2021
Alpha-smooth muscle actin expression in the stroma predicts resistance to trastuzumab in patients with early-stage HER2-positive breast cancer
Vathiotis IA, Moutafi MK, Divakar P, Aung TN, Qing T, Fernandez A, Yaghoobi V, El-Abed S, Wang Y, Guillaume S, Nuciforo P, Huober J, Di Cosimo S, Kim SB, Harbeck N, Gomez H, Shafi S, Syrigos KN, Fountzilas G, Sotiriou C, Pusztai L, Warren S, Rimm DL. Alpha-smooth muscle actin expression in the stroma predicts resistance to trastuzumab in patients with early-stage HER2-positive breast cancer. Clinical Cancer Research 2021, 27: 6156-6163. PMID: 34465600, PMCID: PMC8595766, DOI: 10.1158/1078-0432.ccr-21-2103.Peer-Reviewed Original ResearchConceptsDisease-free survivalHER2-positive breast cancerShorter disease-free survivalBreast cancerQuantitative immunofluorescenceEarly-stage HER2-positive breast cancerAlpha-smooth muscle actin expressionAlpha-smooth muscle actinProgesterone receptor statusHigh α-SMA expressionDigital Spatial ProfilerΑ-SMA expressionPromising candidate biomarkerCompanion diagnostic testsMuscle actin expressionDigital spatial profilingCohort validationNeoadjuvant lapatinibAdjuvant trastuzumabReceptor statusClinical trialsUnivariate analysisEstrogen receptorMAIN OUTCOMEΑ-SMA
2020
Assessment of Ki67 in Breast Cancer: Updated Recommendations From the International Ki67 in Breast Cancer Working Group
Nielsen TO, Leung SCY, Rimm DL, Dodson A, Acs B, Badve S, Denkert C, Ellis MJ, Fineberg S, Flowers M, Kreipe HH, Laenkholm AV, Pan H, Penault-Llorca FM, Polley MY, Salgado R, Smith IE, Sugie T, Bartlett JMS, McShane LM, Dowsett M, Hayes DF. Assessment of Ki67 in Breast Cancer: Updated Recommendations From the International Ki67 in Breast Cancer Working Group. Journal Of The National Cancer Institute 2020, 113: 808-819. PMID: 33369635, PMCID: PMC8487652, DOI: 10.1093/jnci/djaa201.Peer-Reviewed Original ResearchConceptsBreast cancerClinical utilityKi67 immunohistochemistryInternational Ki67Breast Cancer Working GroupAnalytical validityAssessment of Ki67HER2-negative patientsBreast cancer careCancer Working GroupGroup consensus meetingAdjuvant chemotherapyVisual scoring methodPatient groupCancer careT1-2Prognostic markerPrognosis assessmentPrognosis estimationTreatment decisionsEstrogen receptorHER2 testingConsensus meetingCurrent evidenceClinical validityEstrogen and Progesterone Receptor Testing in Breast Cancer: American Society of Clinical Oncology/College of American Pathologists Guideline Update
Allison KH, Hammond MEH, Dowsett M, McKernin SE, Carey LA, Fitzgibbons PL, Hayes DF, Lakhani SR, Chavez-MacGregor M, Perlmutter J, Perou CM, Regan MM, Rimm DL, Symmans WF, Torlakovic EE, Varella L, Viale G, Weisberg TF, McShane LM, Wolff AC. Estrogen and Progesterone Receptor Testing in Breast Cancer: American Society of Clinical Oncology/College of American Pathologists Guideline Update. Archives Of Pathology & Laboratory Medicine 2020, 144: 545-563. PMID: 31928354, DOI: 10.5858/arpa.2019-0904-sa.Peer-Reviewed Original ResearchConceptsClinical Oncology/CollegeProgesterone receptor testingEstrogen receptorBreast cancerEndocrine therapyReceptor testingExpert panelAmerican Pathologists (CAP) guideline updatesClinical practice guideline recommendationsMultidisciplinary international expert panelEndocrine therapy benefitPractice guideline recommendationsBreast cancer guidelinesER-positive cancersInvasive breast cancerFuture breast cancerAmerican SocietyBreast cancer samplesInternational expert panelReporting of casesPgR testingTumor cell nucleiCancer guidelinesGuideline recommendationsGuideline update
