2024
An algorithm for standardization of tumor Infiltrating lymphocyte evaluation in head and neck cancers
Xirou V, Moutafi M, Bai Y, Nwe Aung T, Burela S, Liu M, Kimple R, Shabbir Ahmed F, Schultz B, Flieder D, Connolly D, Psyrri A, Burtness B, Rimm D. An algorithm for standardization of tumor Infiltrating lymphocyte evaluation in head and neck cancers. Oral Oncology 2024, 152: 106750. PMID: 38547779, PMCID: PMC11060915, DOI: 10.1016/j.oraloncology.2024.106750.Peer-Reviewed Original ResearchConceptsTumor-infiltrating lymphocytesHead and neck cancerTILs evaluationHPV-positiveNeck cancerPrognostic valueHead and neck squamous cell cancer casesTIL variablesAssociated with favorable prognosisHPV-negative headHPV-negative populationHematoxylin-eosin-stained sectionsCox regression analysisPotential clinical implicationsInter-observer variabilityInfiltrating lymphocytesClinicopathological factorsFavorable prognosisValidation cohortTumor cellsCancer casesProspective settingQuPath softwareRetrospective collectionPredictive significance
2022
Quantitative measurement of HER2 expression to subclassify ERBB2 unamplified breast cancer.
Moutafi M, Robbins C, Yaghoobi V, Fernandez A, Martinez-Morilla S, Xirou V, Bai Y, Song Y, Gaule P, Krueger J, Bloom K, Hill S, Liebler D, Fulton R, Rimm D. Quantitative measurement of HER2 expression to subclassify ERBB2 unamplified breast cancer. Laboratory Investigation 2022, 102: 1101-1108. PMID: 36775350, DOI: 10.1038/s41374-022-00804-9.Peer-Reviewed Original ResearchConceptsHER2 expressionBreast cancerAttomol/HER2 proteinBreast cancer patientsBreast cancer casesOptimal patient careLevels of HER2Trastuzumab deruxtecanT-DXdCancer patientsLow HER2Cancer casesConventional assaysHER2Patient careAntibody concentrationsQuantitative immunofluorescenceAntibody drugsCancerCell linesAssaysExpressionHER2 detectionLower range
2021
An Open Source, Automated Tumor Infiltrating Lymphocyte Algorithm for Prognosis in Triple-Negative Breast Cancer
Bai Y, Cole K, Martinez-Morilla S, Ahmed FS, Zugazagoitia J, Staaf J, Bosch A, Ehinger A, Nimeus E, Hartman J, Acs B, Rimm DL. An Open Source, Automated Tumor Infiltrating Lymphocyte Algorithm for Prognosis in Triple-Negative Breast Cancer. Clinical Cancer Research 2021, 27: clincanres.0325.2021. PMID: 34088723, PMCID: PMC8530841, DOI: 10.1158/1078-0432.ccr-21-0325.Peer-Reviewed Original ResearchA new tool for technical standardization of the Ki67 immunohistochemical assay
Aung TN, Acs B, Warrell J, Bai Y, Gaule P, Martinez-Morilla S, Vathiotis I, Shafi S, Moutafi M, Gerstein M, Freiberg B, Fulton R, Rimm DL. A new tool for technical standardization of the Ki67 immunohistochemical assay. Modern Pathology 2021, 34: 1261-1270. PMID: 33536573, PMCID: PMC8222064, DOI: 10.1038/s41379-021-00745-6.Peer-Reviewed Original Research
2018
Ki67 reproducibility using digital image analysis: an inter-platform and inter-operator study
Acs B, Pelekanou V, Bai Y, Martinez-Morilla S, Toki M, Leung SCY, Nielsen TO, Rimm DL. Ki67 reproducibility using digital image analysis: an inter-platform and inter-operator study. Laboratory Investigation 2018, 99: 107-117. PMID: 30181553, DOI: 10.1038/s41374-018-0123-7.Peer-Reviewed Original ResearchAn international multicenter study to evaluate reproducibility of automated scoring for assessment of Ki67 in breast cancer
