2023
Multi-Institutional Study of Pathologist Reading of the Programmed Cell Death Ligand-1 Combined Positive Score Immunohistochemistry Assay for Gastric or Gastroesophageal Junction Cancer
Fernandez A, Robbins C, Gaule P, Agostini-Vulaj D, Anders R, Bellizzi A, Chen W, Chen Z, Gopal P, Zhao L, Lisovsky M, Liu X, Shia J, Wang H, Yang Z, McCann L, Chan Y, Weidler J, Bates M, Zhang X, Rimm D. Multi-Institutional Study of Pathologist Reading of the Programmed Cell Death Ligand-1 Combined Positive Score Immunohistochemistry Assay for Gastric or Gastroesophageal Junction Cancer. Modern Pathology 2023, 36: 100128. PMID: 36889057, PMCID: PMC10198879, DOI: 10.1016/j.modpat.2023.100128.Peer-Reviewed Original ResearchMeSH KeywordsApoptosisB7-H1 AntigenBiomarkers, TumorEsophageal NeoplasmsEsophagogastric JunctionHumansImmunohistochemistryLigandsPathologistsReproducibility of ResultsStomach NeoplasmsConceptsOverall percent agreementCut pointsReal-world settingHigher cut pointsCell death ligand 1Percent agreementGastroesophageal junction cancerPD-L1 immunohistochemistryDeath ligand 1Companion diagnostic testsMessenger RNA measurementsJunction cancerCancer casesImmunohistochemistry assaysIHC resultsDrug AdministrationPredictive valueScoring systemRange of assaysDiagnostic testsInstitutional studyRNA measurementsImmunohistochemistryPoor specificityPathologist's readingMulti-institutional Assessment of Pathologist Scoring HER2 Immunohistochemistry
Robbins C, Fernandez A, Han G, Wong S, Harigopal M, Podoll M, Singh K, Ly A, Kuba M, Wen H, Sanders M, Brock J, Wei S, Fadare O, Hanley K, Jorns J, Snir O, Yoon E, Rabe K, Soong T, Reisenbichler E, Rimm D. Multi-institutional Assessment of Pathologist Scoring HER2 Immunohistochemistry. Modern Pathology 2023, 36: 100032. PMID: 36788069, PMCID: PMC10278086, DOI: 10.1016/j.modpat.2022.100032.Peer-Reviewed Original ResearchMeSH KeywordsBiomarkers, TumorBreast NeoplasmsFemaleGenes, erbB-2HumansImmunohistochemistryIn Situ Hybridization, FluorescencePathologistsReceptor, ErbB-2Reproducibility of ResultsConceptsOverall percent agreementHuman epidermal growth factor 2HER2 IHCReal-world settingEpidermal growth factor 2HER2-negative statusBreast cancer biopsiesCompanion diagnostic testsMulti-institutional assessmentGrowth factor 2Breast cancerImmunohistochemistry assaysCancer biopsiesHER2 immunohistochemistryPathologist concordanceIHCClinical standardsPercent agreementDiagnostic testsSubstantial discordanceERBB2 geneInterrater reliabilityPathologistsFactor 2Concordance
2021
Determination of the number of observers needed to evaluate a subjective test and its application in two PD‐L1 studies
Han G, Schell MJ, Reisenbichler ES, Guo B, Rimm DL. Determination of the number of observers needed to evaluate a subjective test and its application in two PD‐L1 studies. Statistics In Medicine 2021, 41: 1361-1375. PMID: 34897773, PMCID: PMC10243718, DOI: 10.1002/sim.9282.Peer-Reviewed Original ResearchB7-H1 AntigenCorrelation of DataHumansImmunohistochemistryObserver VariationReproducibility of Results
2020
Antibody validation for protein expression on tissue slides: a protocol for immunohistochemistry
MacNeil T, Vathiotis IA, Martinez-Morilla S, Yaghoobi V, Zugazagoitia J, Liu Y, Rimm DL. Antibody validation for protein expression on tissue slides: a protocol for immunohistochemistry. BioTechniques 2020, 69: 460-468. PMID: 32852223, PMCID: PMC7807291, DOI: 10.2144/btn-2020-0095.Peer-Reviewed Original ResearchMeSH KeywordsAntibodiesHumansImmunohistochemistryReproducibility of ResultsSubcellular FractionsTissue FixationProspective multi-institutional evaluation of pathologist assessment of PD-L1 assays for patient selection in triple negative breast cancer
