2022
CECR2 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
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 ResearchMeSH KeywordsAdultAgedAged, 80 and overB7-H1 AntigenFemaleHumansMiddle AgedNeoplasm MetastasisRetrospective StudiesTriple Negative Breast NeoplasmsConceptsPD-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
2019
Spatial Architecture and Arrangement of Tumor-Infiltrating Lymphocytes for Predicting Likelihood of Recurrence in Early-Stage Non–Small Cell Lung Cancer
Corredor G, Wang X, Zhou Y, Lu C, Fu P, Syrigos K, Rimm DL, Yang M, Romero E, Schalper KA, Velcheti V, Madabhushi A. Spatial Architecture and Arrangement of Tumor-Infiltrating Lymphocytes for Predicting Likelihood of Recurrence in Early-Stage Non–Small Cell Lung Cancer. Clinical Cancer Research 2019, 25: 1526-1534. PMID: 30201760, PMCID: PMC6397708, DOI: 10.1158/1078-0432.ccr-18-2013.Peer-Reviewed Original Research
2018
Quantitative Spatial Profiling of PD-1/PD-L1 Interaction and HLA-DR/IDO-1 Predicts Improved Outcomes of Anti–PD-1 Therapies in Metastatic Melanoma
Johnson DB, Bordeaux J, Kim J, Vaupel C, Rimm DL, Ho TH, Joseph RW, Daud AI, Conry RM, Gaughan EM, Hernandez-Aya LF, Dimou A, Funchain P, Smithy J, Witte JS, McKee SB, Ko J, Wrangle J, Dabbas B, Tangri S, Lameh J, Hall J, Markowitz J, Balko JM, Dakappagari N. Quantitative Spatial Profiling of PD-1/PD-L1 Interaction and HLA-DR/IDO-1 Predicts Improved Outcomes of Anti–PD-1 Therapies in Metastatic Melanoma. Clinical Cancer Research 2018, 24: 5250-5260. PMID: 30021908, PMCID: PMC6214750, DOI: 10.1158/1078-0432.ccr-18-0309.Peer-Reviewed Original ResearchMeSH KeywordsAdultAgedAntineoplastic Agents, ImmunologicalB7-H1 AntigenBiomarkers, TumorBiopsyCell Line, TumorFemaleHLA-DR AntigensHumansImmunohistochemistryIndoleamine-Pyrrole 2,3,-DioxygenaseMaleMelanomaMiddle AgedModels, BiologicalNeoplasm MetastasisNeoplasm StagingPrognosisProgrammed Cell Death 1 ReceptorProtein BindingRetreatmentTreatment OutcomeConceptsAnti-PD-1 responseHLA-DRValidation cohortPD-1/PD-L1PD-1 blockersPD-1 monotherapyPD-L1 expressionPretreatment tumor biopsiesProgression-free survivalSubset of patientsAcademic cancer centerBiomarkers of responseIndependent validation cohortClin Cancer ResImmunosuppression mechanismsClinical responseOverall survivalPD-L1Melanoma patientsCancer CenterTreatment outcomesTumor biopsiesDiscovery cohortPatientsIndividual biomarkers
2017
Nuclear IRF-1 expression as a mechanism to assess “Capability” to express PD-L1 and response to PD-1 therapy in metastatic melanoma
Smithy JW, Moore LM, Pelekanou V, Rehman J, Gaule P, Wong PF, Neumeister VM, Sznol M, Kluger HM, Rimm DL. Nuclear IRF-1 expression as a mechanism to assess “Capability” to express PD-L1 and response to PD-1 therapy in metastatic melanoma. Journal For ImmunoTherapy Of Cancer 2017, 5: 25. PMID: 28331615, PMCID: PMC5359951, DOI: 10.1186/s40425-017-0229-2.Peer-Reviewed Original ResearchMeSH KeywordsAdultAgedAntibodies, MonoclonalAntibodies, Monoclonal, HumanizedB7-H1 AntigenBiomarkers, PharmacologicalDisease-Free SurvivalFemaleGene Expression Regulation, NeoplasticHumansImmunotherapyInterferon Regulatory Factor-1IpilimumabMaleMelanomaMiddle AgedNeoplasm MetastasisNeoplasms, Second PrimaryNivolumabProgrammed Cell Death 1 ReceptorConceptsProgression-free survivalObjective radiographic responsePD-L1 expressionPD-L1IRF-1 expressionMetastatic melanomaAnti-PD-1 therapyCombination ipilimumab/nivolumabHigh PD-L1 expressionAnti-PD-1 immunotherapyYale-New Haven HospitalIpilimumab/nivolumabPD-1 therapyPR/CRPre-treatment formalinRECIST v1.1 criteriaDeath ligand 1Valuable predictive biomarkerMajor unmet needNew Haven HospitalInterferon regulatory factor 1Combination ipilimumabProgressive diseaseRadiographic responseComplete response
