2023
Immune dysfunction revealed by digital spatial profiling of immuno-oncology markers in progressive stages of renal cell carcinoma and in brain metastases
Schoenfeld D, Moutafi M, Martinez S, Djureinovic D, Merkin R, Adeniran A, Braun D, Signoretti S, Choueiri T, Parisi F, Hurwitz M, Rimm D, Wei W, Jilaveanu L, Kluger H. Immune dysfunction revealed by digital spatial profiling of immuno-oncology markers in progressive stages of renal cell carcinoma and in brain metastases. Journal For ImmunoTherapy Of Cancer 2023, 11: e007240. PMID: 37586773, PMCID: PMC10432651, DOI: 10.1136/jitc-2023-007240.Peer-Reviewed Original ResearchConceptsRenal cell carcinomaBrain metastasesPrimary tumorTumor microenvironmentDigital spatial profilingCell carcinomaActivation protein expressionInflammatory macrophage markersRCC brain metastasesInnate immune activatorsNormal kidney samplesProgressive stagesExtracranial metastasesTim-3Immune checkpointsImmune dysfunctionImmune activationRCC metastasisLonger survivalImmune activatorsMacrophage markersTreatment responseSeparate cohortTissue microarrayMetastatic samples
2022
Location matters: LAG3 levels are lower in renal cell carcinoma metastatic sites compared to primary tumors, and expression at metastatic sites only may have prognostic importance
Schoenfeld D, Merkin R, Moutafi M, Martinez S, Adeniran A, Kumar D, Jilaveanu L, Hurwitz M, Rimm D, Kluger H. Location matters: LAG3 levels are lower in renal cell carcinoma metastatic sites compared to primary tumors, and expression at metastatic sites only may have prognostic importance. Frontiers In Oncology 2022, 12: 990367. PMID: 36313654, PMCID: PMC9608089, DOI: 10.3389/fonc.2022.990367.Peer-Reviewed Original ResearchRenal cell carcinomaImmune checkpoint inhibitorsMetastatic sitesBrain metastasesPrimary tumorMechanisms of resistancePD-1/PD-L1Anti-PD-1 therapyHigh-risk clinical characteristicsLarger primary tumor sizeAdvanced renal cell carcinomaAlternative immune checkpointsCertain drug regimensPoor-risk diseasePD-1 inhibitorsMinority of patientsPrimary tumor sizeLonger overall survivalGrade 4 tumorsProtein levelsPrimary RCC tumorsAttractive therapeutic targetIdentification of subgroupsCheckpoint inhibitorsUpfront therapyCECR2 drives breast cancer metastasis by promoting NF-κB signaling and macrophage-mediated immune suppression
Zhang M, Liu ZZ, Aoshima K, Cai WL, Sun H, Xu T, Zhang Y, An Y, Chen JF, Chan LH, Aoshima A, Lang SM, Tang Z, Che X, Li Y, Rutter SJ, Bossuyt V, Chen X, Morrow JS, Pusztai L, Rimm DL, Yin M, Yan Q. CECR2 drives breast cancer metastasis by promoting NF-κB signaling and macrophage-mediated immune suppression. Science Translational Medicine 2022, 14: eabf5473. PMID: 35108062, PMCID: PMC9003667, DOI: 10.1126/scitranslmed.abf5473.Peer-Reviewed Original ResearchConceptsBreast cancer metastasisReticuloendotheliosis viral oncogene homolog ACancer metastasisImmune suppressionM2 macrophagesWorse metastasis-free survivalMetastatic breast cancerMetastasis-free survivalV-rel avian reticuloendotheliosis viral oncogene homolog ACancer-related deathPrimary breast tumorsMultiple mouse modelsNF-κB signalingImmunocompetent settingNuclear factor-κB family membersMetastasis-promoting genesDistant metastasisMetastatic sitesPrimary tumorEffective therapyBreast cancerMetastasis treatmentMouse modelBreast tumorsMetastasis
2021
Comparison of programmed death-ligand 1 protein expression between primary and metastatic lesions in patients with lung cancer
