2023
Multiplex Immunohistochemistry and Immunofluorescence: A Practical Update for Pathologists
Harms P, Frankel T, Moutafi M, Rao A, Rimm D, Taube J, Thomas D, Chan M, Pantanowitz L. Multiplex Immunohistochemistry and Immunofluorescence: A Practical Update for Pathologists. Modern Pathology 2023, 36: 100197. PMID: 37105494, DOI: 10.1016/j.modpat.2023.100197.Peer-Reviewed Original ResearchConceptsDigital spatial profilingMost clinical laboratoriesTumor microenvironmentImmunofluorescence/immunohistochemistryImmuno-oncology researchDiagnostic practiceClinical laboratoriesRoutine diagnostic useAntitumor immunityAdvanced cancerImmune populationsMultiplex stainingEosin stainingIHC stainsPractical updateClinical diagnostic practiceMultiplex immunohistochemistrySingle biomarkerImmunohistochemistryMultiplexed immunohistochemistryStandardized protocolChromogenic immunohistochemistryDiagnostic useMultiple biomarkersSerial sections
2021
Quantitative Image Analysis for Tissue Biomarker Use: A White Paper From the Digital Pathology Association
Lara H, Li Z, Abels E, Aeffner F, Bui MM, ElGabry EA, Kozlowski C, Montalto MC, Parwani AV, Zarella MD, Bowman D, Rimm D, Pantanowitz L. Quantitative Image Analysis for Tissue Biomarker Use: A White Paper From the Digital Pathology Association. Applied Immunohistochemistry & Molecular Morphology 2021, 29: 479-493. PMID: 33734106, PMCID: PMC8354563, DOI: 10.1097/pai.0000000000000930.Peer-Reviewed Original Research
2020
Digital 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 ResearchConceptsTissue 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
Multiplex Quantitative Analysis of Tumor-Infiltrating Lymphocytes and Immunotherapy Outcome in Metastatic Melanoma
Wong PF, Wei W, Smithy JW, Acs B, Toki MI, Blenman K, Zelterman D, Kluger HM, Rimm DL. Multiplex Quantitative Analysis of Tumor-Infiltrating Lymphocytes and Immunotherapy Outcome in Metastatic Melanoma. Clinical Cancer Research 2019, 25: 2442-2449. PMID: 30617133, PMCID: PMC6467753, DOI: 10.1158/1078-0432.ccr-18-2652.Peer-Reviewed Original ResearchMeSH KeywordsAgedAged, 80 and overAntineoplastic Agents, ImmunologicalBiomarkersBiomarkers, TumorFemaleFluorescent Antibody TechniqueHumansImmunohistochemistryImmunotherapyKaplan-Meier EstimateLymphocytes, Tumor-InfiltratingMaleMelanomaMiddle AgedMolecular Targeted TherapyNeoplasm StagingROC CurveT-Lymphocyte SubsetsConceptsCell countTIL activationQuantitative immunofluorescenceLymphocytic infiltrationMelanoma patientsMetastatic melanomaAnti-PD-1 responseAnti-PD-1 therapyCell death 1 (PD-1) inhibitionAbsence of immunotherapyDeath-1 (PD-1) inhibitionDisease control rateProgression-free survivalCD8 cell countsTumor-Infiltrating LymphocytesNew predictive biomarkersWhole tissue sectionsRECIST 1.1Progressive diseaseDurable responsesObjective responsePartial responseImmunotherapy outcomesLymphocyte profilesMultivariable analysis
2016
Quantitative 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 tumorsPD-L1 Expression in Lung Cancer