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 mutationsChronogramMutationsEvaluation of PD-L1 Expression and Associated Tumor-Infiltrating Lymphocytes in Laryngeal Squamous Cell Carcinoma
Vassilakopoulou M, Avgeris M, Velcheti V, Kotoula V, Rampias T, Chatzopoulos K, Perisanidis C, Kontos CK, Giotakis AI, Scorilas A, Rimm D, Sasaki C, Fountzilas G, Psyrri A. Evaluation of PD-L1 Expression and Associated Tumor-Infiltrating Lymphocytes in Laryngeal Squamous Cell Carcinoma. Clinical Cancer Research 2016, 22: 704-713. PMID: 26408403, DOI: 10.1158/1078-0432.ccr-15-1543.Peer-Reviewed Original ResearchMeSH KeywordsAdultAgedAged, 80 and overB7-H1 AntigenBiomarkers, TumorCarcinoma, Squamous CellFemaleFollow-Up StudiesGene ExpressionHumansImmunohistochemistryKaplan-Meier EstimateLaryngeal NeoplasmsLymphocytes, Tumor-InfiltratingMaleMiddle AgedNeoplasm GradingNeoplasm MetastasisNeoplasm StagingPrognosisProportional Hazards ModelsRetrospective StudiesRisk FactorsRNA, MessengerConceptsLaryngeal squamous cell carcinomaSquamous cell carcinomaPrimary laryngeal squamous cell carcinomaPD-L1 expressionTumor-infiltrating lymphocytesPD-L1 mRNA expressionTIL densityCell carcinomaAssessment of TILsLaryngeal squamous cell cancerStromal tumor-infiltrating lymphocytesSuperior disease-free survivalTumor PD-L1 expressionMRNA expressionPD-L1 protein expressionPD-L1 mRNA levelsHigher TIL densityImmune checkpoint inhibitorsPD-L1 levelsDisease-free survivalT cell infiltrationSquamous cell cancerSecond independent cohortAdjacent tissue specimensFresh-frozen tumors
2014
In Situ Quantitative Measurement of HER2mRNA Predicts Benefit from Trastuzumab-Containing Chemotherapy in a Cohort of Metastatic Breast Cancer Patients
Vassilakopoulou M, Togun T, Dafni U, Cheng H, Bordeaux J, Neumeister VM, Bobos M, Pentheroudakis G, Skarlos DV, Pectasides D, Kotoula V, Fountzilas G, Rimm DL, Psyrri A. In Situ Quantitative Measurement of HER2mRNA Predicts Benefit from Trastuzumab-Containing Chemotherapy in a Cohort of Metastatic Breast Cancer Patients. PLOS ONE 2014, 9: e99131. PMID: 24968015, PMCID: PMC4072595, DOI: 10.1371/journal.pone.0099131.Peer-Reviewed Original ResearchConceptsBreast cancer patientsMetastatic breast cancer patientsFISH HER2Cancer patientsHER2 mRNAPrognostic factorsTrastuzumab-treated metastatic breast cancer patientsMultivariate Cox regression modelECD HER2Log rank pMetastatic breast cancerStrong prognostic factorCox regression modelKaplan-Meier estimatesHER2 mRNA levelsHER2-ICDChemotherapy regimensMetastatic cohortTrastuzumab treatmentBreast cancerTissue microarrayMRNA statusPerformance of markersHER2 receptorPredictive valueMarkers of Epithelial to Mesenchymal Transition in Association with Survival in Head and Neck Squamous Cell Carcinoma (HNSCC)
Pectasides E, Rampias T, Sasaki C, Perisanidis C, Kouloulias V, Burtness B, Zaramboukas T, Rimm D, Fountzilas G, Psyrri A. Markers of Epithelial to Mesenchymal Transition in Association with Survival in Head and Neck Squamous Cell Carcinoma (HNSCC). PLOS ONE 2014, 9: e94273. PMID: 24722213, PMCID: PMC3983114, DOI: 10.1371/journal.pone.0094273.Peer-Reviewed Original ResearchMeSH KeywordsAutomationBiomarkers, TumorCarcinoma, Squamous CellCohort StudiesEpithelial-Mesenchymal TransitionFemaleGene Expression ProfilingGene Expression Regulation, NeoplasticHead and Neck NeoplasmsHumansImage Processing, Computer-AssistedImmunohistochemistryKaplan-Meier