2024
High-throughput transcriptome profiling indicates ribosomal RNAs to be associated with resistance to immunotherapy in non-small cell lung cancer (NSCLC)
Moutafi M, Bates K, Aung T, Milian R, Xirou V, Vathiotis I, Gavrielatou N, Angelakis A, Schalper K, Salichos L, Rimm D. High-throughput transcriptome profiling indicates ribosomal RNAs to be associated with resistance to immunotherapy in non-small cell lung cancer (NSCLC). Journal For ImmunoTherapy Of Cancer 2024, 12: e009039. PMID: 38857914, PMCID: PMC11168162, DOI: 10.1136/jitc-2024-009039.Peer-Reviewed Original ResearchConceptsNon-small cell lung cancerImmune checkpoint inhibitorsProgrammed cell death protein 1Associated with OSCell lung cancerTissue microarray spotsTissue microarrayValidation cohortLung cancerNon-small cell lung cancer treated with immune checkpoint inhibitorsAssociated with resistance to immunotherapyCell death protein 1Resistance to immunotherapyAssociated with PFSProgression-free survivalSecreted frizzled-related protein 2Cox proportional-hazards model analysisCheckpoint inhibitorsImmunotherapy strategiesTumor compartmentsRetrospective cohortDiscovery cohortLong-term benefitsPatientsCD68
2018
Clinical Features and Management of Acquired Resistance to PD-1 Axis Inhibitors in 26 Patients With Advanced Non–Small Cell Lung Cancer
Gettinger SN, Wurtz A, Goldberg SB, Rimm D, Schalper K, Kaech S, Kavathas P, Chiang A, Lilenbaum R, Zelterman D, Politi K, Herbst R. Clinical Features and Management of Acquired Resistance to PD-1 Axis Inhibitors in 26 Patients With Advanced Non–Small Cell Lung Cancer. Journal Of Thoracic Oncology 2018, 13: 831-839. PMID: 29578107, PMCID: PMC6485248, DOI: 10.1016/j.jtho.2018.03.008.Peer-Reviewed Original ResearchConceptsPD-1 axis inhibitorsNon-small cell lung cancerAdvanced non-small cell lung cancerCell lung cancerInhibitor therapyLocal therapyLymph nodesLung cancerSurvival rateSolid Tumors v1.1Response Evaluation CriteriaSite of diseaseProgression of diseaseProgressive diseaseClinical patternLN metastasisSuch patientsClinical featuresMedian timeRadiographic featuresTumor regressionProlonged benefitPatientsTherapyResponse criteria
2017
Prediction of recurrence in early stage non-small cell lung cancer using computer extracted nuclear features from digital H&E images
Wang X, Janowczyk A, Zhou Y, Thawani R, Fu P, Schalper K, Velcheti V, Madabhushi A. Prediction of recurrence in early stage non-small cell lung cancer using computer extracted nuclear features from digital H&E images. Scientific Reports 2017, 7: 13543. PMID: 29051570, PMCID: PMC5648794, DOI: 10.1038/s41598-017-13773-7.Peer-Reviewed Original ResearchMeSH KeywordsAgedArea Under CurveCarcinoma, Non-Small-Cell LungCell NucleusCohort StudiesDiscriminant AnalysisFemaleHumansKaplan-Meier EstimateLung NeoplasmsMaleMiddle AgedNeoplasm Recurrence, LocalNeoplasm StagingPrognosisProportional Hazards ModelsRetrospective StudiesROC CurveTissue Array AnalysisConceptsNon-small cell lung cancerEarly-stage non-small cell lung cancerStage non-small cell lung cancerEarly-stage NSCLC patientsStage NSCLC patientsCell lung cancerPrediction of recurrenceDisease recurrenceNSCLC patientsLung cancerTissue microarrayMultivariable Cox proportional hazards modelsCox proportional hazards modelTraditional prognostic variablesIndependent prognostic factorIdentification of patientsProportional hazards modelAdjuvant therapyNodal statusPrognostic factorsRetrospective cohortValidation cohortTraining cohortPrognostic variablesHigh riskObjective measurement and clinical significance of IDO1 protein in hormone receptor-positive breast cancer