2018
Correlating nuclear morphometric patterns with estrogen receptor status in breast cancer pathologic specimens
Rawat RR, Ruderman D, Macklin P, Rimm DL, Agus DB. Correlating nuclear morphometric patterns with estrogen receptor status in breast cancer pathologic specimens. Npj Breast Cancer 2018, 4: 32. PMID: 30211313, PMCID: PMC6123433, DOI: 10.1038/s41523-018-0084-4.Peer-Reviewed Original ResearchEstrogen receptor statusInvasive ductal carcinomaER statusEstrogen receptorReceptor statusPercent of cellsHormonal therapyDuctal carcinomaImmunohistochemistry stainingHistology patternPathway statusPatient samplesPathway activationPilot studyNuclear featuresDeep neural networksTissue coresNeural networkReceptorsFuture studiesStatusTissue morphologyBiological featuresDeep learning approachCarcinomaMacrodissection prior to closed system RT-qPCR is not necessary for estrogen receptor and HER2 concordance with IHC/FISH in breast cancer
Gupta S, Mani NR, Carvajal-Hausdorf DE, Bossuyt V, Ho K, Weidler J, Wong W, Rhees B, Bates M, Rimm DL. Macrodissection prior to closed system RT-qPCR is not necessary for estrogen receptor and HER2 concordance with IHC/FISH in breast cancer. Laboratory Investigation 2018, 98: 1076-1083. PMID: 29858579, PMCID: PMC6119113, DOI: 10.1038/s41374-018-0064-1.Peer-Reviewed Original ResearchMeSH KeywordsBiomarkers, TumorBreast NeoplasmsCarcinoma, Ductal, BreastCarcinoma, Intraductal, NoninfiltratingFemaleGene Expression Regulation, NeoplasticHumansImmunohistochemistryIn Situ Hybridization, FluorescenceParaffin EmbeddingPathology, ClinicalReal-Time Polymerase Chain ReactionReceptor, ErbB-2Receptors, EstrogenReproducibility of ResultsSensitivity and SpecificityTissue FixationConceptsIHC/FISHDCIS cohortRT-qPCRMRNA transcript levelsDuctal carcinoma casesFine needle aspiratesMRNA expression levelsHER2 concordanceER positivityDuctal carcinomaHER2 expressionGeneXpert systemCarcinoma casesInvasive tumorsNeedle biopsyBreast cancerEstrogen receptorClinical ImmunohistochemistryBiopsy areaTumor tissueMRNA expressionTumor areaCohortMRNA levelsMRNA markersTumor infiltrating lymphocytes and PD-L1 expression in pre- and post-treatment breast cancers in the SWOG S0800 Phase II neoadjuvant chemotherapy trial
Pelekanou V, Barlow WE, Nahleh Z, Wasserman B, Lo YC, von Wahlde MK, Hayes D, Hortobagyi GN, Gralow J, Tripathy D, Porter P, Szekely B, Hatzis C, Rimm DL, Pusztai L. Tumor infiltrating lymphocytes and PD-L1 expression in pre- and post-treatment breast cancers in the SWOG S0800 Phase II neoadjuvant chemotherapy trial. Molecular Cancer Therapeutics 2018, 17: molcanther.1005.2017. PMID: 29588392, PMCID: PMC6548451, DOI: 10.1158/1535-7163.mct-17-1005.Peer-Reviewed Original ResearchConceptsPD-L1 expressionPathologic complete responseTIL countPosttreatment tissuePD-L1Estrogen receptorImmune checkpoint inhibitor therapyPD-L1 positivity rateTumor-infiltrating lymphocyte countsDoxorubicin/cyclophosphamideCheckpoint inhibitor therapyPD-L1 levelsMol Cancer TherNab-paclitaxelLymphocyte countResidual cancerComplete responseER statusImmune changesInhibitor therapyCox regressionPatient populationControl armClinical trialsPositivity rate