EstimateMaleMultivariate AnalysisNeoplasm MetastasisPhenotypePrognosisProportional Hazards ModelsSquamous Cell Carcinoma of Head and NeckTreatment OutcomeConceptsProgression-free survivalSquamous cell carcinomaOverall survivalCell carcinomaE-cadherinPrimary squamous cell carcinomaNeck squamous cell carcinomaHigh-risk HNSCCKaplan-Meier analysisNovel therapeutic approachesMesenchymal transition phenotypeHigh metastatic potentialLow E-cadherinImproved OSInferior OSIndependent predictorsPoor prognosisCarcinoma prognosisClinicopathological parametersInclusion criteriaTherapeutic approachesTransition phenotypeMetastatic potentialMesenchymal transitionProtein expression analysis
2011
Proinvasion Metastasis Drivers in Early-Stage Melanoma Are Oncogenes
Scott KL, Nogueira C, Heffernan TP, van Doorn R, Dhakal S, Hanna JA, Min C, Jaskelioff M, Xiao Y, Wu CJ, Cameron LA, Perry SR, Zeid R, Feinberg T, Kim M, Woude G, Granter SR, Bosenberg M, Chu GC, DePinho RA, Rimm DL, Chin L. Proinvasion Metastasis Drivers in Early-Stage Melanoma Are Oncogenes. Cancer Cell 2011, 20: 92-103. PMID: 21741599, PMCID: PMC3176328, DOI: 10.1016/j.ccr.2011.05.025.Peer-Reviewed Original ResearchMeSH KeywordsAcid PhosphataseAnimalsCell LineageConserved SequenceEvolution, MolecularGene Expression ProfilingGene Expression Regulation, NeoplasticGenomeHumansIsoenzymesKaplan-Meier EstimateMelanomaMiceNeoplasm InvasivenessNeoplasm MetastasisNeoplasm StagingOncogenesPhosphorylationReproducibility of ResultsSkin NeoplasmsTartrate-Resistant Acid PhosphataseTissue Array AnalysisConceptsFunctional genetic screensGenetic screenGlobal transcriptomeMetastatic potentialSuch genesGenomic evidenceExpression selectionTranscriptomic profilesHuman melanoma tissuesMetastasis driverCell invasionKey pathwaysOncogenic capabilitiesMelanoma tissuesGenesHuman melanomaHuman primary melanomasTranscriptomeMouse modelSpontaneous metastasisOncogeneEnhancerACP5PathwayInvasion
2009
Gab2-Mediated Signaling Promotes Melanoma Metastasis
Horst B, Gruvberger-Saal SK, Hopkins BD, Bordone L, Yang Y, Chernoff KA, Uzoma I, Schwipper V, Liebau J, Nowak NJ, Brunner G, Owens D, Rimm DL, Parsons R, Celebi JT. Gab2-Mediated Signaling Promotes Melanoma Metastasis. American Journal Of Pathology 2009, 174: 1524-1533. PMID: 19342374, PMCID: PMC2671382, DOI: 10.2353/ajpath.2009.080543.Peer-Reviewed Original ResearchMeSH KeywordsAdaptor Proteins, Signal TransducingBiomarkers, TumorBlotting, WesternCell MovementChromosomes, Artificial, BacterialComparative Genomic HybridizationFluorescent Antibody TechniqueGene DosageHumansIn Situ Hybridization, FluorescenceMelanomaNeoplasm InvasivenessNeoplasm MetastasisOligonucleotide Array Sequence AnalysisPolymorphism, Single NucleotideReverse Transcriptase Polymerase Chain ReactionSignal TransductionTissue Array AnalysisConceptsPI3K-Akt pathwayBacterial artificial chromosome array comparative genomic hybridizationInvasive potentialGrowth factor independenceSingle nucleotide polymorphism arrayCritical biological featuresHyperactivation of AKTMelanoma tumor progressionNucleotide polymorphism arrayTumor cell migrationArray comparative genomic hybridizationAdaptor proteinComparative genomic hybridizationRas-ERKFactor independenceMetastatic melanoma samplesMelanoma cell linesGab2Polymorphism arrayCopy numberCell migrationHuman cancersUndefined roleWide searchGenomic hybridization
2008
Prognostic Significance of Cadherin-Based Adhesion Molecules in Cutaneous Malignant Melanoma