Carvajal-Hausdorf DE, Mani N, Velcheti V, Schalper KA, Rimm DL. Objective measurement and clinical significance of IDO1 protein in hormone receptor-positive breast cancer. Journal For ImmunoTherapy Of Cancer 2017, 5: 81. PMID: 29037255, PMCID: PMC5644103, DOI: 10.1186/s40425-017-0285-7.Peer-Reviewed Original ResearchConceptsHormone receptor-positive breast cancerReceptor-positive breast cancerIDO1 expressionBreast cancerIndependent negative prognostic markerB cell infiltrationImmune suppressive pathwaysAdvanced solid tumorsTumor-infiltrating lymphocytesT cell responsesClinico-pathological featuresClinico-pathological characteristicsProportional hazards modelNegative prognostic markerDegradation of tryptophanMann-Whitney testFoxp3 levelsIDO1 blockadeIDO1 levelsEffector CD4Durable responsesOverall survivalImmune toleranceMultivariable analysisPrognostic markerB7-H3 Expression in NSCLC and Its Association with B7-H4, PD-L1 and Tumor-Infiltrating Lymphocytes
Altan M, Pelekanou V, Schalper KA, Toki M, Gaule P, Syrigos K, Herbst RS, Rimm DL. B7-H3 Expression in NSCLC and Its Association with B7-H4, PD-L1 and Tumor-Infiltrating Lymphocytes. Clinical Cancer Research 2017, 23: 5202-5209. PMID: 28539467, PMCID: PMC5581684, DOI: 10.1158/1078-0432.ccr-16-3107.Peer-Reviewed Original ResearchMeSH KeywordsAdultAgedB7 AntigensB7-H1 AntigenBiomarkers, TumorCarcinoma, Non-Small-Cell LungCell Line, TumorDisease-Free SurvivalFemaleGene Expression Regulation, NeoplasticHumansImmunohistochemistryLymphocytes, Tumor-InfiltratingMaleMiddle AgedPrognosisV-Set Domain-Containing T-Cell Activation Inhibitor 1ConceptsNon-small cell lung cancerTumor-infiltrating lymphocytesB7-H3 proteinB7-H4PD-L1B7-H3Majority of NSCLCQuantitative immunofluorescenceImmune checkpoints PD-1Major clinicopathologic variablesLevels of CD3Negative prognostic impactCell lung cancerPoor overall survivalSuccessful therapeutic targetsB7 family membersClin Cancer ResB7-H1NSCLC cohortOverall survivalPrognostic impactSmoking historyClinicopathologic characteristicsPD-1Clinical stageObjective, domain-specific HER2 measurement in uterine and ovarian serous carcinomas and its clinical significance
Carvajal-Hausdorf DE, Schalper KA, Bai Y, Black J, Santin AD, Rimm DL. Objective, domain-specific HER2 measurement in uterine and ovarian serous carcinomas and its clinical significance. Gynecologic Oncology 2017, 145: 154-158. PMID: 28196634, PMCID: PMC5941302, DOI: 10.1016/j.ygyno.2017.02.002.Peer-Reviewed Original ResearchMeSH KeywordsAdo-Trastuzumab EmtansineAfatinibAntibodies, Monoclonal, HumanizedAntineoplastic AgentsCohort StudiesExtracellular SpaceFemaleFluorescent Antibody TechniqueHumansIntracellular SpaceLapatinibMaytansineMiddle AgedNeoplasms, Cystic, Mucinous, and SerousOvarian NeoplasmsProtein DomainsQuinazolinesReceptor, ErbB-2Retrospective StudiesTissue Array AnalysisTrastuzumabUterine NeoplasmsConceptsUterine serous carcinomaOvarian serous carcinomaHER2 intracellular domainSerous carcinomaECD levelsECD statusTissue microarrayHER2 measurementQuantitative immunofluorescenceHER2 overexpression/amplificationClinico-pathologic characteristicsClinico-pathological featuresHER2-targeted agentsIntracellular domainOverexpression/amplificationHER2 extracellular domainExtracellular domainOSC patientsClinical trialsBreast cancerClinical significancePatientsHER2 assaysP95-HER2CarcinomaDifferential Expression and Significance of PD-L1, IDO-1, and B7-H4 in Human Lung Cancer