Rimm DL, Leung SCY, McShane LM, Bai Y, Bane AL, Bartlett JMS, Bayani J, Chang MC, Dean M, Denkert C, Enwere EK, Galderisi C, Gholap A, Hugh JC, Jadhav A, Kornaga EN, Laurinavicius A, Levenson R, Lima J, Miller K, Pantanowitz L, Piper T, Ruan J, Srinivasan M, Virk S, Wu Y, Yang H, Hayes DF, Nielsen TO, Dowsett M. An international multicenter study to evaluate reproducibility of automated scoring for assessment of Ki67 in breast cancer. Modern Pathology 2018, 32: 59-69. PMID: 30143750, DOI: 10.1038/s41379-018-0109-4.Peer-Reviewed Original ResearchConceptsIntraclass correlation coefficientBreast cancerBreast Cancer Working GroupAssessment of Ki67Pre-specified analysisCancer Working GroupInternational multicenter studyMulticenter studySubsequent clinical validationInternational Ki67Biopsy sectionsClinical valueBiomarker Ki67Breast tumorsKi67 immunohistochemistryEvaluation of reproducibilityKi67Clinical validationTumor cellsObserved intraclass correlation coefficientScoring methodCorrelation coefficientKi67 scoringMaximum scoreCancer
2017
Elevated T cell activation score is associated with improved survival of breast cancer
Lu L, Bai Y, Wang Z. Elevated T cell activation score is associated with improved survival of breast cancer. Breast Cancer Research And Treatment 2017, 164: 689-696. PMID: 28488141, DOI: 10.1007/s10549-017-4281-x.Peer-Reviewed Original ResearchConceptsT cell activation scoreBreast cancer patientsOverall survivalPatients' overall survivalCancer patientsImproved survivalPD-1Activation scoresBreast cancerCell death-1 receptorLow PD-1 expressionMultivariate Cox regression analysisT-lymphocyte antigen-4Kaplan-Meier survival curvesT cell activation statusDeath-1 receptorPD-1 expressionEffector T cellsImmune checkpoint blockadeCox regression analysisPoor overall survivalCox regression modelT cell functionActivation groupCell activation statusObjective, domain-specific HER2 measurement in uterine and ovarian serous carcinomas and its clinical significance
Carvajal-Hausdorf DE, Schalper KA, Bai Y, Black J, Santin AD, Rimm DL. Objective, domain-specific HER2 measurement in uterine and ovarian serous carcinomas and its clinical significance. Gynecologic Oncology 2017, 145: 154-158. PMID: 28196634, PMCID: PMC5941302, DOI: 10.1016/j.ygyno.2017.02.002.Peer-Reviewed Original ResearchMeSH KeywordsAdo-Trastuzumab EmtansineAfatinibAntibodies, Monoclonal, HumanizedAntineoplastic AgentsCohort StudiesExtracellular SpaceFemaleFluorescent Antibody TechniqueHumansIntracellular SpaceLapatinibMaytansineMiddle AgedNeoplasms, Cystic, Mucinous, and SerousOvarian NeoplasmsProtein DomainsQuinazolinesReceptor, ErbB-2Retrospective StudiesTissue Array AnalysisTrastuzumabUterine NeoplasmsConceptsUterine serous carcinomaOvarian serous carcinomaHER2 intracellular domainSerous carcinomaECD levelsECD statusTissue microarrayHER2 measurementQuantitative immunofluorescenceHER2 overexpression/amplificationClinico-pathologic characteristicsClinico-pathological featuresHER2-targeted agentsIntracellular domainOverexpression/amplificationHER2 extracellular domainExtracellular domainOSC patientsClinical trialsBreast cancerClinical significancePatientsHER2 assaysP95-HER2CarcinomaSpitz nevi and Spitzoid melanomas: exome sequencing and comparison with conventional melanocytic nevi and melanomas
Lazova R, Pornputtapong N, Halaban R, Bosenberg M, Bai Y, Chai H, Krauthammer M. Spitz nevi and Spitzoid melanomas: exome sequencing and comparison with conventional melanocytic nevi and melanomas. Modern Pathology 2017, 30: 640-649. PMID: 28186096, PMCID: PMC5413430, DOI: 10.1038/modpathol.2016.237.Peer-Reviewed Original Research
2016
Early and multiple origins of metastatic lineages within primary tumors
Zhao ZM, Zhao B, Bai Y, Iamarino A, Gaffney SG, Schlessinger J, Lifton RP, Rimm DL, Townsend JP. Early and multiple origins of metastatic lineages within primary tumors. Proceedings Of The National Academy Of Sciences Of The United States Of America 2016, 113: 2140-2145. PMID: 26858460, PMCID: PMC4776530, DOI: 10.1073/pnas.1525677113.Peer-Reviewed Original ResearchConceptsMetastatic lineagesGenetic changesEarly genetic divergenceMolecular evolutionary modelsSingle genetic changeDivergent lineagesTumor phylogeneticsDivergence timesAncestral stateGenetic divergenceCancer lineagesPhylogenetic analysisEvolutionary processesLineagesCancer evolutionMultiple originsDriver genesCancer biologyCancer progressionSomatic mutationsTumor developmentEvolutionary modelsDriver mutationsChronogramMutations