Reisenbichler ES, Han G, Bellizzi A, Bossuyt V, Brock J, Cole K, Fadare O, Hameed O, Hanley K, Harrison BT, Kuba MG, Ly A, Miller D, Podoll M, Roden AC, Singh K, Sanders MA, Wei S, Wen H, Pelekanou V, Yaghoobi V, Ahmed F, Pusztai L, Rimm DL. Prospective multi-institutional evaluation of pathologist assessment of PD-L1 assays for patient selection in triple negative breast cancer. Modern Pathology 2020, 33: 1746-1752. PMID: 32300181, PMCID: PMC8366569, DOI: 10.1038/s41379-020-0544-x.Peer-Reviewed Original ResearchConceptsTriple-negative breast cancerNegative breast cancerOverall percent agreementPD-L1Intraclass correlation coefficientBreast cancerAdvanced triple-negative breast cancerPD-L1 positive casesImmune cell stainingMultiple pathologistsPD-L1 scoringMulti-institutional evaluationLung cancer studiesAtezolizumab therapySP142 assaySP263 assaysPatient selectionSP263SP142US FoodDrug AdministrationPathologist's assessmentPositive casesReal-world settingPercent agreementDigital quantitative assessment of PD-L1 using digital spatial profiling
Gupta S, Zugazagoitia J, Martinez-Morilla S, Fuhrman K, Rimm DL. Digital quantitative assessment of PD-L1 using digital spatial profiling. Laboratory Investigation 2020, 100: 1311-1317. PMID: 32249818, PMCID: PMC7502436, DOI: 10.1038/s41374-020-0424-5.Peer-Reviewed Original ResearchMeSH KeywordsB7-H1 AntigenBiomarkersCell LineHumansImmunohistochemistryProtein Array AnalysisReproducibility of ResultsTissue Array AnalysisConceptsTissue microarrayPD-L1Digital spatial profilingDeath 1 ligand 1 expressionPD-L1 immunohistochemistry assaysDigital quantitative assessmentDigital Spatial ProfilerLigand 1 expressionPD-L1 assaysCompanion diagnostic testingCell linesImmune therapyPredictive markerImmune cellsImmunohistochemistry assaysQuantitative immunohistochemistryUS FoodDrug AdministrationDiagnostic testingImmunohistochemistryNCounter platformTumor cellsDifferent scoring methodsMultiple studiesDifferent antibodies
2019
False-positive pathology: improving reproducibility with the next generation of pathologists
Mazer BL, Homer RJ, Rimm DL. False-positive pathology: improving reproducibility with the next generation of pathologists. Laboratory Investigation 2019, 99: 1260-1265. PMID: 31019290, DOI: 10.1038/s41374-019-0257-2.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 ResearchMeSH KeywordsAdultAgedAged, 80 and overBreast NeoplasmsCohort StudiesHumansImage Processing, Computer-AssistedKi-67 AntigenMiddle AgedObserver VariationReproducibility of ResultsConceptsDIA platformsAn 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 ResearchMeSH KeywordsBiomarkers, TumorBreast NeoplasmsFemaleHumansImage Processing, Computer-AssistedImmunohistochemistryKi-67 AntigenReproducibility of ResultsConceptsIntraclass 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 scoreCancerA dormant TIL phenotype defines non-small cell lung carcinomas sensitive to immune checkpoint blockers
Gettinger SN, Choi J, Mani N, Sanmamed MF, Datar I, Sowell R, Du VY, Kaftan E, Goldberg S, Dong W, Zelterman D, Politi K, Kavathas P, Kaech S, Yu X, Zhao H, Schlessinger J, Lifton R, Rimm DL, Chen L, Herbst RS, Schalper KA. A dormant TIL phenotype defines non-small cell lung carcinomas sensitive to immune checkpoint blockers. Nature Communications 2018, 9: 3196. PMID: 30097571, PMCID: PMC6086912, DOI: 10.1038/s41467-018-05032-8.Peer-Reviewed Original ResearchMeSH KeywordsAmino Acid SequenceAnimalsAntibodies, BlockingCarcinogenesisCarcinoma, Non-Small-Cell LungCell ProliferationCytotoxicity, ImmunologicHistocompatibility Antigens Class IHumansLung NeoplasmsLymphocyte ActivationLymphocytes, Tumor-InfiltratingMaleMice, Inbred NODMice, SCIDMutant ProteinsMutationPeptidesPhenotypeProgrammed Cell Death 1 ReceptorReproducibility of ResultsSurvival AnalysisTobaccoConceptsImmune checkpoint blockersCheckpoint blockersQuantitative immunofluorescenceNon-small cell lung carcinoma patientsCell lung carcinoma patientsNon-small cell lung carcinomaPatient-derived xenograft modelsIntratumoral T cellsMultiplexed quantitative immunofluorescencePD-1 blockadeLevels of CD3Lung carcinoma patientsCell lung carcinomaT cell proliferationPre-treatment samplesTIL phenotypeSurvival benefitCarcinoma patientsEffector capacityLung carcinomaT cellsWhole-exome DNA sequencingXenograft modelFavorable responseBlockersMacrodissection 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 markers
