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
Spatially Resolved and Quantitative Analysis of VISTA/PD-1H as a Novel Immunotherapy Target in Human Non–Small Cell Lung Cancer
Villarroel-Espindola F, Yu X, Datar I, Mani N, Sanmamed M, Velcheti V, Syrigos K, Toki M, Zhao H, Chen L, Herbst RS, Schalper KA. Spatially Resolved and Quantitative Analysis of VISTA/PD-1H as a Novel Immunotherapy Target in Human Non–Small Cell Lung Cancer. Clinical Cancer Research 2018, 24: 1562-1573. PMID: 29203588, PMCID: PMC5884702, DOI: 10.1158/1078-0432.ccr-17-2542.Peer-Reviewed Original ResearchMeSH KeywordsAgedAntigens, CDAntigens, Differentiation, MyelomonocyticB7 AntigensB7-H1 AntigenBiomarkers, TumorCarcinoma, Non-Small-Cell LungCD8-Positive T-LymphocytesEvaluation Studies as TopicFemaleGene Expression Regulation, NeoplasticHumansImmunologic FactorsImmunotherapyLung NeoplasmsMaleMembrane ProteinsMutationProgrammed Cell Death 1 ReceptorRetrospective StudiesConceptsNon-small cell lung cancerHuman non-small cell lung cancerT helper cellsCytotoxic T cellsT cellsPD-1Localized expression patternQuantitative immunofluorescenceTumor-infiltrating lymphocytesCell lung cancerLung cancer casesGenomic analysisTissue microarray formatTumor-associated macrophagesPD-L1 proteinCytoplasmic staining patternClin Cancer ResExpression patternsLow mutational burdenTumor epithelial cellsSpecific genomic alterationsVISTA expressionVISTA proteinPD-L1Immunomodulatory roleClinical 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 riskB7-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 stage
2016
Quantitative and pathologist-read comparison of the heterogeneity of programmed death-ligand 1 (PD-L1) expression in non-small cell lung cancer
Rehman JA, Han G, Carvajal-Hausdorf DE, Wasserman BE, Pelekanou V, Mani NL, McLaughlin J, Schalper KA, Rimm DL. Quantitative and pathologist-read comparison of the heterogeneity of programmed death-ligand 1 (PD-L1) expression in non-small cell lung cancer. Modern Pathology 2016, 30: 340-349. PMID: 27834350, PMCID: PMC5334264, DOI: 10.1038/modpathol.2016.186.Peer-Reviewed Original ResearchConceptsPD-L1 expressionPD-L1Immune cellsImmune cell PD-L1 expressionNon-small cell lung cancerNon-small cell lung cancer (NSCLC) casesCell lung cancer casesTumor cellsPD-L1 assessmentStromal immune cellsPD-L1 positivityCell lung cancerLung cancer patientsLung cancer casesRepresentative tumor areasPathologist scoresLikelihood of responseConcordance correlation coefficientRabbit monoclonal antibodyIntraclass correlation coefficientCancer patientsLung cancerImmunohistochemistry slidesCancer casesTumor tissueEGFR-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 markerQuantitative 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
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 ileumSpironolactone inhibits the activity of the Na+/H+ exchanger in the aorta of mineralocorticoid-induced hypertensive rats
Carreño JE, Verdugo FJ, Contreras F, Montellano FA, Veloso S, Schalper KA, Sandoval M, Villanueva S, Marusic E, Irarrazabal CE. Spironolactone inhibits the activity of the Na+/H+ exchanger in the aorta of mineralocorticoid-induced hypertensive rats. Journal Of The Renin-Angiotensin-Aldosterone System 2015, 16: 1225-1231. PMID: 25997821, DOI: 10.1177/1470320315587193.Peer-Reviewed Original ResearchConceptsNHE-1 activityMineralocorticoid receptor activationEthyl isopropyl amilorideVascular contractilityHypertensive ratsReceptor activationMale Sprague-Dawley ratsUninephrectomized male Sprague-Dawley ratsChronic DOCA treatmentDiastolic blood pressureAortic wall thicknessWeeks of treatmentVascular smooth muscle cellsProtein levelsSprague-Dawley ratsSmooth muscle cellsNHE-1 mRNADOCA treatmentBlood pressureDOCA administrationExchanger isoform 1Rat aortaDOCA groupSpironolactoneAorta
