原创力文档quantitative in situ measurement of estrogen receptor mrna predicts response to tamoxifen雌激素受体信使rna原位定量测量预测应对它莫西芬.pdfVIP
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quantitative in situ measurement of estrogen receptor mrna predicts response to tamoxifen雌激素受体信使rna原位定量测量预测应对它莫西芬
Quantitative In Situ Measurement of Estrogen Receptor
mRNA Predicts Response to Tamoxifen
1 1 1 1 1
Jennifer M. Bordeaux , Huan Cheng , Allison W. Welsh , Bruce G. Haffty , Donald R. Lannin ,
2 2 2 2 1
Xingyong Wu , Nan Su , Xiao-Jun Ma , Yuling Luo , David L. Rimm *
1 Department of Pathology, Yale University School of Medicine, New Haven, Connecticut, United States of America, 2 Advanced Cell Diagnostics, Hayward, California,
United States of America
Abstract
Purpose: Quantification of mRNA has historically been done by reverse transcription polymerase chain reaction (RT-PCR).
Recently, a robust method of detection of mRNA utilizing in situ hybridization has been described that is linear and shows
high specificity with low background. Here we describe the use of the AQUA method of quantitative immunofluorescence
(QIF) for measuring mRNA in situ using ESR1 (the estrogen receptor alpha gene) in breast cancer to determine its predictive
value compared to Estrogen Receptor a (ER) protein.
Methods: Messenger RNA for ER (ESR1) and Ubiquitin C (UbC) were visualized using RNAscope probes and levels were
quantified by quantitative in situ hybridization (qISH) on two Yale breast cancer cohorts on tissue microarrays. ESR1 levels
were compared to ER protein levels measured by QIF using the SP1 antibody.
Results: ESR1 mRNA is reproducibly and specifically measurable by qISH on tissue collected from 1993 or later. ESR1 levels
were correlated to ER protein levels in a non-linear manner on two Yale cohorts. High levels of ESR1 were found to be
predictive of response to tamoxifin.
Conclusion: Quantification of mRNA using
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