2017
Calcium Sensor, NCS-1, Promotes Tumor Aggressiveness and Predicts Patient Survival
Moore LM, England A, Ehrlich BE, Rimm DL. Calcium Sensor, NCS-1, Promotes Tumor Aggressiveness and Predicts Patient Survival. Molecular Cancer Research 2017, 15: 942-952. PMID: 28275088, PMCID: PMC5500411, DOI: 10.1158/1541-7786.mcr-16-0408.Peer-Reviewed Original ResearchConceptsBreast cancer cellsNCS-1Breast cancer patient cohortsNCS-1 expressionLymph node statusCancer cellsShorter survival rateIndependent breast cancer cohortsCancer patient cohortsBreast cancer cohortMB-231 breast cancer cellsPaclitaxel-induced cell deathAggressive tumor phenotypeNeuronal model systemClinical outcomesClinicopathologic featuresNeuronal calcium sensor-1Node statusPatient cohortProgesterone receptorWorse outcomesBreast cancerCalcium-binding proteinsCancer cohortEstrogen receptor
2015
Loss of antigenicity with tissue age in breast cancer
Combs SE, Han G, Mani N, Beruti S, Nerenberg M, Rimm DL. Loss of antigenicity with tissue age in breast cancer. Laboratory Investigation 2015, 96: 264-269. PMID: 26568292, DOI: 10.1038/labinvest.2015.138.Peer-Reviewed Original ResearchConceptsHuman epidermal growth receptor 2Estrogen receptorQuantitative immunofluorescenceProtein expressionSeries of formalinRandom-effects modelHuman breast carcinomaLarge cooperative groupsParaffin-embedded tissuesKi67 expressionBreast carcinomaBreast cancerIndividual patientsTissue microarrayClinical investigationClinical questionsReceptor 2Tumor specimensPositive casesLoss of antigenicityFFPE biospecimensQuantitative protein expressionBiomarkersCooperative groupsPreservation time
2014
ERβ splice variant expression in four large cohorts of human breast cancer patient tumors
Wimberly H, Han G, Pinnaduwage D, Murphy LC, Yang XR, Andrulis IL, Sherman M, Figueroa J, Rimm DL. ERβ splice variant expression in four large cohorts of human breast cancer patient tumors. Breast Cancer Research And Treatment 2014, 146: 657-667. PMID: 25007965, PMCID: PMC6939385, DOI: 10.1007/s10549-014-3050-3.Peer-Reviewed Original ResearchConceptsBreast cancerPatient tumorsERβ variantsQuantitative immunofluorescenceBreast cancer patient tumorsTriple-negative patientsBreast cancer outcomesAbsence of ERαBreast cancer biologyCancer patient tumorsBreast cancer patient samplesSplice variant expressionCancer patient samplesParaffin-embedded tissuesQIF scoresCancer outcomesPredictive biomarkersWorse outcomesEstrogen receptorLarge cohortSurvival analysisERβPatient samplesAQUA technologyVariant expression
2013
In situ techniques for protein analysis in tumor tissue
Anagnostou V, Rimm D. In situ techniques for protein analysis in tumor tissue. 2013, 76-84. DOI: 10.1017/cbo9781139046947.010.Peer-Reviewed Original ResearchSignal amplification techniqueProtein detectionAntigen of interestConventional IHCAntigen-antibody reactionLow costHuman epidermal growth factor receptor 2Epidermal growth factor receptor 2Growth factor receptor 2Selection of patientsComplementary diagnostic informationSitu techniquesFactor receptor 2Companion diagnostic testsCurrent analytical techniquesParaffin-embedded tissuesHistological diagnosisSpecific therapyDefinite diagnosisHistological subclassificationBreast cancerPrognostic biomarkerEstrogen receptorReceptor 2Morphologic evaluation
