Low-molecular weight forms of cyclin E differentiate ovarian carcinoma from cells of mesothelial origin and are associated with poor survival in ovarian carcinoma.
BACKGROUND
The authors recently reported on the role of cyclin E in differentiating ovarian/primary peritoneal carcinoma from malignant peritoneal mesothelioma using gene expression arrays. In the current study, they analyzed the expression of low-molecular weight (LMW) forms of cyclin E in ovarian carcinoma, malignant mesothelioma, and benign reactive effusions.


METHODS
Cyclin E protein expression was analyzed in 98 effusions (72 ovarian carcinomas, 14 malignant mesotheliomas, and 12 reactive specimens) using immunoblotting. Sixty-two ovarian carcinoma effusions were studied further for cyclin E expression using immunohistochemistry. The correlations between cyclin E expression in ovarian carcinoma and clinical parameters, including chemotherapy response, were analyzed.


RESULTS
LMW forms of cyclin E were identified in 54 of 72 ovarian carcinoma effusions (75%) compared with 1 of 14 malignant mesothelioma effusions (7%) and 1 of 12 reactive effusions (8%) (P < .001). Their presence in ovarian carcinoma was associated with a higher percentage of cyclin E-positive cells (P = .001) and increased staining intensity (P < .001) using immunohistochemistry. The presence of LMW forms of cyclin E was correlated with shorter overall survival (P = .021) and progression-free survival (P = .020). The presence of a higher percentage of cyclin E-positive cells using immunohistochemistry was correlated with shorter progression-free survival (P = .026). No association with chemotherapy response was observed.


CONCLUSIONS
LMW forms of cyclin E differentiated ovarian carcinoma from benign and malignant mesothelial cells and were associated with increased protein expression using immunohistochemistry. The expression of LMW cyclin E forms was not associated with chemotherapy response, although it may be a marker of aggressive disease in patients with metastatic ovarian carcinoma.
Davidson
Ben
B
Pathology Clinic, Radiumhospitalet-Rikshospitalet Medical Center, Oslo, Norway. bend@ulrik.uio.no
Skrede
Martina
M
Silins
Ilvars
I
Shih
Ie-Ming
IeM
Trope
Claes G
CG
Flørenes
Vivi Ann
VA
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D014408:Biomarkers, Tumor / Q000032:analysis*; D002277:Carcinoma / Q000737:chemistry* / Q000401:mortality*; D019927:Cyclin E / Q000032:analysis*; D018572:Disease-Free Survival; D005260:Female; D006801:Humans; D015151:Immunoblotting; D007150:Immunohistochemistry; D008654:Mesothelioma / Q000737:chemistry* / Q000401:mortality*; D008875:Middle Aged; D008970:Molecular Weight; D010051:Ovarian Neoplasms / Q000737:chemistry* / Q000401:mortality*; D016019:Survival Analysis
D014408:Biomarkers, Tumor; D019927:Cyclin E