Yu H, Boyle TA, Zhou C, Rimm D, Hirsch FR. PD-L1 Expression in Lung Cancer. Journal Of Thoracic Oncology 2016, 11: 964-975. PMID: 27117833, PMCID: PMC5353357, DOI: 10.1016/j.jtho.2016.04.014.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsB7-H1 AntigenBiomarkersHumansImmunohistochemistryImmunotherapyLung NeoplasmsMiceConceptsPD-L1Lung cancerAnti-PD-1 drugsDifferent PD-L1 antibodiesPD-L1 protein expressionImmunotherapy clinical trialsAdvanced lung cancerPD-L1 expressionPD-L1 antibodiesSubset of patientsDeath ligand 1PD-L1 detectionBetter patient careClinical trialsPatient careProtein expressionHistory of useImmunohistochemistry platformBiomarkersImmunotherapyLigand 1PatientsCancerExpressionTrialsRAS/MAPK Activation Is Associated with Reduced Tumor-Infiltrating Lymphocytes in Triple-Negative Breast Cancer: Therapeutic Cooperation Between MEK and PD-1/PD-L1 Immune Checkpoint Inhibitors
Loi S, Dushyanthen S, Beavis PA, Salgado R, Denkert C, Savas P, Combs S, Rimm DL, Giltnane JM, Estrada MV, Sánchez V, Sanders ME, Cook RS, Pilkinton MA, Mallal SA, Wang K, Miller VA, Stephens PJ, Yelensky R, Doimi FD, Gómez H, Ryzhov SV, Darcy PK, Arteaga CL, Balko JM. RAS/MAPK Activation Is Associated with Reduced Tumor-Infiltrating Lymphocytes in Triple-Negative Breast Cancer: Therapeutic Cooperation Between MEK and PD-1/PD-L1 Immune Checkpoint Inhibitors. Clinical Cancer Research 2016, 22: 1499-1509. PMID: 26515496, PMCID: PMC4794351, DOI: 10.1158/1078-0432.ccr-15-1125.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsB7-H1 AntigenBiomarkersCell Line, TumorDisease Models, AnimalDisease ProgressionFemaleGene Expression ProfilingHumansImmunomodulationImmunophenotypingLymphocytes, Tumor-InfiltratingMiceMitogen-Activated Protein KinasesMortalityPhenotypeProgrammed Cell Death 1 ReceptorProtein Kinase InhibitorsRas ProteinsSignal TransductionTranscriptomeTriple Negative Breast NeoplasmsConceptsTriple-negative breast cancerTumor-infiltrating lymphocytesImmune checkpoint inhibitorsResidual diseaseNeoadjuvant chemotherapyBreast cancerPD-L1Checkpoint inhibitorsMHC expressionMouse modelPD-1/PD-L1 immune checkpoint inhibitorsPD-L1 immune checkpoint inhibitorsPresence of TILsPD-1/PD-L1Low tumor-infiltrating lymphocytesPD-L1/PDAntitumor immune responseRAS/MAPK activationCell-surface MHC expressionMAPK activationImproved survivalImproved prognosisPredictive biomarkersClinical trialsImmune response
2011
Quantitative 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
2009
Activated Wnt/ß-catenin signaling in melanoma is associated with decreased proliferation in patient tumors and a murine melanoma model
Chien AJ, Moore EC, Lonsdorf AS, Kulikauskas RM, Rothberg BG, Berger AJ, Major MB, Hwang ST, Rimm DL, Moon RT. Activated Wnt/ß-catenin signaling in melanoma is associated with decreased proliferation in patient tumors and a murine melanoma model. Proceedings Of The National Academy Of Sciences Of The United States Of America 2009, 106: 1193-1198. PMID: 19144919, PMCID: PMC2626610, DOI: 10.1073/pnas.0811902106.Peer-Reviewed Original ResearchConceptsBeta-catenin signalingNormal melanocyte developmentTranscriptional profiling revealsWnt/beta-catenin signalingMelanoma cellsUp-regulates genesWnt/ß-cateninMelanoma progressionSmall molecule activatorsRole of WntMelanocyte developmentCell fateTranscriptional changesB16 murine melanoma cellsCellular differentiationProfiling revealsMelanocyte differentiationMelanoma cell linesMurine melanoma cellsß-cateninHuman melanoma cell linesWnt3aMurine melanoma modelCell linesReduced expression
2007
Dr. David Rimm is interviewed by Feras Akbik.