2014
Quantitative measurements of HER2 and phospho-HER2 expression: correlation with pathologic response to neoadjuvant chemotherapy and trastuzumab
Cheng H, Bai Y, Sikov W, Sinclair N, Bossuyt V, Abu-Khalaf MM, Harris LN, Rimm DL. Quantitative measurements of HER2 and phospho-HER2 expression: correlation with pathologic response to neoadjuvant chemotherapy and trastuzumab. BMC Cancer 2014, 14: 326. PMID: 24885187, PMCID: PMC4037428, DOI: 10.1186/1471-2407-14-326.Peer-Reviewed Original ResearchMeSH KeywordsAdenocarcinomaAlbuminsAntibodies, Monoclonal, HumanizedAntineoplastic Combined Chemotherapy ProtocolsBiomarkers, TumorBreast NeoplasmsCarboplatinChemotherapy, AdjuvantConnecticutFemaleFluorescent Antibody TechniqueHumansNeoadjuvant TherapyPaclitaxelPhosphorylationProteomicsReceptor, ErbB-2Rhode IslandTime FactorsTrastuzumabTreatment OutcomeConceptsLikelihood of responsePhospho-HER2Nab-paclitaxelPathologic responseHER2 levelsAdvanced HER2-positive breast cancerHER2-positive breast cancerCarboplatin combination therapyPreoperative clinical trialPre-surgical settingSingle-agent trastuzumabPathologic complete responseInitiation of treatmentWeeks of treatmentBreast cancer patientsTumor core biopsiesCore biopsy samplesMonoclonal antibody trastuzumabEvaluable patientsNeoadjuvant regimenNeoadjuvant chemotherapyNeoadjuvant therapyNeoadjuvant treatmentComplete responsePreoperative setting
2013
Comparison of HER2 and Phospho-HER2 Expression between Biopsy and Resected Breast Cancer Specimens Using a Quantitative Assessment Method
Bai Y, Cheng H, Bordeaux J, Neumeister V, Kumar S, Rimm DL, Stern DF. Comparison of HER2 and Phospho-HER2 Expression between Biopsy and Resected Breast Cancer Specimens Using a Quantitative Assessment Method. PLOS ONE 2013, 8: e79901. PMID: 24278211, PMCID: PMC3836903, DOI: 10.1371/journal.pone.0079901.Peer-Reviewed Original ResearchConceptsCore needle biopsyBreast cancer casesResection specimensCancer casesHER2/neu overexpressionPrediction of responsePre-analytic variablesNeu overexpressionTumor resectionNeedle biopsyBreast cancerHER2 immunoreactivityRetrospective collectionHER2Drug trastuzumabClinical implicationsHER2 proteinQuantitative immunofluorescenceResectionPHER2Good responseFurther studiesBiopsyTrastuzumabImmunoreactivity
2011
Optimal 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
2008
Interferon-γ Induces X-linked Inhibitor of Apoptosis-associated Factor-1 and Noxa Expression and Potentiates Human Vascular Smooth Muscle Cell Apoptosis by STAT3 Activation*
Bai Y, Ahmad U, Wang Y, Li JH, Choy JC, Kim RW, Kirkiles-Smith N, Maher SE, Karras JG, Bennett CF, Bothwell AL, Pober JS, Tellides G. Interferon-γ Induces X-linked Inhibitor of Apoptosis-associated Factor-1 and Noxa Expression and Potentiates Human Vascular Smooth Muscle Cell Apoptosis by STAT3 Activation*. Journal Of Biological Chemistry 2008, 283: 6832-6842. PMID: 18192275, DOI: 10.1074/jbc.m706021200.Peer-Reviewed Original ResearchMeSH KeywordsAdaptor Proteins, Signal TransducingAnimalsApoptosisApoptosis Regulatory ProteinsF-Box ProteinsGene Expression RegulationHumansInterferon-gammaIntracellular Signaling Peptides and ProteinsMiceModels, BiologicalMuscle, Smooth, VascularNeoplasm ProteinsProto-Oncogene Proteins c-bcl-2Signal TransductionSTAT3 Transcription FactorTissue TransplantationConceptsVascular smooth muscle cellsInhibitor of apoptosisHuman vascular smooth muscle cellsSTAT3 activationNoxa expressionFactor 1Mouse vascular smooth muscle cellsExpression of XAF1Vascular smooth muscle cell apoptosisSmooth muscle cell apoptosisMuscle cell apoptosisApoptotic stimuliTranscription factorsTranscription (STAT) proteinsGene productsPro-apoptotic effectsHuman coronary artery graftsSignal transducerDeath receptorsMicroarray analysisHuman endothelial cellsChimeric animal modelPhenotypic modulationSTAT1 activationNuclear translocation