Schalper KA, Carvajal-Hausdorf D, McLaughlin J, Altan M, Velcheti V, Gaule P, Sanmamed MF, Chen L, Herbst RS, Rimm DL. Differential Expression and Significance of PD-L1, IDO-1, and B7-H4 in Human Lung Cancer. Clinical Cancer Research 2017, 23: 370-378. PMID: 27440266, PMCID: PMC6350535, DOI: 10.1158/1078-0432.ccr-16-0150.Peer-Reviewed Original ResearchMeSH KeywordsA549 CellsAgedB7-H1 AntigenBiomarkers, TumorCarcinoma, Non-Small-Cell LungDisease-Free SurvivalDrug Resistance, NeoplasmGene Expression Regulation, NeoplasticHumansIndoleamine-Pyrrole 2,3,-DioxygenaseInterferon-gammaInterleukin-10Lymphocytes, Tumor-InfiltratingMiddle AgedNeoplasm StagingRNA, MessengerV-Set Domain-Containing T-Cell Activation Inhibitor 1ConceptsNon-small cell lung cancerB7-H4PD-L1IDO-1Lung cancerLung carcinomaQuantitative immunofluorescenceIFNγ stimulationElevated PD-L1Major clinicopathologic variablesMultiplexed quantitative immunofluorescenceOptimal clinical trialsT-cell infiltratesCell lung cancerImmune evasion pathwaysHuman lung carcinomaLung adenocarcinoma A549Cancer Genome AtlasClinicopathologic variablesMarker levelsClinical trialsStage ITherapeutic resistanceTCGA datasetA549 cells
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 tumorsEGFR-GRB2 Protein Colocalization Is a Prognostic Factor Unrelated to Overall EGFR Expression or EGFR Mutation in Lung Adenocarcinoma
Toki MI, Carvajal-Hausdorf DE, Altan M, McLaughlin J, Henick B, Schalper KA, Syrigos KN, Rimm DL. EGFR-GRB2 Protein Colocalization Is a Prognostic Factor Unrelated to Overall EGFR Expression or EGFR Mutation in Lung Adenocarcinoma. Journal Of Thoracic Oncology 2016, 11: 1901-1911. PMID: 27449805, PMCID: PMC5075503, DOI: 10.1016/j.jtho.2016.06.025.Peer-Reviewed Original ResearchConceptsEGFR pathway activationSeries of patientsLung adenocarcinomaMutation statusEGFR expressionPathway activationProximity ligation assayKRAS wild-type tumorsEGFR-mutant patientsKRAS-mutant casesCohort of patientsWild-type tumorsInteraction of EGFREGFR expression levelsEGFR protein expressionMAPK/ERK pathwayGrowth factor receptorActive EGFRPrognostic factorsDifferent mutation statusPatient groupPrognostic valueLonger survivalEGFR mutationsPrognostic marker
2015
Effect of cholecystectomy on bile acid synthesis and circulating levels of fibroblast growth factor 19
Barrera F, Azocar L, Molina H, Schalper KA, Ocares M, Liberona J, Villarroel L, Pimentel F, Pérez-Ayuso RM, Nervi F, Groen AK, Miquel JF. Effect of cholecystectomy on bile acid synthesis and circulating levels of fibroblast growth factor 19. Annals Of Hepatology 2015, 14: 710-721. PMID: 26256900, DOI: 10.1016/s1665-2681(19)30766-5.Peer-Reviewed Original ResearchConceptsEffect of cholecystectomyBile acid synthesisBA synthesisFGF19 expressionFibroblast growth factor 19FGF19 mRNA levelsGallstone disease patientsGut-derived hormonesGrowth factor 19GB-d1 cellsDose-dependent expressionGallbladder refillingFGF19 levelsBA metabolismSerum levelsSerum cholesterolDisease patientsSerum changesSerum FGF19Metabolic dysregulationTerminal ileumCholecystectomyFGF19 mRNAFactor 19Distal ileumMeasurement of Domain-Specific HER2 (ERBB2) Expression May Classify Benefit From Trastuzumab in Breast Cancer
