was assessed with a terminal deoxyuridine triphosphate nick-end labeling assay.


RESULTS
Positive staining for clusterin in different ovarian tissues was observed primarily a cytoplasmic pattern. Cytoplasmic overexpression of clusterin was detected in none of the normal ovaries, in 17% of cystadenomas, in 38% of borderline tumors, and in 58% of invasive ovarian carcinomas. A significant association was observed (P < 0.001) between the overexpression of clusterin and late clinical stage according to the International Federation of Gynecology and Obstetrics staging system. In addition, the overexpression of clusterin was detected more frequently in metastatic lesions than that in their matched primary tumors. The current results also provided evidence that the overexpression of cytoplasmic clusterin in carcinomas was correlated inversely with the tumors' apoptotic index, demonstrating an antiapoptotic function of cytoplasmic clusterin in ovarian carcinomas.


CONCLUSIONS
The current results suggested that the overexpression of cytoplasmic clusterin may represent an acquired malignant phenotypic feature of ovarian carcinoma and may be one of the important factors in determining the aggressive nature of ovarian carcinoma.
Xie
Dan
D
Department of Pathology, Zhong Shan Medical College, Sun Yat-Sen University, Guangzhou, China.
Lau
Sze Hang
SH
Sham
Jonathan S T
JS
Wu
Qiu-Liang
QL
Fang
Yan
Y
Liang
Li-Zhi
LZ
Che
Li-Hong
LH
Zeng
Yi-Xin
YX
Guan
Xin-Yuan
XY
D000328:Adult; D000368:Aged; D014408:Biomarkers, Tumor / Q000032:analysis*; D001707:Biopsy, Needle; D002277:Carcinoma / Q000235:genetics / Q000473:pathology*; D016022:Case-Control Studies; D016009:Chi-Square Distribution; D051152:Clusterin; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D006023:Glycoproteins / Q000235:genetics / Q000378:metabolism*; D006801:Humans; D007150:Immunohistochemistry; D020287:In Situ Nick-End Labeling; D008875:Middle Aged; D018832:Molecular Chaperones / Q000235:genetics / Q000378:metabolism*; D009367:Neoplasm Staging; D010051:Ovarian Neoplasms / Q000235:genetics / Q000473:pathology*; D011336:Probability; D011379:Prognosis; D012016:Reference Values; D012680:Sensitivity and Specificity; D015854:Up-Regulation
D014408:Biomarkers, Tumor; C495242:CLU protein, human; D051152:Clusterin; D006023:Glycoproteins; D018832:Molecular Chaperones