2022
Not all well-differentiated cutaneous squamous cell carcinomas are equal: Tumors with disparate biologic behavior have differences in protein expression via digital spatial profiling
Vesely M, Martinez-Morilla S, Gehlhausen JR, McNiff JM, Whang PG, Rimm D, Ko CJ. Not all well-differentiated cutaneous squamous cell carcinomas are equal: Tumors with disparate biologic behavior have differences in protein expression via digital spatial profiling. Journal Of The American Academy Of Dermatology 2022, 87: 695-698. PMID: 35398219, DOI: 10.1016/j.jaad.2022.03.057.Peer-Reviewed Original ResearchExamination of Low ERBB2 Protein Expression in Breast Cancer Tissue
Fernandez AI, Liu M, Bellizzi A, Brock J, Fadare O, Hanley K, Harigopal M, Jorns JM, Kuba MG, Ly A, Podoll M, Rabe K, Sanders MA, Singh K, Snir OL, Soong TR, Wei S, Wen H, Wong S, Yoon E, Pusztai L, Reisenbichler E, Rimm DL. Examination of Low ERBB2 Protein Expression in Breast Cancer Tissue. JAMA Oncology 2022, 8: 1-4. PMID: 35113160, PMCID: PMC8814969, DOI: 10.1001/jamaoncol.2021.7239.Peer-Reviewed Original ResearchConceptsBreast cancer biopsiesT-DXdCancer biopsiesLarge randomized clinical trialsRandomized clinical trialsERBB2 protein expressionCentral pathology laboratoryBreast cancer tissuesAmerican Pathologists surveysStudy of concordanceTrastuzumab deruxtecanERBB2 positivityPatient populationClinical trialsScore 0Breast cancerImmunohistochemistry scoreCancer tissuesIHC assaysPatientsPathology laboratoryProtein expressionBiopsyIHCConcordance
2021
BRCA1 Protein Expression Predicts Survival in Glioblastoma Patients from an NRG Oncology RTOG Cohort
Vassilakopoulou M, Won M, Curran WJ, Souhami L, Prados MD, Langer CJ, Rimm DL, Hanna JA, Neumeister VM, Melian E, Diaz AZ, Atkins JN, Komarnicky LT, Schultz CJ, Howard SP, Zhang P, Dicker AP, Knisely JPS. BRCA1 Protein Expression Predicts Survival in Glioblastoma Patients from an NRG Oncology RTOG Cohort. Oncology 2021, 99: 580-588. PMID: 33957633, PMCID: PMC8491475, DOI: 10.1159/000516168.Peer-Reviewed Original ResearchConceptsBRCA1 protein expressionTensin homolog (PTEN) tumor suppressor geneProtein expressionTumor suppressor geneQuantitative protein analysisDNA repairGenetic profiling studiesMolecular markersSuppressor geneProtein analysisProfiling studiesBRCA1 expressionSitu hybridizationExpression levelsTumor formationCommon malignant brain tumorCancer cellsTissue microarrayGlioblastoma tumorsExpressionPre-temozolomide eraGlioblastoma patientsP33.02 Comparison of PD-L1 Protein Expression Between Primary and Metastatic Lesions in Lung Cancer Patients
Moutafi M, Tao W, Huang R, Haberberger J, Alexander B, Ramkissoon S, Ross J, Syrigos K, Wei W, Pusztai L, Rimm D, Vathiotis I. P33.02 Comparison of PD-L1 Protein Expression Between Primary and Metastatic Lesions in Lung Cancer Patients. Journal Of Thoracic Oncology 2021, 16: s405-s406. DOI: 10.1016/j.jtho.2021.01.671.Peer-Reviewed Original Research
2020
PD-L1 Protein Expression on Both Tumor Cells and Macrophages are Associated with Response to Neoadjuvant Durvalumab with Chemotherapy in Triple-negative Breast Cancer
Ahmed FS, Gaule P, McGuire J, Patel K, Blenman K, Pusztai L, Rimm DL. PD-L1 Protein Expression on Both Tumor Cells and Macrophages are Associated with Response to Neoadjuvant Durvalumab with Chemotherapy in Triple-negative Breast Cancer. Clinical Cancer Research 2020, 26: 5456-5461. PMID: 32709714, PMCID: PMC7572612, DOI: 10.1158/1078-0432.ccr-20-1303.Peer-Reviewed Original ResearchMeSH KeywordsAdultAgedAntibodies, MonoclonalAntigens, CDAntigens, Differentiation, MyelomonocyticAntineoplastic Combined Chemotherapy ProtocolsB7-H1 AntigenBiomarkers, TumorCell ProliferationFemaleGene Expression Regulation, NeoplasticHumansLymphocytes, Tumor-InfiltratingMacrophagesMiddle