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S Darb-Esfahani, Institute of Pathology, Charite Universitaetsmedizin Berlin, Berlin, Germany
R Wirtz, Siemens Healthcare Diagnostics, Cologne, Germany
B Sinn, Institute of Pathology, Charite Universitaetsmedizin Berlin, Berlin, Germany
J Budczies, Institute of Pathology, Charite Universitaetsmedizin Berlin, Berlin, Germany
A Noske, Institute of Pathology, Charite Universitaetsmedizin Berlin, Berlin, Germany
W Weichert, Institute of Pathology, Charite Universitaetsmedizin Berlin, Berlin, Germany
A Faggad, Institute of Pathology, Charite Universitaetsmedizin Berlin, Berlin, Germany
S Scharff, Siemens Healthcare Diagnostics, Cologne, Germany
J Sehouli, Department of Gynaecology and Obstetrics, Charite Universitaetsmedizin Berlin, Berlin, Germany
G Oskay-Oezcelik, Department of Gynaecology and Obstetrics, Charite Universitaetsmedizin Berlin, Berlin, Germany
C Zamagni, Medical Oncology Unit, S.-Orsola-Malpighi Hospital, Bologna, Italy
P De Iaco, Obstetrics and Gynaecology Unit, S.-Orsola-Malpighi Hospital, Bologna, Italy
A Martoni, Medical Oncology Unit, S.-Orsola-Malpighi Hospital, Bologna, Italy
M Dietel, Berlin , Germany
C Denkert, Institute of Pathology, Charite Universitaetsmedizin Berlin, Berlin, Germany

Correspondence: Silvia Darb-Esfahani, Email: silvia.darb-esfahani{at}charite.de

Abstract

Epidemiological and cell culture studies indicate that ovarian carcinoma growth is dependent on estrogen stimulation. However, possibly due to the lack of a reliable biomarker that helps to select patients according to prognostically relevant estrogen receptor (ER) levels, clinical trials using antiestrogenic therapeutics in ovarian carcinoma have had inconsistent results. Therefore, we tested if ER expression analysis by a quantitative method might be useful in this regard in formalin-fixed paraffin-embedded (FFPE) tissue. In a study group of 114 primary ovarian carcinomas expression of estrogen receptor 1 (ESR1) mRNA was analyzed using a new method for RNA extraction from FFPE tissue that is based on magnetic beads, followed by kinetic PCR. The prognostic impact of ESR1 mRNA expression was investigated and compared to ER protein expression as determined by immunohistochemistry. In univariate survival analysis the expression level of ESR1 mRNA was a significant positive prognostic factor for patient survival (hazard ratio 0.230 (CI 0.102-0.516), p=0.002). ER protein expression was correlated to ESR1 mRNA expression (p=0.0001); however, ER protein expression did not provide statistically significant prognostic information. In multivariate analysis ESR1 mRNA expression emerged as a prognostic factor, independent of stage, grade, residual tumor mass, age, and ER protein expression (hazard ratio 0.227 (CI 0.078-0.656), p=0.006). Our results indicate that the determination of ESR1 levels by kinetic PCR may be superior to immunohistochemical methods in assessment of biologically relevant levels of ER expression in ovarian carcinoma, and is feasible in routinely used formalin-fixed paraffin-embedded tissue.