Quantitative In Situ Measurement of Estrogen Receptor mRNA Predicts Response to Tamoxifen 英文参考文献.docVIP

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Quantitative In Situ Measurement of Estrogen Receptor mRNA Predicts Response to Tamoxifen 英文参考文献.doc

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Quantitative In Situ Measurement of Estrogen Receptor mRNA Predicts Response to Tamoxifen 英文参考文献

QuantitativeInSituMeasurementofEstrogenReceptor mRNAPredictsResponsetoTamoxifen JenniferM.Bordeaux1,HuanCheng1,AllisonW.Welsh1,BruceG.Haffty1,DonaldR.Lannin1, XingyongWu2,NanSu2,Xiao-JunMa2,YulingLuo2,DavidL.Rimm1* 1Department ofPathology, Yale UniversitySchool ofMedicine,NewHaven,Connecticut,UnitedStates ofAmerica,2Advanced CellDiagnostics,Hayward,California, UnitedStatesofAmerica Abstract Purpose:QuantificationofmRNAhashistoricallybeendonebyreversetranscriptionpolymerasechainreaction(RT-PCR). Recently,arobustmethodofdetectionofmRNAutilizinginsituhybridizationhasbeendescribedthatislinearandshows highspecificitywithlowbackground.HerewedescribetheuseoftheAQUAmethodofquantitativeimmunofluorescence (QIF)formeasuringmRNAinsituusingESR1(theestrogenreceptoralphagene)inbreastcancertodetermineitspredictive valuecomparedtoEstrogenReceptora(ER)protein. Methods: Messenger RNA for ER (ESR1) and Ubiquitin C (UbC) were visualized using RNAscope probes and levels were quantifiedbyquantitativeinsituhybridization(qISH)ontwoYalebreastcancercohortsontissuemicroarrays.ESR1levels werecomparedtoERproteinlevelsmeasuredbyQIFusingtheSP1antibody. Results:ESR1mRNAisreproduciblyandspecificallymeasurablebyqISHontissuecollectedfrom1993orlater.ESR1levels were correlated to ER protein levels in a non-linear manner on two Yale cohorts. High levels of ESR1 were found to be predictiveofresponsetotamoxifin. Conclusion:QuantificationofmRNAusingqISHmayallowassessmentoflargecohortswithminimalformalinfixed,paraffin embeddedtissue.ExploratorydatausingthismethodsuggeststhatmeasurementofESR1mRNAlevelsmaybepredictiveof responsetoendocrinetherapyinamannerthatisdifferentfromthepredictivevalueofER. Citation:BordeauxJM,ChengH,WelshAW,HafftyBG,LanninDR,etal.(2012)QuantitativeInSituMeasurementofEstrogenReceptormRNAPredictsResponse toTamoxifen.PLoSONE7(5):e36559.doi:10.1371/journal.pone.0036559 Editor:GayleE.Woloschak,NorthwesternUniversityFeinbergSchoolofMedicine,UnitedStatesofAmerica ReceivedJanuary23,2012;A