AgedNeoadjuvant TherapyProgrammed Cell Death 1 ReceptorTriple Negative Breast NeoplasmsConceptsTriple-negative breast cancerPD-L1 expressionNeoadjuvant durvalumabTumor cellsImmune cellsBreast cancerPretreatment core-needle biopsiesPhase I/II clinical trialsPD-L1 protein expressionIMpassion 130 trialCore needle biopsyAmount of CD68Neoadjuvant settingMetastatic settingPD-L1Clinical trialsNeedle biopsyInsufficient tissuePatientsCD68Stromal compartmentQuantitative immunofluorescenceChemotherapyFinal analysisProtein expressionAntibody 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 Research
2019
High-Plex Predictive Marker Discovery for Melanoma Immunotherapy–Treated Patients Using Digital Spatial Profiling
Toki MI, Merritt CR, Wong PF, Smithy JW, Kluger HM, Syrigos KN, Ong GT, Warren SE, Beechem JM, Rimm DL. High-Plex Predictive Marker Discovery for Melanoma Immunotherapy–Treated Patients Using Digital Spatial Profiling. Clinical Cancer Research 2019, 25: 5503-5512. PMID: 31189645, PMCID: PMC6744974, DOI: 10.1158/1078-0432.ccr-19-0104.Peer-Reviewed Original ResearchMeSH KeywordsAntineoplastic Agents, ImmunologicalBiomarkers, TumorFemaleFluorescent Antibody TechniqueHumansImmunohistochemistryImmunotherapyLymphocytes, Tumor-InfiltratingMaleMelanomaMolecular Diagnostic TechniquesMolecular Targeted TherapyPrognosisProportional Hazards ModelsTissue Array AnalysisTreatment OutcomeConceptsNon-small cell lung cancerProlonged progression-free survivalDigital spatial profilingOverall survivalPD-L1Predictive markerPD-L1 expressionProgression-free survivalProtein expressionCell lung cancerNovel predictive markerCD68-positive cellsStromal CD3Melanoma immunotherapyImmune markersImmune therapyPrognostic valueLung cancerAntibody cocktailTissue microarrayQuantitative fluorescenceOutcome assessmentTumor cellsHigh concordanceMultiple biomarkersQuantitative assessments and clinical outcomes in HER2 equivocal 2018 ASCO/CAP ISH group 4 breast cancer
Gupta S, Neumeister V, McGuire J, Song YS, Acs B, Ho K, Weidler J, Wong W, Rhees B, Bates M, Rimm DL, Bossuyt V. Quantitative assessments and clinical outcomes in HER2 equivocal 2018 ASCO/CAP ISH group 4 breast cancer. Npj Breast Cancer 2019, 5: 28. PMID: 31482108, PMCID: PMC6715641, DOI: 10.1038/s41523-019-0122-x.Peer-Reviewed Original ResearchBreast cancerQuantitative immunofluorescenceIHC 0/1Systemic treatmentRT-qPCRClinical Oncology/CollegeAdditional outcome informationProtein expressionReal-time quantitative reverse transcription polymerase chain reactionHER2 protein levelsQuantitative reverse transcription polymerase chain reactionReverse transcription-polymerase chain reactionTranscription-polymerase chain reactionASCO/CAP recommendationsRNA/protein expressionQIF scoresPatient characteristicsClinical outcomesTrastuzumab treatmentSurvival outcomesPolymerase chain reactionIHC 2Treatment decisionsCAP recommendationsPatients
2018
CD68, CD163, and matrix metalloproteinase 9 (MMP-9) co-localization in breast tumor microenvironment predicts survival differently in ER-positive and -negative cancers
Pelekanou V, Villarroel-Espindola F, Schalper KA, Pusztai L, Rimm DL. CD68, CD163, and matrix metalloproteinase 9 (MMP-9) co-localization in breast tumor microenvironment predicts survival differently in ER-positive and -negative cancers. Breast Cancer Research 2018, 20: 154. PMID: 30558648, PMCID: PMC6298021, DOI: 10.1186/s13058-018-1076-x.Peer-Reviewed Original ResearchMeSH KeywordsAntigens, CDAntigens, Differentiation, MyelomonocyticAntineoplastic AgentsBiomarkers, TumorBreastBreast NeoplasmsDisease-Free SurvivalFemaleGene Expression Regulation, NeoplasticHumansMacrophagesMatrix Metalloproteinase 9Middle AgedPatient SelectionPrognosisReceptors, Cell