2012
Quantitative Assessment of Effect of Preanalytic Cold Ischemic Time on Protein Expression in Breast Cancer Tissues
Neumeister VM, Anagnostou V, Siddiqui S, England AM, Zarrella ER, Vassilakopoulou M, Parisi F, Kluger Y, Hicks DG, Rimm DL. Quantitative Assessment of Effect of Preanalytic Cold Ischemic Time on Protein Expression in Breast Cancer Tissues. Journal Of The National Cancer Institute 2012, 104: 1815-1824. PMID: 23090068, PMCID: PMC3514166, DOI: 10.1093/jnci/djs438.Peer-Reviewed Original ResearchMeSH KeywordsA Kinase Anchor ProteinsBiomarkers, TumorBiopsy, Large-Core NeedleBreast NeoplasmsCold IschemiaConfounding Factors, EpidemiologicFalse Negative ReactionsFemaleFixativesFluorescent Antibody TechniqueFormaldehydeGene Expression Regulation, NeoplasticHumansHypoxia-Inducible Factor 1, alpha SubunitKi-67 AntigenMastectomy, SegmentalMatched-Pair AnalysisMinor Histocompatibility AntigensProspective StudiesProto-Oncogene ProteinsReceptor, ErbB-2Receptors, EstrogenReceptors, ProgesteroneResearch DesignTime FactorsConceptsCold ischemic timeIschemic timeBreast cancer tissuesEstrogen receptorCancer tissuesLoss of antigenicityBreast cancer resectionProtein expressionCore needle biopsyCompanion diagnostic testsConditions of hypoxiaFalse-negative resultsBreast cancer biomarkersCancer resectionProgesterone receptorNeedle biopsyRecent guidelinesCold ischemiaBreast cancerTissue microarrayEvidence of lossQuantitative immunofluorescenceDiagnostic testsAntigenicityAQUA methodCytoplasmic Estrogen Receptor in Breast Cancer
Welsh AW, Lannin DR, Young GS, Sherman ME, Figueroa JD, Henry NL, Ryden L, Kim C, Love RR, Schiff R, Rimm DL. Cytoplasmic Estrogen Receptor in Breast Cancer. Clinical Cancer Research 2012, 18: 118-126. PMID: 21980134, PMCID: PMC3263348, DOI: 10.1158/1078-0432.ccr-11-1236.Peer-Reviewed Original ResearchConceptsEstrogen receptorCytoplasmic stainingCytoplasmic ERCytoplasmic estrogen receptorSpecific cytoplasmic stainingCell line seriesHuman breast tumorsQuantitative immunofluorescent analysisRoutine clinical valueRetrospective cohortTamoxifen resistanceBreast cancerLower incidencePreclinical modelsClinical valueTissue microarrayPatient controlsBreast tumorsNumber of casesClinical specimensMultiple antibodiesWestern blotAverage incidenceAntibodiesCohort
2011
Targeting Androgen Receptor in Estrogen Receptor-Negative Breast Cancer
Ni M, Chen Y, Lim E, Wimberly H, Bailey ST, Imai Y, Rimm DL, Liu XS, Brown M. Targeting Androgen Receptor in Estrogen Receptor-Negative Breast Cancer. Cancer Cell 2011, 20: 119-131. PMID: 21741601, PMCID: PMC3180861, DOI: 10.1016/j.ccr.2011.05.026.Peer-Reviewed Original ResearchMeSH KeywordsAndrogensAnilidesAnimalsBeta CateninBreast NeoplasmsCell Line, TumorCell ProliferationDihydrotestosteroneFemaleGene Expression ProfilingGene Expression Regulation, NeoplasticHepatocyte Nuclear Factor 3-alphaHumansMiceNitrilesReceptor, ErbB-2Receptors, AndrogenReceptors, EstrogenSignal TransductionTosyl CompoundsTranscriptional ActivationUp-RegulationWnt ProteinsXenograft Model Antitumor AssaysConceptsAndrogen receptorBreast cancerEstrogen receptorER-/HER2Estrogen