Carvajal-Hausdorf DE, Schalper KA, Pusztai L, Psyrri A, Kalogeras KT, Kotoula V, Fountzilas G, Rimm DL. Measurement of Domain-Specific HER2 (ERBB2) Expression May Classify Benefit From Trastuzumab in Breast Cancer. Journal Of The National Cancer Institute 2015, 107: djv136. PMID: 25991002, PMCID: PMC4554192, DOI: 10.1093/jnci/djv136.Peer-Reviewed Original ResearchMeSH KeywordsAdultAgedAntibodies, Monoclonal, HumanizedAntineoplastic AgentsAntineoplastic Combined Chemotherapy ProtocolsBiomarkers, TumorBreast NeoplasmsChemotherapy, AdjuvantClinical Trials as TopicDisease-Free SurvivalExtracellular SpaceFemaleFluorescent Antibody TechniqueGene Expression Regulation, NeoplasticHumansIntracellular SpaceKaplan-Meier EstimateMiddle AgedPredictive Value of TestsPrognosisReceptor, ErbB-2Sensitivity and SpecificityTissue Array AnalysisTrastuzumabTreatment OutcomeConceptsHuman epidermal growth factor receptor 2ECD expressionICD statusLonger DFSQuantitative immunofluorescenceTrastuzumab therapyPrognostic valueBreast cancerTissue microarrayEpidermal growth factor receptor 2Adjuvant trastuzumab therapyDisease-free survival analysisTrastuzumab-treated patientsGrowth factor receptor 2High positive predictive valueHER2-positive tumorsKaplan-Meier estimatesFactor receptor 2ERBB2 gene amplificationHER2 protein expressionPositive predictive valueExtracellular domainAdjuvant chemotherapyHER2-ICDBetter DFSPD-L1 Expression Correlates with Tumor-Infiltrating Lymphocytes and Response to Neoadjuvant Chemotherapy in Breast Cancer
Wimberly H, Brown JR, Schalper K, Haack H, Silver MR, Nixon C, Bossuyt V, Pusztai L, Lannin DR, Rimm DL. PD-L1 Expression Correlates with Tumor-Infiltrating Lymphocytes and Response to Neoadjuvant Chemotherapy in Breast Cancer. Cancer Immunology Research 2015, 3: 326-332. PMID: 25527356, PMCID: PMC4390454, DOI: 10.1158/2326-6066.cir-14-0133.Peer-Reviewed Original ResearchConceptsTumor-infiltrating lymphocytesPD-L1 expressionPathologic complete responseNeoadjuvant chemotherapyPD-L1Breast cancerDeath 1 ligand 1PD-L1 protein expressionYale-New Haven HospitalHigh PD-L1Antitumor immune activitySubset of patientsTriple-negative patientsBreast cancer patientsTriple-negative statusImmune checkpoint proteinsImmune regulatory moleculesNew Haven HospitalSignificant multivariate modelRabbit monoclonal antibodyTILs correlateComplete responseImmune therapyCancer patientsImmune activity
2014
In Situ Tumor PD-L1 mRNA Expression Is Associated with Increased TILs and Better Outcome in Breast Carcinomas
Schalper KA, Velcheti V, Carvajal D, Wimberly H, Brown J, Pusztai L, Rimm DL. In Situ Tumor PD-L1 mRNA Expression Is Associated with Increased TILs and Better Outcome in Breast Carcinomas. Clinical Cancer Research 2014, 20: 2773-2782. PMID: 24647569, DOI: 10.1158/1078-0432.ccr-13-2702.Peer-Reviewed Original ResearchB7-H1 AntigenBreast NeoplasmsCell Line, TumorFemaleFluorescent Antibody TechniqueGene Expression Regulation, NeoplasticHumansIn Situ HybridizationKaplan-Meier EstimateLymphatic MetastasisLymphocytes, Tumor-InfiltratingMiddle AgedMultivariate AnalysisNeoplasm Recurrence, LocalPrognosisReceptor, ErbB-2Receptors, EstrogenRNA, MessengerTissue Array AnalysisMutacin del gen BRAF en pacientes con cnceres de colon y recto con KRAS no mutado
Roa I, Game A, Bizama C, Schalper K. Mutacin del gen BRAF en pacientes con cnceres de colon y recto con KRAS no mutado. Revista Medica De Chile 2014, 142: 55-60. PMID: 24861115, DOI: 10.4067/s0034-98872014000100009.Peer-Reviewed Original ResearchConceptsBRAF V600E mutationV600E mutationColorectal cancerPrimary tumorKRAS mutationsIndependent prognostic factorBRAF gene mutationRestriction fragment length polymorphismColorectal cancer samplesGrowth factor pathwaysLiver metastasesPrognostic factorsMetastatic adenocarcinomaTumor locationBRAF geneFactor pathwayMonoclonal antibodiesCancer samplesMutation casesGene mutationsTissue samplesPatientsDirect sequencingMetastasisColon
2013
Expresin y amplificacin del gen HER2 en el cncer gstrico avanzado