2014
Quantitative measurement of cancer tissue biomarkers in the lab and in the clinic
Carvajal-Hausdorf D, Schalper KA, Neumeister V, Rimm DL. Quantitative measurement of cancer tissue biomarkers in the lab and in the clinic. Laboratory Investigation 2014, 95: 385-396. PMID: 25502176, PMCID: PMC4383674, DOI: 10.1038/labinvest.2014.157.Peer-Reviewed Original ResearchMutacin 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
Programmed death ligand-1 expression in non-small cell lung cancer
Velcheti V, Schalper KA, Carvajal DE, Anagnostou VK, Syrigos KN, Sznol M, Herbst RS, Gettinger SN, Chen L, Rimm DL. Programmed death ligand-1 expression in non-small cell lung cancer. Laboratory Investigation 2013, 94: 107-116. PMID: 24217091, PMCID: PMC6125250, DOI: 10.1038/labinvest.2013.130.Peer-Reviewed Original ResearchMeSH KeywordsAgedB7-H1 AntigenBiomarkers, TumorCarcinoma, Non-Small-Cell LungCell Line, TumorChi-Square DistributionCohort StudiesConnecticutFemaleGreeceHumansImmunohistochemistryLung NeoplasmsLymphocytes, Tumor-InfiltratingMalePrognosisReproducibility of ResultsRNA, MessengerSurvival AnalysisTissue Array AnalysisConceptsNon-small cell lung cancerPD-L1 expressionCell lung cancerPD-L1Tissue microarrayBetter outcomesNSCLC casesLung cancerDeath ligand 1 (PD-L1) expressionCell death ligand 1PD-L1 protein expressionEarly phase clinical trialsLigand 1 expressionTumor-infiltrating lymphocytesDeath ligand 1Significant better outcomePD-L1 mRNAPD-L1 proteinPhase clinical trialsNormal human placentaPrediction of responseQuantitative fluorescence approachesFrequency of expressionPD-1Prognostic valueExpresin 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 ResearchMutacin 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
2012
p16ink4a Expression in Benign and Malignant Melanocytic Conjunctival Lesions
Zoroquiain P, Fernandes BF, González S, Novais GN, Schalper KA, Burnier MN. p16ink4a Expression in Benign and Malignant Melanocytic Conjunctival Lesions. International Journal Of Surgical Pathology 2012, 20: 240-245. PMID: 22287653, DOI: 10.1177/1066896911435697.Peer-Reviewed Original ResearchConceptsConjunctival melanocytic lesionsImmunoreactive scoreMelanocytic lesionsGerman immunoreactive scoreMean immunoreactive scoreRoutine microscopic analysisMalignant melanocytic lesionsConjunctival melanomaConjunctival lesionsImmunohistochemical expressionImmunohistochemical studyMortality rateHigh metastasisLarge seriesMalignant melanocytic neoplasmsLesionsP16 expressionMelanomaGood markerNeviAdditional studiesMelanocytic neoplasmsAtypiaUnfavorable locationP16
2011
Primary cerebral lymphomatoid granulomatosis in a HIV-positive patient. Case report.
Schalper K, Valbuena J. Primary cerebral lymphomatoid granulomatosis in a HIV-positive patient. Case report. Revista Medica De Chile 2011, 139: 218-23. PMID: 21773660, DOI: /s0034-98872011000200012.Peer-Reviewed Original ResearchConceptsLymphomatoid granulomatosisHuman immunodeficiency virus (HIV) infectionHIV-positive patientsImmunodeficiency virus infectionEBV-positive cellsSubcortical nodulesCerebral biopsyChest painHepatitis BLymphoid infiltratesReactive gliosisVirus infectionImaging studiesWeight lossGranulomatosisPatientsGliosisInfiltratesPainCD20BiopsyHospitalInfection