Skp2 overexpression is a prognostic factor in patients with ovarian adenocarcinoma.
OBJECTIVE
The purpose of this study was to examine Skp2 expression in epithelial ovarian tumors and to identify the association of Skp2 expression levels with patient survival.


METHODS
Skp2 protein expression was examined by immunohistochemistry in 134 epithelial ovarian tumors [20 adenomas, 23 low malignant potential (LMP) tumors, and 91 adenocarcinomas]. Results of immunostaining were correlated with clinicopathological variables and overall survival. Skp2 mRNA expression was examined by semiquantitative PCR in 32 ovarian adenocarcinomas and in 3 ovarian cancer cell lines.


RESULTS
Skp2 expression was detected in neither ovarian adenomas nor LMP tumors. In contrast, Skp2 expression was detected in 47.3% (43 of 91) of adenocarcinomas. Positive Skp2 expression was detected significantly more often in adenocarcinomas than in LMP tumors (P < 0.0001) or in adenomas (P < 0.0001). A significantly higher detection rate of Skp2 expression was observed in advanced-stage diseases compared with early-stage diseases (P = 0.010). Log-rank testing showed that Skp2 overexpression was significantly correlated with poor patient survival (P = 0.0035). Older age (P = 0.0026), advanced clinical stage (P < 0.0001), and high histological grades of the tumors (P = 0.0018) were also significantly associated with poor prognoses. In multivariate analysis, Skp2 overexpression (P = 0.0069) and clinical stage (P < 0.0001) remained significantly associated with overall survival, whereas age and histological grade lost their significance. Considerable levels of Skp2 mRNA expression were detected in all ovarian adenocarcinomas examined by semiquantitative PCR.


CONCLUSIONS
Skp2 expression might play an important role in the development and progression of ovarian adenocarcinomas, and Skp2 overexpression is an independent prognostic marker of ovarian adenocarcinoma patients.
Department of Obstetrics and Gynecology, Hiroshima University Graduate School of Biomedical Sciences, Japan. kazu@hiroshima-u.ac.jp
Kazushi
K
Shigemasa
Lijun
L
Gu
Timothy J
TJ
O'Brien
Koso
K
Ohama
D000230:Adenocarcinoma / Q000378:metabolism* / Q000473:pathology; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D005260:Female; D006801:Humans; D007124:Immunoenzyme Techniques; D008875:Middle Aged; D009363:Neoplasm Proteins / Q000235:genetics / Q000378:metabolism*; D010051:Ovarian Neoplasms / Q000378:metabolism* / Q000473:pathology; D016133:Polymerase Chain Reaction; D011379:Prognosis; D012333:RNA, Messenger / Q000378:metabolism; D012334:RNA, Neoplasm / Q000235:genetics / Q000378:metabolism; D044786:S-Phase Kinase-Associated Proteins / Q000235:genetics / Q000378:metabolism*; D015996:Survival Rate; D014407:Tumor Cells, Cultured
D009363:Neoplasm Proteins; D012333:RNA, Messenger; D012334:RNA, Neoplasm; D044786:S-Phase Kinase-Associated Proteins