Rimm D. Dr. David Rimm is interviewed by Feras Akbik. The Yale Journal Of Biology And Medicine 2007, 80: 183-5. PMID: 18449386, PMCID: PMC2347361.Peer-Reviewed Original ResearchQuantitative Measurement of Epidermal Growth Factor Receptor Is a Negative Predictive Factor for Tamoxifen Response in Hormone Receptor–Positive Premenopausal Breast Cancer
Giltnane JM, Rydén L, Cregger M, Bendahl PO, Jirström K, Rimm DL. Quantitative Measurement of Epidermal Growth Factor Receptor Is a Negative Predictive Factor for Tamoxifen Response in Hormone Receptor–Positive Premenopausal Breast Cancer. Journal Of Clinical Oncology 2007, 25: 3007-3014. PMID: 17634479, DOI: 10.1200/jco.2006.08.9938.Peer-Reviewed Original ResearchMeSH KeywordsAdultAgedBiomarkersBiopsy, NeedleBreast NeoplasmsDrug Resistance, NeoplasmErbB ReceptorsEstrogen AntagonistsFemaleHumansImmunohistochemistryMiddle AgedMultivariate AnalysisPredictive Value of TestsPremenopauseProbabilityProportional Hazards ModelsReceptors, EstrogenRisk AssessmentSensitivity and SpecificitySurvival AnalysisTamoxifenConceptsEpidermal growth factor receptorER-positive patientsEGFR expressionBreast cancerEstrogen receptorTamoxifen-treated patientsEarly breast cancerRecurrence-free survivalRandomized clinical trialsLow EGFR expressionSignificant beneficial effectAdjuvant tamoxifenGrowth factor receptorEndocrine therapyTamoxifen responseTamoxifen treatmentClinical trialsSitu protein expressionUntreated groupTissue microarrayPatientsBeneficial effectsProtein expressionFactor receptorTreatment effects
2006
Immunohistochemistry and quantitative analysis of protein expression.
Cregger M, Berger AJ, Rimm DL. Immunohistochemistry and quantitative analysis of protein expression. Archives Of Pathology & Laboratory Medicine 2006, 130: 1026-30. PMID: 16831029, DOI: 10.5858/2006-130-1026-iaqaop.Peer-Reviewed Original Research
2004
Molecular markers for prognosis after isolated postmastectomy chest wall recurrence
Haffty BG, Hauser A, Choi DH, Parisot N, Rimm D, King B, Carter D. Molecular markers for prognosis after isolated postmastectomy chest wall recurrence. Cancer 2004, 100: 252-263. PMID: 14716758, DOI: 10.1002/cncr.11915.Peer-Reviewed Original ResearchConceptsHER-2/neu statusChest wall recurrencePositive HER-2/neu statusLocal-regional controlLocal recurrenceNeu statusDistant metastasisPR statusProgesterone receptorBreast carcinomaDistant metastasis-free survival ratesLocal chest wall recurrenceDistant metastasis-free rateMetastasis-free survival ratesHER-2/neuLymph node recurrencePositive PR statusProgression-free rateSimultaneous distant metastasesOperable breast carcinomaLocal-regional recurrenceMetastasis-free ratePostmastectomy chest wallExternal beam radiotherapyLong-term survival
2003
Tissue microarray analysis of signal transducers and activators of transcription 3 (Stat3) and phospho-Stat3 (Tyr705) in node-negative breast cancer shows nuclear localization is associated with a better prognosis.
Dolled-Filhart M, Camp RL, Kowalski DP, Smith BL, Rimm DL. Tissue microarray analysis of signal transducers and activators of transcription 3 (Stat3) and phospho-Stat3 (Tyr705) in node-negative breast cancer shows nuclear localization is associated with a better prognosis. Clinical Cancer Research 2003, 9: 594-600. PMID: 12576423.Peer-Reviewed Original ResearchMeSH KeywordsAcute-Phase ProteinsBiomarkersBreast NeoplasmsCell NucleusDNA-Binding ProteinsFemaleHumansImmunohistochemistryLymphatic MetastasisMultivariate AnalysisPhosphorylationPhosphotyrosinePrognosisProportional Hazards ModelsSTAT3 Transcription FactorSurvival AnalysisTime FactorsTrans-ActivatorsConceptsNode-negative breast cancerBreast cancerCytoplasmic expressionNuclear expressionOverall survivalReceptor stainingPrognostic markerPhospho-STAT3Breast cancer tissue microarrayEstrogen receptor stainingProgesterone receptor stainingNode-negative tumorsLarge retrospective studyIndependent prognostic markerBreast cancer specimensTissue microarray analysisCancer tissue microarrayShort-term survivalTranscription 3Breast cancer tumorsHER2 stainingBetter prognosisRetrospective studyRole of STAT3Signal transducer