Moutafi MK, Tao W, Huang R, Haberberger J, Alexander B, Ramkissoon S, Ross JS, Syrigos K, Wei W, Pusztai L, Rimm DL, Vathiotis IA. Comparison of programmed death-ligand 1 protein expression between primary and metastatic lesions in patients with lung cancer. Journal For ImmunoTherapy Of Cancer 2021, 9: e002230. PMID: 33833050, PMCID: PMC8039214, DOI: 10.1136/jitc-2020-002230.Peer-Reviewed Original ResearchConceptsPD-L1 expressionMetastatic lesionsLung cancer casesLung cancerCancer casesAdvanced stage non-small cell lung cancerNon-small cell lung cancerNon-squamous histologyCell lung cancerFuture patient managementDefinite diagnostic testSquamous histologyFoundation MedicineLymph nodesRoutine careHistologic subtypeMetastatic sitesPrimary lesionRetrospective studyAdrenal glandPrimary tumorPleural fluidPatient managementTrial designDrug Administration
2020
Comparison of PD-L1 protein expression between primary tumors and metastatic lesions in triple negative breast cancers
Rozenblit M, Huang R, Danziger N, Hegde P, Alexander B, Ramkissoon S, Blenman K, Ross JS, Rimm DL, Pusztai L. Comparison of PD-L1 protein expression between primary tumors and metastatic lesions in triple negative breast cancers. Journal For ImmunoTherapy Of Cancer 2020, 8: e001558. PMID: 33239417, PMCID: PMC7689582, DOI: 10.1136/jitc-2020-001558.Peer-Reviewed Original ResearchConceptsPD-L1 positivity ratePD-L1 positivityPD-L1 expressionDifferent metastatic sitesPrimary tumorMetastatic sitesPositivity rateImmune cellsMetastatic lesionsTumor cellsPD-L1 protein expressionTriple-negative breast cancerMore primary tumorsTriple negative breast cancer tumorsPrimary breast lesionsPrimary outcome measureSoft tissueNegative breast cancerLow positivity rateBreast cancer tumorsBone metastasesFoundation MedicineLymph nodesPD-L1Spearman correlation coefficient
2018
Immunological differences between primary and metastatic breast cancer
Szekely B, Bossuyt V, Li X, Wali VB, Patwardhan GA, Frederick C, Silber A, Park T, Harigopal M, Pelekanou V, Zhang M, Yan Q, Rimm DL, Bianchini G, Hatzis C, Pusztai L. Immunological differences between primary and metastatic breast cancer. Annals Of Oncology 2018, 29: 2232-2239. PMID: 30203045, DOI: 10.1093/annonc/mdy399.Peer-Reviewed Original ResearchMeSH KeywordsAdolescentAdultAgedAntineoplastic Agents, ImmunologicalB7-H1 AntigenBiomarkers, TumorBiopsyBreast NeoplasmsDisease ProgressionDrug Resistance, NeoplasmFemaleGene Expression RegulationHumansImmunologic SurveillanceLymphocyte CountLymphocytes, Tumor-InfiltratingMiddle AgedMutation RateTumor EscapeTumor MicroenvironmentYoung AdultConceptsMetastatic breast cancerBreast cancerTherapeutic targetToll-like receptor pathway genesImmuno-oncology therapeutic targetsBreast cancer evolvesImmune proteasome expressionPD-L1 positivityCorresponding primary tumorsPotential therapeutic targetMHC class IImmune-related genesMetastatic cancer samplesLigand/receptor pairLymphocyte countT helperT-regsPD-L1Immune microenvironmentCytotoxic TPrimary tumorMastoid cellsDisease progressionTherapeutic combinationsMacrophage markers
2016
Non-malignant respiratory epithelial cells preferentially proliferate from resected non-small cell lung cancer specimens cultured under conditionally reprogrammed conditions