SurfaceReceptors, EstrogenRetrospective StudiesSurvival AnalysisTissue Array AnalysisTumor MicroenvironmentConceptsTumor-associated macrophagesOverall survivalQuantitative immunofluorescenceMacrophage markersBreast cancerHigh expressionPan-macrophage marker CD68Triple-negative breast cancerCD163/CD68Multiplexed quantitative immunofluorescenceImproved overall survivalProtein expressionWorse overall survivalPoor overall survivalMMP-9 protein expressionSubclass of patientsMacrophage-targeted therapiesMatrix metalloproteinase-9Tissue microarray formatMMP-9 proteinBreast tumor microenvironmentModulator of responseParaffin-embedded tissuesBreast cancer biomarkersCohort B
2017
Effect of neoadjuvant chemotherapy on tumor-infiltrating lymphocytes and PD-L1 expression in breast cancer and its clinical significance
Pelekanou V, Carvajal-Hausdorf DE, Altan M, Wasserman B, Carvajal-Hausdorf C, Wimberly H, Brown J, Lannin D, Pusztai L, Rimm DL. Effect of neoadjuvant chemotherapy on tumor-infiltrating lymphocytes and PD-L1 expression in breast cancer and its clinical significance. Breast Cancer Research 2017, 19: 91. PMID: 28784153, PMCID: PMC5547502, DOI: 10.1186/s13058-017-0884-8.Peer-Reviewed Original ResearchConceptsStromal tumor-infiltrating lymphocytesPD-L1 expressionTumor-infiltrating lymphocytesRecurrence-free survivalNeoadjuvant chemotherapyResidual cancer tissueTIL countBreast cancerCancer tissuesDeath ligand 1 (PD-L1) protein expressionNode-positive breast cancerImproved recurrence-free survivalPD-L1 protein expressionHigher TIL countsPD-L1 statusProtein expressionBreast cancer patientsBreast cancer tissuesPost-treatment samplesPrechemotherapy samplesTIL infiltrationResidual cancerImmune markersResidual diseasePatient cohortP2.01-046 Quantitative Measurement of B7-H3 Protein Expression and Its Association with B7-H4, PD-L1 and TILs in NSCLC Topic: Immune Mechanisms in Thoracic Cancer and Targeted Therapy
Altan M, Pelekanou V, Schalper K, Toki M, Herbst R, Rimm D. P2.01-046 Quantitative Measurement of B7-H3 Protein Expression and Its Association with B7-H4, PD-L1 and TILs in NSCLC Topic: Immune Mechanisms in Thoracic Cancer and Targeted Therapy. Journal Of Thoracic Oncology 2017, 12: s813-s814. DOI: 10.1016/j.jtho.2016.11.1098.Peer-Reviewed Original Research
2016
PD-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 ResearchConceptsPD-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 1PatientsCancerExpressionTrialsQuantitative 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
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
2013
Expression of Drug Targets in Patients Treated with Sorafenib, Carboplatin and Paclitaxel
Jilaveanu LB, Zhao F, Zito CR, Kirkwood JM, Nathanson KL, D'Andrea K, Wilson M, Rimm DL, Flaherty KT, Lee SJ, Kluger HM. Expression of Drug Targets in Patients Treated with Sorafenib, Carboplatin and Paclitaxel. PLOS ONE 2013, 8: e69748. PMID: 23936348, PMCID: PMC3735539, DOI: 10.1371/journal.pone.0069748.Peer-Reviewed Original ResearchConceptsProgression-free survivalOverall survivalVEGF-R1FGF-R1Paclitaxel-based therapyVEGF-R1 expressionPre-treatment tumorsPredictive biomarker signaturesMultitarget kinase inhibitorPDGF-RβSitu protein expressionTherapeutic ratioTaxane sensitivityMitogen-activated protein kinase pathwayPatientsVEGF-R3CarboplatinSorafenibVEGF-R2C-kitKinase inhibitorsTherapyProtein expressionPhase IIISorafenib targets
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 methodHypoxia-induced protein CAIX is associated with somatic loss of BRCA1 protein and pathway activity in triple negative breast cancer