receptor-negative breast cancerReceptor-negative breast cancerBreast cancer growthER- breast tumorsPotential therapeutic approachTumor cell growthAndrogen-regulated gene expressionEndocrine therapyER statusTherapeutic approachesAR cistromeBreast tumorsCancer growthDirect transcriptional inductionCancerHER2Ligand-dependent activationReceptorsSpecific targetingTumorsCell growthStandardization of Estrogen Receptor Measurement in Breast Cancer Suggests False-Negative Results Are a Function of Threshold Intensity Rather Than Percentage of Positive Cells
Welsh AW, Moeder CB, Kumar S, Gershkovich P, Alarid ET, Harigopal M, Haffty BG, Rimm DL. Standardization of Estrogen Receptor Measurement in Breast Cancer Suggests False-Negative Results Are a Function of Threshold Intensity Rather Than Percentage of Positive Cells. Journal Of Clinical Oncology 2011, 29: 2978-2984. PMID: 21709197, PMCID: PMC3157961, DOI: 10.1200/jco.2010.32.9706.Peer-Reviewed Original ResearchConceptsER-positive patientsEstrogen receptorQuantitative immunofluorescenceBreast cancerTissue microarrayPositive cellsIndependent retrospective cohortsEstrogen receptor measurementsAssessment of survivalTMA cohortFalse-negative resultsRetrospective cohortER immunoreactivityTest discordancePrognostic outcomesIndependent cohortReceptor measurementsLimitations of immunohistochemistryPatientsDiscrepant casesCohortIHC methodPathologists' judgmentsDiscrepant resultsStandardized assaysOptimal tumor sampling for immunostaining of biomarkers in breast carcinoma
Tolles J, Bai Y, Baquero M, Harris LN, Rimm DL, Molinaro AM. Optimal tumor sampling for immunostaining of biomarkers in breast carcinoma. Breast Cancer Research 2011, 13: r51. PMID: 21592345, PMCID: PMC3218938, DOI: 10.1186/bcr2882.Peer-Reviewed Original ResearchConceptsWhole tissue sectionsBreast carcinomaEstrogen receptorBiomarker expressionTumor biomarker expressionAmount of tumorTissue sectionsEvidence-based standardsHeterogeneous markersTherapeutic responseHER-2Optimal tumorBreast biopsyBreast tumorsClinical implicationsMAP-tauQuantitative immunofluorescenceClinical useLevel of expressionCarcinomaImmunostaining assaysBiomarkersTumorsTissue samplesBiomarker heterogeneityQuantitative assessment shows loss of antigenic epitopes as a function of pre-analytic variables
Bai Y, Tolles J, Cheng H, Siddiqui S, Gopinath A, Pectasides E, Camp RL, Rimm DL, Molinaro AM. Quantitative assessment shows loss of antigenic epitopes as a function of pre-analytic variables. Laboratory Investigation 2011, 91: 1253-1261. PMID: 21519325, PMCID: PMC3145004, DOI: 10.1038/labinvest.2011.75.Peer-Reviewed Original ResearchConceptsCore needle biopsyCold ischemic timePre-analytic variablesNeedle biopsyEstrogen receptorIschemic timeTumor resectionTumor resection specimensAntigenic lossResection specimensTissue biomarkersTotal AktBiopsyPhospho-AktQuantitative immunofluorescencePhospho-ERKPhospho-S6K1Antigenic epitopesTotal ERKResectionTotal proteinCytokeratinImmunological methodsAntigenicitySignificant changes
2010
Pre-analytic variables and phospho-specific antibodies: the Achilles heel of immunohistochemistry