Gao B, Huang C, Kernstine K, Pelekanou V, Kluger Y, Jiang T, Peters-Hall JR, Coquelin M, Girard L, Zhang W, Huffman K, Oliver D, Kinose F, Haura E, Teer JK, Rix U, Le AT, Aisner DL, Varella-Garcia M, Doebele RC, Covington KR, Hampton OA, Doddapaneni HV, Jayaseelan JC, Hu J, Wheeler DA, Shay JW, Rimm DL, Gazdar A, Minna JD. Non-malignant respiratory epithelial cells preferentially proliferate from resected non-small cell lung cancer specimens cultured under conditionally reprogrammed conditions. Oncotarget 2016, 5: 11114-11126. PMID: 28052041, PMCID: PMC5355251, DOI: 10.18632/oncotarget.14366.Peer-Reviewed Original ResearchMeSH KeywordsA549 CellsAdultAgedAged, 80 and overBase SequenceCarcinoma, Non-Small-Cell LungCell Line, TumorCell ProliferationCells, CulturedCoculture TechniquesDNA Copy Number VariationsDNA Mutational AnalysisEpithelial CellsFemaleGene Expression ProfilingGenetic Predisposition to DiseaseHumansLung NeoplasmsMaleMiddle AgedMutationRespiratory MucosaTumor Cells, CulturedConceptsNon-small cell lung cancerRespiratory epithelial cellsNon-malignant lungCell lung cancerCRC culturesLung cancerEpithelial cellsResected non-small cell lung cancerPrimary lung cancerNon-malignant samplesLung epithelial cellsRho-kinase inhibitorNon-malignant cellsPrimary NSCLCPrimary tumorDiploid patternOriginal tumorTumor specimensTumor tissueTumorsKinase inhibitorsCancerCancer cellsMRNA expression profilesSmall subpopulation
2013
Marginal and Joint Distributions of S100, HMB-45, and Melan-A Across a Large Series of Cutaneous Melanomas
Viray H, Bradley WR, Schalper KA, Rimm DL, Rothberg BE. Marginal and Joint Distributions of S100, HMB-45, and Melan-A Across a Large Series of Cutaneous Melanomas. Archives Of Pathology & Laboratory Medicine 2013, 137: 1063-73. PMID: 23899062, PMCID: PMC3963468, DOI: 10.5858/arpa.2012-0284-oa.Peer-Reviewed Original ResearchConceptsHMB-45Primary tumorCutaneous melanomaLarge seriesMelanoma-specific survivalMelanoma primary tumorsGroup of antigensLarge tissue microarrayClinicopathologic covariatesClinicopathologic criteriaPrognostic relevanceHistopathologic profileClinicopathologic correlatesAntigen expressionClinicopathologic parametersMelanoma markersTissue microarrayPositive expressionSurvival analysisMelanomaMelanS100Melanoma cellsBivariate associationsSignificant differences
2011
Gefitinib or Placebo in Combination with Tamoxifen in Patients with Hormone Receptor–Positive Metastatic Breast Cancer: A Randomized Phase II Study
Osborne CK, Neven P, Dirix LY, Mackey JR, Robert J, Underhill C, Schiff R, Gutierrez C, Migliaccio I, Anagnostou VK, Rimm DL, Magill P, Sellers M. Gefitinib or Placebo in Combination with Tamoxifen in Patients with Hormone Receptor–Positive Metastatic Breast Cancer: A Randomized Phase II Study. Clinical Cancer Research 2011, 17: 1147-1159. PMID: 21220480, PMCID: PMC3074404, DOI: 10.1158/1078-0432.ccr-10-1869.Peer-Reviewed Original ResearchMeSH KeywordsAdultAgedAged, 80 and overAntineoplastic Agents, HormonalAntineoplastic Combined Chemotherapy ProtocolsBiomarkers, TumorBreast NeoplasmsDrug-Related Side Effects and Adverse ReactionsErbB ReceptorsFemaleGefitinibHumansMiddle AgedNeoplasms, Hormone-DependentPlacebosQuinazolinesReceptor, ErbB-2Receptors, EstrogenSignal TransductionTamoxifenTreatment OutcomeConceptsAdjuvant aromatase inhibitorsMetastatic breast cancerBreast cancerHormone receptor-positive metastatic breast cancerPositive metastatic breast cancerRandomized phase II studyRandomized phase II trialClinical benefit ratePhase II studyPhase II trialProgression-free survivalStratum 1Epidermal growth factor receptor inhibitor gefitinibFurther investigationAdjuvant tamoxifenImproved PFSPFS HRAI therapyII studyII trialMetastatic diseaseAppropriate patientsPredictive biomarkersPrimary tumorTamoxifen resistance
2009
Molecular Classification of Normal and Cancer Mammospheres.