2007
Interferon-&ggr; Induces Human Vascular Smooth Muscle Cell Proliferation and Intimal Expansion by Phosphatidylinositol 3-Kinase–Dependent Mammalian Target of Rapamycin Raptor Complex 1 Activation
Wang Y, Bai Y, Qin L, Zhang P, Yi T, Teesdale SA, Zhao L, Pober JS, Tellides G. Interferon-&ggr; Induces Human Vascular Smooth Muscle Cell Proliferation and Intimal Expansion by Phosphatidylinositol 3-Kinase–Dependent Mammalian Target of Rapamycin Raptor Complex 1 Activation. Circulation Research 2007, 101: 560-569. PMID: 17656678, DOI: 10.1161/circresaha.107.151068.Peer-Reviewed Original ResearchMeSH KeywordsAdaptor Proteins, Signal TransducingAdenoviridaeAnimalsAortaCell ProliferationCells, CulturedChromonesCoronary Artery DiseaseCoronary VesselsEnzyme InhibitorsGene Transfer TechniquesGenetic VectorsGraft RejectionHumansHyperplasiaImmunosuppressive AgentsInterferon-gammaMechanistic Target of Rapamycin Complex 1MiceMice, SCIDMorpholinesMultiprotein ComplexesMuscle, Smooth, VascularMyocytes, Smooth MusclePhosphatidylinositol 3-KinasesPhosphoinositide-3 Kinase InhibitorsPhosphorylationProteinsRegulatory-Associated Protein of mTORRibosomal Protein S6 Kinases, 70-kDaSirolimusTime FactorsTissue Culture TechniquesTOR Serine-Threonine KinasesTranscription FactorsTransplantation, HeterologousTunica IntimaConceptsVascular smooth muscle cellsVascular smooth muscle cell proliferationS6 kinase 1 activationSmooth muscle cellsRibosomal protein S6 kinase 1Mammalian targetProtein S6 kinase 1Muscle cellsS6 kinase 1Smooth muscle cell proliferationMTORC1 inhibitor rapamycinMuscle cell proliferationCell proliferationKinase 1 activationIntimal expansionFurther mechanistic insightsHuman vascular smooth muscle cell proliferationHuman coronary artery graftsKinase 1Species specificityInhibitor rapamycinSerum-free conditionsCell growthCellular proliferationImmunodeficient mouse recipients
2005
Recruitment of CXCR3+ and CCR5+ T Cells and Production of Interferon-γ-Inducible Chemokines in Rejecting Human Arteries
Burns WR, Wang Y, Tang PC, Ranjbaran H, Iakimov A, Kim J, Cuffy M, Bai Y, Pober JS, Tellides G. Recruitment of CXCR3+ and CCR5+ T Cells and Production of Interferon-γ-Inducible Chemokines in Rejecting Human Arteries. American Journal Of Transplantation 2005, 5: 1226-1236. PMID: 15888026, DOI: 10.1111/j.1600-6143.2005.00892.x.Peer-Reviewed Original ResearchMeSH KeywordsAntineoplastic AgentsBlood VesselsCells, CulturedChemokine CCL4Chemokine CCL5Chemokine CXCL10Chemokine CXCL11Chemokine CXCL9Chemokines, CXCEndothelial CellsGraft RejectionHeart TransplantationHumansIntercellular Signaling Peptides and ProteinsInterferon-gammaLeukocytesMacrophage Inflammatory ProteinsMuscle, Smooth, VascularReceptors, CCR5Receptors, ChemokineReceptors, CXCR3Reverse Transcriptase Polymerase Chain ReactionRNA, MessengerT-LymphocytesTransplantation, HomologousVascular DiseasesConceptsT cellsIFN-gamma-secreting T cellsClinical allograft rejectionRecruitment of CXCR3Allogeneic T cellsVascular smooth muscle cellsExpression of chemokinesCoronary artery segmentsProduction of interferonDifferent vascular compartmentsSmooth muscle cellsReal-time RT-PCRImmunodeficient mouse hostsAcute rejectionAllograft rejectionInducible chemokinesMicrovascular inflammationConduit arteriesIP-10MIP-1betaImmunological privilegeTh1 cellsChemokine mRNAChemokine receptorsI-TAC