2017
High concordance of a closed-system, RT-qPCR breast cancer assay for HER2 mRNA, compared to clinically determined immunohistochemistry, fluorescence in situ hybridization, and quantitative immunofluorescence
Wasserman BE, Carvajal-Hausdorf DE, Ho K, Wong W, Wu N, Chu VC, Lai EW, Weidler JM, Bates M, Neumeister V, Rimm DL. High concordance of a closed-system, RT-qPCR breast cancer assay for HER2 mRNA, compared to clinically determined immunohistochemistry, fluorescence in situ hybridization, and quantitative immunofluorescence. Laboratory Investigation 2017, 97: 1521-1526. PMID: 28892092, PMCID: PMC5711560, DOI: 10.1038/labinvest.2017.93.Peer-Reviewed Original ResearchConceptsInvasive breast cancerBreast cancerQuantitative immunofluorescenceRT-qPCRFormalin-fixed paraffin-embedded tissue blocksRT-qPCR assaysEquivocal categoryReal-time quantitative reverse transcription polymerase chain reactionHER2 receptor statusQuantitative reverse transcription polymerase chain reactionParaffin-embedded tissue blocksReverse transcription-polymerase chain reactionTranscription-polymerase chain reactionIHC/FISHMRNA measurementsAssessment of HER2Low-resource settingsReceptor statusPolymerase chain reactionPathology reportsCT cutsSingle-use cartridgeResource settingsHER2 mRNATissue blocksA Prospective, Multi-institutional, Pathologist-Based Assessment of 4 Immunohistochemistry Assays for PD-L1 Expression in Non–Small Cell Lung Cancer
Rimm DL, Han G, Taube JM, Yi ES, Bridge JA, Flieder DB, Homer R, West WW, Wu H, Roden AC, Fujimoto J, Yu H, Anders R, Kowalewski A, Rivard C, Rehman J, Batenchuk C, Burns V, Hirsch FR, Wistuba II. A Prospective, Multi-institutional, Pathologist-Based Assessment of 4 Immunohistochemistry Assays for PD-L1 Expression in Non–Small Cell Lung Cancer. JAMA Oncology 2017, 3: 1051-1058. PMID: 28278348, PMCID: PMC5650234, DOI: 10.1001/jamaoncol.2017.0013.Peer-Reviewed Original ResearchMeSH KeywordsAntibodiesB7-H1 AntigenBiological AssayCarcinoma, Non-Small-Cell LungHumansImmunohistochemistryLung NeoplasmsPathologistsReproducibility of ResultsConceptsPD-L1 expressionNon-small cell lung cancerDako Link 48 platformIntraclass correlation coefficientCell lung cancerImmune cellsPD-L1Tumor cellsSP142 antibodyLung cancerAnti-programmed cell death 1Less PD-L1 expressionCell death ligand 1Tumour cell assessmentPD-L1 antibodiesDeath ligand 1Cell death 1Cell scoringOwn scoring systemSerial histologic sectionsSP142 assayL1 therapyDeath-1Laboratory-developed testsPatient responseProof of the quantitative potential of immunofluorescence by mass spectrometry
Toki MI, Cecchi F, Hembrough T, Syrigos KN, Rimm DL. Proof of the quantitative potential of immunofluorescence by mass spectrometry. Laboratory Investigation 2017, 97: 329-334. PMID: 28092364, PMCID: PMC5334147, DOI: 10.1038/labinvest.2016.148.Peer-Reviewed Original Research
2016
Quantitative and pathologist-read comparison of the heterogeneity of programmed death-ligand 1 (PD-L1) expression in non-small cell lung cancer
Rehman JA, Han G, Carvajal-Hausdorf DE, Wasserman BE, Pelekanou V, Mani NL, McLaughlin J, Schalper KA, Rimm DL. Quantitative and pathologist-read comparison of the heterogeneity of programmed death-ligand 1 (PD-L1) expression in non-small cell lung cancer. Modern Pathology 2016, 30: 340-349. PMID: 27834350, PMCID: PMC5334264, DOI: 10.1038/modpathol.2016.186.Peer-Reviewed Original ResearchMeSH KeywordsAgedCarcinoma, Non-Small-Cell LungFemaleHumansImmunohistochemistryLung NeoplasmsMaleProgrammed Cell Death 1 ReceptorReproducibility of ResultsConceptsPD-L1 expressionPD-L1Immune cellsImmune cell PD-L1 expressionNon-small cell lung cancerNon-small cell lung cancer (NSCLC) casesCell lung cancer casesTumor cellsPD-L1 assessmentStromal immune cellsPD-L1 positivityCell lung cancerLung cancer patientsLung cancer casesRepresentative tumor areasPathologist scoresLikelihood of responseConcordance correlation coefficientRabbit monoclonal antibodyIntraclass correlation coefficientCancer patientsLung cancerImmunohistochemistry slidesCancer casesTumor tissueA proposal for validation of antibodies