Agarwal S, Camp R, Lannin D, Halligan K, Stern D, Tuck D, Harris L, Rimm D. Molecular Classification of Normal and Cancer Mammospheres. Cancer Research 2009, 69: 501-501. DOI: 10.1158/0008-5472.sabcs-09-501.Peer-Reviewed Original ResearchCancer stem cellsPrimary tumorBreast cancerTumor cellsStem cellsAbsence of CD24Breast cancer specimensHuman breast cancerFine-needle aspirationNormal breast tissueExpression of CD44Tumor tissue samplesPutative stem cell markersCD44-positive cellsKey protein markersEx vivo cultureStem cell markersNovel drug targetsSpecific therapyTreatment successNeedle aspirationCancer specimensMyoepithelial markersBT-20Positive cells
2005
Automated Quantitative Analysis of Activator Protein-2α Subcellular Expression in Melanoma Tissue Microarrays Correlates with Survival Prediction
Berger AJ, Davis DW, Tellez C, Prieto VG, Gershenwald JE, Johnson MM, Rimm DL, Bar-Eli M. Automated Quantitative Analysis of Activator Protein-2α Subcellular Expression in Melanoma Tissue Microarrays Correlates with Survival Prediction. Cancer Research 2005, 65: 11185-11192. PMID: 16322269, DOI: 10.1158/0008-5472.can-05-2300.Peer-Reviewed Original ResearchConceptsAP-2 expressionM.D. Anderson Cancer CenterCytoplasmic expression levelsAnderson Cancer CenterAP-2 levelsProgression of melanomaMelanoma tissue microarrayClinicopathologic factorsRetrospective cohortMetastatic groupPrognostic significanceBreslow depthCancer CenterNevi groupPoor prognosisMetastatic melanomaPrimary tumorPrimary melanomaDiagnosis groupsTissue microarrayTumor growthMelanoma specimensMalignant transformationHuman melanomaMelanoma progressionAltered Localization of p120 Catenin During Epithelial to Mesenchymal Transition of Colon Carcinoma Is Prognostic for Aggressive Disease
Bellovin DI, Bates RC, Muzikansky A, Rimm DL, Mercurio AM. Altered Localization of p120 Catenin During Epithelial to Mesenchymal Transition of Colon Carcinoma Is Prognostic for Aggressive Disease. Cancer Research 2005, 65: 10938-10945. PMID: 16322241, DOI: 10.1158/0008-5472.can-05-1947.Peer-Reviewed Original ResearchConceptsSurvival timeMesenchymal transitionLymph node metastasisColorectal cancer progressionPoor patient outcomesE-cadherinLate-stage tumorsPatient survival timePost-EMT cellsP120ctn expressionAltered localizationLymph nodesNode metastasisAggressive diseaseTumor stagePrimary tumorTumor necrosisColorectal carcinomaPatient outcomesColon carcinoma cellsE-cadherin lossCytoplasmic stainingColon carcinomaCancer progressionCarcinoma cellsHypercalcemia of Malignancy due to Ectopic Transactivation of the Parathyroid Hormone Gene
VanHouten JN, Yu N, Rimm D, Dotto J, Arnold A, Wysolmerski JJ, Udelsman R. Hypercalcemia of Malignancy due to Ectopic Transactivation of the Parathyroid Hormone Gene. The Journal Of Clinical Endocrinology & Metabolism 2005, 91: 580-583. PMID: 16263810, DOI: 10.1210/jc.2005-2095.Peer-Reviewed Original ResearchMeSH KeywordsAgedDNA MethylationDNA, NeoplasmFatal OutcomeFemaleGene ExpressionHumansHypercalcemiaHyperparathyroidismNeuroendocrine TumorsPancreatic NeoplasmsParathyroid GlandsParathyroid Hormone-Related ProteinPromoter Regions, GeneticReverse Transcriptase Polymerase Chain ReactionTranscriptional ActivationUsing a Xenograft Model of Human Breast Cancer Metastasis to Find Genes Associated with Clinically Aggressive Disease
