[Significance and mechanisms of overexpression of PAK1 gene in epithelial ovarian neoplasms].
OBJECTIVE
To investigate the significance and mechanisms of overexpression of p21-activated kinase 1 gene (PAK1) in epithelial ovarian neoplasms.


METHODS
Immunohistochemistry, fluorescence in situ hybridization and terminal deoxynucleotidyl transferase-mediated dUTP nick end-labeling methods were used to examine the protein expression and amplification of PAK1 and cell apoptosis in 30 benign ovarian adenomas, 20 borderline tumors and 80 ovarian carcinomas by tissue microarray.


RESULTS
In immunohistochemistry study, overexpression of PAK1 protein was observed in 7 (25.9%) informative benign ovarian adenomas, 7 (36.8%) borderline tumors and 53 (68.8%) ovarian carcinomas. A significant inverse correlation of PAK1 overexpression and cell apoptosis was observed in these epithelial ovarian neoplasm cohorts (P = 0.002). In addition, 27/31 (87.1%) poorly differentiated (G3) carcinomas showed overexpression of PAK1, the frequency was significantly higher than that in tumors of G1 - G2 (26/46, 56.5% , P =0.01). In fluorescence in situ hybridization study, only 2 (4.7%) informative ovarian carcinomas showed amplification of PAK1 gene. None of the borderline and benign ovarian tumors showed PAK1 amplification.


CONCLUSIONS
Overexpression of PAK1 protein may be involved in the tumorigenesis of epithelial ovarian neoplasms and it is associated closely with the malignant histological phenotype of ovarian carcinomas. Mechanism other than gene amplification of PAK1 may play a more important role in the regulation of protein expression of PAK1 in ovarian tumors.
Xie
Dan
D
State Key Laboratory of Oncology in Southern China, Caner Center, Sun Yat-Sen University, Guangzhou 510060, China. danxie@graduate.hku.hk
Yang
Guo-Feng
GF
Chen
Yu-Qing
YQ
Jiang
Lin-Fang
LF
Xiao
Liu-Zhen
LZ
D000236:Adenoma / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D017209:Apoptosis; D018282:Cystadenocarcinoma, Mucinous / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D018284:Cystadenocarcinoma, Serous / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D005260:Female; D005784:Gene Amplification; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D007150:Immunohistochemistry; D017404:In Situ Hybridization, Fluorescence; D020287:In Situ Nick-End Labeling; D008875:Middle Aged; D009367:Neoplasm Staging; D010051:Ovarian Neoplasms / Q000235:genetics / Q000378:metabolism / Q000473:pathology*; D054462:p21-Activated Kinases / Q000235:genetics / Q000378:metabolism*
C515903:PAK1 protein, human; D054462:p21-Activated Kinases