Neumeister VM, Sullivan CA, Lindner R, Lezon-Geyda K, Li J, Zavada J, Martel M, Glazer PM, Tuck DP, Rimm DL, Harris L. Hypoxia-induced protein CAIX is associated with somatic loss of BRCA1 protein and pathway activity in triple negative breast cancer. Breast Cancer Research And Treatment 2012, 136: 67-75. PMID: 22976806, DOI: 10.1007/s10549-012-2232-0.Peer-Reviewed Original ResearchMeSH KeywordsAdultAgedAged, 80 and overAntigens, NeoplasmBiomarkers, TumorBRCA1 ProteinBreast NeoplasmsCarbonic Anhydrase IXCarbonic AnhydrasesCell HypoxiaFemaleGene Expression Regulation, NeoplasticHumansMiddle AgedMutationNeoplasm StagingReceptor, ErbB-2Receptors, EstrogenReceptors, ProgesteroneSignal TransductionConceptsTriple-negative breast cancerCA IX protein expressionNegative breast cancerBreast cancer cohortTNBC cohortProtein expressionBreast cancerCancer cohortCA IXTriple-negative patientsWorse overall survivalBreast cancer patientsTriple-negative phenotypePARP inhibitor therapyUnselected breast cancer cohortGene expression signaturesInhibitor therapyNegative patientsOverall survivalUnselected cohortCancer patientsBRCA1 protein expressionUseful biomarkerPatientsDefective homologous recombination
2011
P1-07-03: Preanalytical Variables Affect Protein Expression in Formalin Fixed Paraffin Embedded Tissue – Assessment of Intrinsic Controls To Define Tissue Quality for Immunohistochemical Analysis.
Neumeister V, Lostritto K, Siddiqui S, Anagnostou V, Vassilakopoulou M, Zarrella E, Molinaro A, Hicks D, Rimm D. P1-07-03: Preanalytical Variables Affect Protein Expression in Formalin Fixed Paraffin Embedded Tissue – Assessment of Intrinsic Controls To Define Tissue Quality for Immunohistochemical Analysis. Cancer Research 2011, 71: p1-07-03-p1-07-03. DOI: 10.1158/0008-5472.sabcs11-p1-07-03.Peer-Reviewed Original ResearchIschemic timeProtein expressionBreast cancerFormalin fixationDifferent breast cancer cohortsTumor tissuePairs of biopsiesTumor heterogeneityBreast cancer cohortBreast cancer biopsiesBreast cancer specimenPre-analytical variablesHistone 4ER alphaCancer cohortImmunohistochemical analysisCancer biopsiesSecond cohortAQUA scoreCancer specimenClinical settingQuantitative immunofluorescenceResectionCancer ResBiopsyStandardization of Epidermal Growth Factor Receptor (EGFR) Measurement by Quantitative Immunofluorescence and Impact on Antibody-Based Mutation Detection in Non–Small Cell Lung Cancer
Dimou A, Agarwal S, Anagnostou V, Viray H, Christensen S, Rothberg B, Zolota V, Syrigos K, Rimm DL. Standardization of Epidermal Growth Factor Receptor (EGFR) Measurement by Quantitative Immunofluorescence and Impact on Antibody-Based Mutation Detection in Non–Small Cell Lung Cancer. American Journal Of Pathology 2011, 179: 580-589. PMID: 21722621, PMCID: PMC3157192, DOI: 10.1016/j.ajpath.2011.04.031.Peer-Reviewed Original ResearchConceptsNon-small cell lung cancerCell lung cancerPrognostic valueMutation-specific antibodiesLung cancerQuantitative immunofluorescenceEpidermal growth factor receptor (EGFR) protein expressionIndependent NSCLC cohortsPopulation-based cohortEGFR mutation rateReceptor protein expressionTotal proteinFalse-positive casesPrediction of responseWestern blot analysisNSCLC cohortRetrospective cohortReceptor measurementsYale cohortEGFR expressionCohortEGFRAQUA technologyProtein expressionAntibodies
2010
Evaluation of the incidence and prognostic value of mutant epidermal growth factor receptor (EGFRvIII) protein expression in head and neck squamous cell carcinomas (HNSCC) using AQUA.
Pectasides E, Fountzilas G, Kountourakis P, Gouveris P, Sasaki C, Duffey D, Rimm D, Burtness B, Psyrri D. Evaluation of the incidence and prognostic value of mutant epidermal growth factor receptor (EGFRvIII) protein expression in head and neck squamous cell carcinomas (HNSCC) using AQUA. Journal Of Clinical Oncology 2010, 28: 5538-5538. DOI: 10.1200/jco.2010.28.15_suppl.5538.Peer-Reviewed Original Research