Kluger HM, Lev D, Kluger Y, McCarthy MM, Kiriakova G, Camp RL, Rimm DL, Price JE. Using a Xenograft Model of Human Breast Cancer Metastasis to Find Genes Associated with Clinically Aggressive Disease. Cancer Research 2005, 65: 5578-5587. PMID: 15994930, DOI: 10.1158/0008-5472.can-05-0108.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsBreast NeoplasmsCell AdhesionCell Growth ProcessesCell Line, TumorDisease Models, AnimalFemaleGene Expression ProfilingHumansImmunohistochemistryMiceMice, NudeMultivariate AnalysisNeoplasm InvasivenessNeoplasm MetastasisNeoplasm TransplantationOligonucleotide Array Sequence AnalysisPredictive Value of TestsReproducibility of ResultsTissue Array AnalysisTransplantation, HeterologousConceptsBreast cancerXenograft modelHuman breast cancer metastasisLymph node involvementLymph node metastasisChemokine ligand 1Human breast cancer cell linesBreast cancer metastasisLeukocyte protease inhibitorBreast cancer cell linesBreast cancer tissuesHSP-70 expressionHeat shock protein 70Cancer cell linesShock protein 70Identification of genesNode involvementNode metastasisAggressive diseaseClinicopathologic variablesPrimary tumorPrognostic markerNovel therapiesCDNA microarray analysisCancer tissuesAutomated Quantitative Analysis of E-Cadherin Expression in Lymph Node Metastases Is Predictive of Survival in Invasive Ductal Breast Cancer
Harigopal M, Berger AJ, Camp RL, Rimm DL, Kluger HM. Automated Quantitative Analysis of E-Cadherin Expression in Lymph Node Metastases Is Predictive of Survival in Invasive Ductal Breast Cancer. Clinical Cancer Research 2005, 11: 4083-4089. PMID: 15930343, DOI: 10.1158/1078-0432.ccr-04-2191.Peer-Reviewed Original ResearchConceptsE-cadherin expressionLymph node metastasisNodal metastasisBreast cancerImproved survivalNode metastasisTissue microarrayNode-positive breast cancerInvasive ductal breast cancerHER2/neu statusAnti-invasive roleInvasive ductal tumorsNode-positive patientsDuctal breast cancerSubset of patientsGood prognostic markerAggressive tumor behaviorStrong E-cadherin expressionHigh E-cadherin expressionCy5-conjugated antibodiesDuctal tumorsMetastatic sitesPrognostic valueTumor sizePrimary tumorβ1,6-Branched Oligosaccharides Are Increased in Lymph Node Metastases and Predict Poor Outcome in Breast Carcinoma
Handerson T, Camp R, Harigopal M, Rimm D, Pawelek J. β1,6-Branched Oligosaccharides Are Increased in Lymph Node Metastases and Predict Poor Outcome in Breast Carcinoma. Clinical Cancer Research 2005, 11: 2969-2973. PMID: 15837749, DOI: 10.1158/1078-0432.ccr-04-2211.Peer-Reviewed Original ResearchConceptsLymph node metastasisPrimary tumorNode metastasisPoor outcomeBreast carcinomaNode-positive primary tumorsPatient-matched primary tumorsNode-negative tumorsBreast carcinoma metastasisPatient ageNodal metastasisTumor sizeRisk factorsNuclear gradeCarcinoma metastasisTissue microarrayBlinded observersMyeloid cellsMetastasisMultivariate analysisTumor progressionTumorsSystemic migrationCancer cellsLectin histochemistry
2001
Novel inactivating mutations of transforming growth factor‐β type I receptor gene in head‐and‐neck cancer metastases
Chen T, Yan W, Wells R, Rimm D, McNiff J, Leffell D, Reiss M. Novel inactivating mutations of transforming growth factor‐β type I receptor gene in head‐and‐neck cancer metastases. International Journal Of Cancer 2001, 93: 653-661. PMID: 11477574, DOI: 10.1002/ijc.1381.Peer-Reviewed Original ResearchMeSH KeywordsActivin Receptors, Type IAmino Acid SequenceDisease ProgressionEndoplasmic ReticulumFemaleHead and Neck NeoplasmsHumansMaleMolecular Sequence DataMutationNeoplasms, Glandular and EpithelialNeoplasms, Unknown PrimaryProtein Serine-Threonine KinasesReceptor, Transforming Growth Factor-beta Type IReceptors, Transforming Growth Factor betaSequence Homology, Amino AcidSignal TransductionTransforming Growth Factor betaConceptsT beta RNeck cancer metastasisTGF-beta signalingCancer metastasisBeta RTGF betaBeta signalingLate-stage diseaseHuman epithelial neoplasmsCorresponding primary tumorsBreast cancer metastasisFine needle aspiratesTGF-beta type I receptorNovel inactivating mutationsBeta type I receptorType I receptorStage diseaseCarcinoma cell linesPrimary tumorCell cycle arrestEpithelial neoplasmsCodon 387MetastasisI receptorHuman tumors