Low-molecular weight forms of cyclin E differentiate ovarian carcinoma from cells of mesothelial origin and are associated with poor survival in ovarian carcinoma

Authors

  • Ben Davidson MD, PhD,

    Corresponding author
    1. Pathology Clinic, Radiumhospitalet-Rikshospitalet Medical Center, Oslo, Norway
    2. Faculty Division Radiumhospitalet, the Medical Faculty, University of Oslo, Oslo, Norway
    • Department of Pathology, Radiumhospitalet-Rikshospitalet Medical Center, Montebello N-0310 Oslo, Norway
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    • Fax: (011) 47 22508554

  • Martina Skrede,

    1. Pathology Clinic, Radiumhospitalet-Rikshospitalet Medical Center, Oslo, Norway
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  • Ilvars Silins MD, PhD,

    1. Department of Gynecology, Radiumhospitalet-Rikshospitalet Medical Center, Oslo, Norway
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  • Ie-Ming Shih MD, PhD,

    1. Department of Pathology, Johns Hopkins Medical Institutions, Baltimore, Maryland
    2. Department of Gynecology and Oncology, Johns Hopkins Medical Institutions, Baltimore, Maryland
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  • Claes G. Trope MD, PhD,

    1. Faculty Division Radiumhospitalet, the Medical Faculty, University of Oslo, Oslo, Norway
    2. Department of Gynecology, Radiumhospitalet-Rikshospitalet Medical Center, Oslo, Norway
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  • Vivi Ann Flørenes PhD

    1. Pathology Clinic, Radiumhospitalet-Rikshospitalet Medical Center, Oslo, Norway
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Abstract

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. Cancer 2007. © 2007 American Cancer Society.

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