Siddiqui S, Rimm DL. Pre-analytic variables and phospho-specific antibodies: the Achilles heel of immunohistochemistry. Breast Cancer Research 2010, 12: 113. PMID: 21176180, PMCID: PMC3046444, DOI: 10.1186/bcr2782.Peer-Reviewed Original ResearchConceptsCold ischemic timePre-analytic variablesIschemic timeCore needle biopsyCompanion diagnostic testingCompanion diagnostic testsBreast cancer researchProgesterone receptorNeedle biopsyBreast cancerEstrogen receptorCritical therapyDiagnostic testingDiagnostic testsClassic markersImmunohistochemistryCancer researchPhospho-specific antibodiesReceptorsMarkersAchilles heelAnalytic Variability in Immunohistochemistry Biomarker Studies
Anagnostou VK, Welsh AW, Giltnane JM, Siddiqui S, Liceaga C, Gustavson M, Syrigos KN, Reiter JL, Rimm DL. Analytic Variability in Immunohistochemistry Biomarker Studies. Cancer Epidemiology Biomarkers & Prevention 2010, 19: 982-991. PMID: 20332259, PMCID: PMC3891912, DOI: 10.1158/1055-9965.epi-10-0097.Peer-Reviewed Original ResearchConceptsHuman epidermal growth factor receptor 3Cancer patientsEstrogen receptorWestern blottingBiomarker studiesEpidermal growth factor receptor 1Breast cancer patientsLung cancer patientsEpidermal growth factor receptor 3Growth factor receptor 1Factor receptor 1Growth factor receptor 3Clone 1D5Worse prognosisHigher eGFRPrognostic classificationER antibodyCancer-related biomarkersCutoff pointBT474 cellsSurvival analysisEGFR antibodyReceptor 1Receptor 3Quantitative immunofluorescenceMultiplexed Assessment of the Southwest Oncology Group-Directed Intergroup Breast Cancer Trial S9313 by AQUA Shows that Both High and Low Levels of HER2 Are Associated with Poor Outcome
Harigopal M, Barlow WE, Tedeschi G, Porter PL, Yeh IT, Haskell C, Livingston R, Hortobagyi GN, Sledge G, Shapiro C, Ingle JN, Rimm DL, Hayes DF. Multiplexed Assessment of the Southwest Oncology Group-Directed Intergroup Breast Cancer Trial S9313 by AQUA Shows that Both High and Low Levels of HER2 Are Associated with Poor Outcome. American Journal Of Pathology 2010, 176: 1639-1647. PMID: 20150438, PMCID: PMC2843456, DOI: 10.2353/ajpath.2010.090711.Peer-Reviewed Original ResearchConceptsDisease-free survivalEstrogen receptorContinuous variablesSouthwest Oncology GroupAQUA methodAC chemotherapyMenopausal statusNegative patientsOncology GroupNode statusSequential doxorubicinPoor outcomeTumor sizeProgesterone receptorPrognostic informationWorse outcomesTissue biomarkersTissue microarrayBiphasic effectP53 expressionPatientsHER2Low expressersDiagnostic approachMultiplexed assessment
2009
Evaluation of the false-negative rate of standardized and quantitative measurement of estrogen receptor (ER) in tissue using AQUA technology
Gustavson M, Welsh A, Jones C, Mayotte J, Tu J, Hopkins J, Rimm D, Christiansen J. Evaluation of the false-negative rate of standardized and quantitative measurement of estrogen receptor (ER) in tissue using AQUA technology. Journal Of Clinical Oncology 2009, 27: 567-567. DOI: 10.1200/jco.2009.27.15_suppl.567.Peer-Reviewed Original ResearchER protein expressionEstrogen receptorBreast cancer samplesPg/AQUA analysisFalse negative rateAQUA technologyCancer samplesAllred scoring systemProtein expressionChange of diagnosisEstrogen receptor testingReproducible diagnostic testFalse-negative testsHigh false-negative rateReceptor testingER testingAllred scoreLarge cohortNegative testAQUA scoreScoring systemMisclassified casesClinical settingConcordance rate