Estrogen receptor 1 mRNA is a prognostic factor in ovarian carcinoma: determination by kinetic PCR in formalin-fixed paraffin-embedded tissue.
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 anti-estrogenic 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 ERalpha 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 (HR) 0.230 (confidence interval (CI) 0.102-0.516), P=0.002). ERalpha protein expression was correlated to ESR1 mRNA expression (P=0.0001); however, ERalpha 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 ERalpha protein expression (HR 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 FFPE tissue.
Darb-Esfahani
Silvia
S
Institute of Pathology, Charité Universitätsmedizin Berlin, Berlin, Germany. silvia.darb-esfahani@charite.de
Wirtz
Ralph M
RM
Sinn
Bruno V
BV
Budczies
Jan
J
Noske
Aurelia
A
Weichert
Wilko
W
Faggad
Areeg
A
Scharff
Susanne
S
Sehouli
Jalid
J
Oskay-Ozcelik
Guelten
G
Zamagni
Claudio
C
De Iaco
Pierandrea
P
Martoni
Andrea
A
Dietel
Manfred
M
Denkert
Carsten
C
D018262:Adenocarcinoma, Clear Cell / Q000235:genetics / Q000378:metabolism / Q000556:secondary; D002288:Adenocarcinoma, Mucinous / Q000235:genetics / Q000378:metabolism / Q000556:secondary; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D014408:Biomarkers, Tumor / Q000235:genetics / Q000378:metabolism; D002295:Carcinoma, Transitional Cell / Q000235:genetics / Q000378:metabolism / Q000556:secondary; D018284:Cystadenocarcinoma, Serous / Q000235:genetics / Q000378:metabolism / Q000556:secondary; D016889:Endometrial Neoplasms / Q000235:genetics / Q000378:metabolism / Q000556:secondary; D047628:Estrogen Receptor alpha / Q000235:genetics* / Q000378:metabolism; D005260:Female; D006801:Humans; D007124:Immunoenzyme Techniques; D008875:Middle Aged; D010051:Ovarian Neoplasms / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D016612:Paraffin Embedding; D011379:Prognosis; D012333:RNA, Messenger / Q000235:genetics* / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction
D014408:Biomarkers, Tumor; C506487:ESR1 protein, human; D047628:Estrogen Receptor alpha; D012333:RNA, Messenger