Kreizenbeck GM, Berger AJ, Subtil A, Rimm DL, Rothberg BE. Prognostic Significance of Cadherin-Based Adhesion Molecules in Cutaneous Malignant Melanoma. Cancer Epidemiology Biomarkers & Prevention 2008, 17: 949-958. PMID: 18398036, PMCID: PMC3312613, DOI: 10.1158/1055-9965.epi-07-2729.Peer-Reviewed Original Research
2007
The X-linked inhibitor of apoptosis protein (XIAP) is up-regulated in metastatic melanoma, and XIAP cleavage by Phenoxodiol is associated with Carboplatin sensitization
Kluger HM, McCarthy MM, Alvero AB, Sznol M, Ariyan S, Camp RL, Rimm DL, Mor G. The X-linked inhibitor of apoptosis protein (XIAP) is up-regulated in metastatic melanoma, and XIAP cleavage by Phenoxodiol is associated with Carboplatin sensitization. Journal Of Translational Medicine 2007, 5: 6. PMID: 17257402, PMCID: PMC1796544, DOI: 10.1186/1479-5876-5-6.Peer-Reviewed Original ResearchConceptsMetastatic melanomaXIAP expressionCell linesCy5-conjugated antibodiesMechanism of actionMelanoma cell linesPrimary lesionOvarian cancerTherapeutic approachesTissue microarrayDisease aggressionCarboplatin sensitivityChemotherapy resistanceMalignant progressionClinical specimensBenign counterpartsCarboplatinMelanomaChemotherapy sensitizationPrimary specimensPhenoxodiolResistant cellsMelanoma cellsHigh expressionMelanoma resistance
2006
What's in a name?
Rimm DL. What's in a name? Archives Of Pathology & Laboratory Medicine 2006, 130: 934-5. PMID: 16831045, DOI: 10.5858/2006-130-934-wian.Peer-Reviewed Original ResearchExpression of Tumor Necrosis Factor–Related Apoptosis-Inducing Ligand Receptors 1 and 2 in Melanoma
McCarthy MM, DiVito KA, Sznol M, Kovacs D, Halaban R, Berger AJ, Flaherty KT, Camp RL, Lazova R, Rimm DL, Kluger HM. Expression of Tumor Necrosis Factor–Related Apoptosis-Inducing Ligand Receptors 1 and 2 in Melanoma. Clinical Cancer Research 2006, 12: 3856-3863. PMID: 16778114, PMCID: PMC1839847, DOI: 10.1158/1078-0432.ccr-06-0190.Peer-Reviewed Original Research
2005
Using 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 tissuesUpstaging based solely on positive peritoneal washing does not affect outcome in endometrial cancer
Fadare O, Mariappan MR, Hileeto D, Wang, Mcalpine JN, Rimm DL. Upstaging based solely on positive peritoneal washing does not affect outcome in endometrial cancer. Modern Pathology 2005, 18: 673-680. PMID: 15578078, DOI: 10.1038/modpathol.3800342.Peer-Reviewed Original ResearchConceptsEndometrial carcinomaControl groupEndometrial cancerPeritoneal washingsPrognostic significanceStage IAge-matched control groupPositive peritoneal washingsSame histologic subtypeEndometrial carcinoma patientsPeritoneal washing cytologyProgression of diseaseExtra-uterine tumoursSingle-site studyExtrauterine diseasePositive washingsAbnormal cytologyAdjuvant therapySurgical stagingPositive cytologyCarcinoma patientsHistologic subtypeWashing cytologyHistologic evidenceIntraperitoneal disease
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
1998
Loss of p120ctn in human colorectal cancer predicts metastasis and poor survival
Gold J, Reynolds A, Rimm D. Loss of p120ctn in human colorectal cancer predicts metastasis and poor survival. Cancer Letters 1998, 132: 193-201. PMID: 10397474, DOI: 10.1016/s0304-3835(98)00190-6.Peer-Reviewed Original ResearchConceptsColorectal cancerPrimary human colorectal adenocarcinomasHigher stage diseasePoor clinical outcomeHuman colorectal cancerHuman colorectal adenocarcinomaStage diseaseClinical outcomesNodal metastasisColorectal adenocarcinomaPoor survivalColorectal tumorsColon cancerImmunohistochemical methodsMetastasisReduced expressionCancerE-cadherinP120ctn expressionLoss of p120ctnFamily membersSurvivalPreliminary studyExpressionComplete loss