Roa I, Slater J, Carvajal D, Schalper K, de Toro G, Ares R, Game A, Len J, de Aretxabala X. Expresin y amplificacin del gen HER2 en el cncer gstrico avanzado. Revista Medica De Chile 2013, 141: 1411-1419. PMID: 24718467, DOI: 10.4067/s0034-98872013001100007.Peer-Reviewed Original ResearchA Retrospective Population-Based Comparison of HER2 Immunohistochemistry and Fluorescence In Situ Hybridization in Breast Carcinomas: Impact of 2007 American Society of Clinical Oncology/ College of American Pathologists Criteria
Schalper KA, Kumar S, Hui P, Rimm DL, Gershkovich P. A Retrospective Population-Based Comparison of HER2 Immunohistochemistry and Fluorescence In Situ Hybridization in Breast Carcinomas: Impact of 2007 American Society of Clinical Oncology/ College of American Pathologists Criteria. Archives Of Pathology & Laboratory Medicine 2013, 138: 213-9. PMID: 24164555, DOI: 10.5858/arpa.2012-0617-oa.Peer-Reviewed Original ResearchMeSH KeywordsAdultAgedAged, 80 and overBreast NeoplasmsCarcinomaCohort StudiesConnecticutFemaleHospitals, UniversityHumansImmunohistochemistryIn Situ Hybridization, FluorescenceMammary Glands, HumanMiddle AgedNeoplasm GradingNeoplasm InvasivenessNeoplasm ProteinsPractice Guidelines as TopicReceptor, ErbB-2Retrospective StudiesSocieties, MedicalUnited StatesUnited States Food and Drug AdministrationMutacin del gen KRAS en el cncer de colon y recto
Roa I, Snchez T, Majlis A, Schalper K. Mutacin del gen KRAS en el cncer de colon y recto. Revista Medica De Chile 2013, 141: 1166-1172. PMID: 24522420, DOI: 10.4067/s0034-98872013000900009.Peer-Reviewed Original ResearchConceptsKRAS mutationsPrimary tumorColorectal cancer tissue samplesTissue samplesColo-rectal cancerCancer tissue samplesColorectal cancerMetastatic tumorsTumor locationColorectal carcinogenesisG12C mutationCodon 13KRAS oncogeneCodon 12Tumor samplesTumorsExtraction sitesDirect sequencingCancerDistribution of mutationsMutationsPoint mutationsMetastasisRectumColonMarginal 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 differencesSarcomatoid Lung Carcinomas Show High Levels of Programmed Death Ligand-1 (PD-L1)
Velcheti V, Rimm DL, Schalper KA. Sarcomatoid Lung Carcinomas Show High Levels of Programmed Death Ligand-1 (PD-L1). Journal Of Thoracic Oncology 2013, 8: 803-805. PMID: 23676558, PMCID: PMC3703468, DOI: 10.1097/jto.0b013e318292be18.Peer-Reviewed Original ResearchConceptsDeath ligand 1Sarcomatoid carcinomaCell lung carcinomaLung carcinomaPD-L1PD-1/PD-L1 axisPD-1/PD-L1 pathwayProgrammed Death Ligand 1PD-L1 protein expressionEffector immune responsesPD-L1 axisPD-L1 pathwayLung sarcomatoid carcinomaLung cancer cohortSarcomatoid lung carcinomasLigand 1Mouse monoclonal antibodyDeath-1Lymphocytic infiltrationRare subtypeSuch therapyCancer cohortT cellsCarcinomaTumor typesHigh SOX2 Levels Predict Better Outcome in Non-Small Cell Lung Carcinomas
Velcheti V, Schalper K, Yao X, Cheng H, Kocoglu M, Dhodapkar K, Deng Y, Gettinger S, Rimm DL. High SOX2 Levels Predict Better Outcome in Non-Small Cell Lung Carcinomas. PLOS ONE 2013, 8: e61427. PMID: 23620753, PMCID: PMC3631238, DOI: 10.1371/journal.pone.0061427.Peer-Reviewed Original ResearchConceptsSquamous cell carcinomaLonger survivalTissue microarrayMultivariate analysisIndependent lung cancer cohortsIndependent positive prognostic markerSOX2 levelsNon-small cell lung carcinomaQuantitative immunofluorescenceLung squamous cell carcinomaSecond independent validation cohortSOX2 expressionHigh SOX2 levelsLog rank pSOX2 overexpressionPositive prognostic markerRisk of deathClinico-pathological characteristicsClinico-pathological variablesCox univariate analysisIndependent validation cohortCell lung carcinomaLung cancer cohortNSCLC patientsOverall survival