Uhlen M, Bandrowski A, Carr S, Edwards A, Ellenberg J, Lundberg E, Rimm DL, Rodriguez H, Hiltke T, Snyder M, Yamamoto T. A proposal for validation of antibodies. Nature Methods 2016, 13: 823-827. PMID: 27595404, PMCID: PMC10335836, DOI: 10.1038/nmeth.3995.Peer-Reviewed Original ResearchQuantitative assessment of the spatial heterogeneity of tumor-infiltrating lymphocytes in breast cancer
Mani NL, Schalper KA, Hatzis C, Saglam O, Tavassoli F, Butler M, Chagpar AB, Pusztai L, Rimm DL. Quantitative assessment of the spatial heterogeneity of tumor-infiltrating lymphocytes in breast cancer. Breast Cancer Research 2016, 18: 78. PMID: 27473061, PMCID: PMC4966732, DOI: 10.1186/s13058-016-0737-x.Peer-Reviewed Original ResearchConceptsIntraclass correlation coefficientQuantitative immunofluorescenceBreast cancerSame cancerSingle biopsyMultiplexed quantitative immunofluorescenceTumor-infiltrating lymphocytesPotential predictive markerPrimary breast carcinomaCytokeratin-positive epithelial cellsCD20-positive lymphocytesCD8 levelsLymphocyte scoreQIF scoresLymphocyte countLymphocyte subpopulationsMultiple biopsiesSubpopulation countsPredictive markerPrognostic informationBreast carcinomaBiopsyB lymphocytesCD3Breast tumors[Letter to the Editor] The need for improved education and training in research antibody usage and validation practices
Freedman LP, Gibson MC, Bradbury AR, Buchberg AM, Davis D, Dolled-Filhart MP, Lund-Johansen F, Rimm DL. [Letter to the Editor] The need for improved education and training in research antibody usage and validation practices. BioTechniques 2016, 61: 16-18. PMID: 27401669, DOI: 10.2144/000114431.Peer-Reviewed Original ResearchAutomated measurement of estrogen receptor in breast cancer: a comparison of fluorescent and chromogenic methods of measurement
Zarrella ER, Coulter M, Welsh AW, Carvajal DE, Schalper KA, Harigopal M, Rimm D, Neumeister V. Automated measurement of estrogen receptor in breast cancer: a comparison of fluorescent and chromogenic methods of measurement. Laboratory Investigation 2016, 96: 1016-1025. PMID: 27348626, PMCID: PMC5008858, DOI: 10.1038/labinvest.2016.73.Peer-Reviewed Original ResearchQuantitative Assessment of the Heterogeneity of PD-L1 Expression in Non–Small-Cell Lung Cancer
McLaughlin J, Han G, Schalper KA, Carvajal-Hausdorf D, Pelakanou V, Rehman J, Velcheti V, Herbst R, LoRusso P, Rimm DL. Quantitative Assessment of the Heterogeneity of PD-L1 Expression in Non–Small-Cell Lung Cancer. JAMA Oncology 2016, 2: 1-9. PMID: 26562159, PMCID: PMC4941982, DOI: 10.1001/jamaoncol.2015.3638.Peer-Reviewed Original ResearchMeSH KeywordsAgedAntibodies, MonoclonalAntibody SpecificityB7-H1 AntigenBiomarkers, TumorCarcinoma, Non-Small-Cell LungFemaleFluorescent Antibody TechniqueHumansImmunohistochemistryLung NeoplasmsMaleObserver VariationPredictive Value of TestsReproducibility of ResultsRetrospective StudiesTissue Array AnalysisConceptsTumor-infiltrating lymphocytesPD-L1 expressionPD-L1 antibodiesPD-L1 protein expressionCell lung cancerPD-L1Whole tissue sectionsQuantitative immunofluorescenceLung cancerChromogenic immunohistochemistryPoor concordanceDifferent PD-L1 antibodiesHigh tumor-infiltrating lymphocytesTumor PD-L1 expressionPD-L1 protein levelsCell lung cancer biopsiesMonoclonal antibodiesCurrent consensus guidelinesProtein expressionDurable clinical responsesMain outcome measuresEarly phase trialsLung cancer biopsiesRabbit monoclonal antibodyCorresponding tissue microarrays