2023
Emerging Prognostic and Predictive Significance of Stress Keratin 17 in HPV-Associated and Non HPV-Associated Human Cancers: A Scoping Review
Lozar T, Wang W, Gavrielatou N, Christensen L, Lambert P, Harari P, Rimm D, Burtness B, Kuhar C, Carchman E. Emerging Prognostic and Predictive Significance of Stress Keratin 17 in HPV-Associated and Non HPV-Associated Human Cancers: A Scoping Review. Viruses 2023, 15: 2320. PMID: 38140561, PMCID: PMC10748233, DOI: 10.3390/v15122320.Peer-Reviewed Original ResearchConceptsSquamous cell carcinomaTriple-negative breast cancerCancer typesPredictive significancePrognostic factorsClinical outcomesPrognostic significanceCell carcinomaHuman cancersCervical squamous cell carcinomaNeck squamous cell carcinomaAvailable clinical evidenceCochrane Central RegisterInferior clinical outcomesPositive prognostic factorNegative predictive factorNegative prognostic factorWeb of ScienceCentral RegisterControlled TrialsCervical cancerClinical evidencePredictive factorsPancreatic cancerEligible studiesDeep computational image analysis of immune cell niches reveals treatment-specific outcome associations in lung cancer
Barrera C, Corredor G, Viswanathan V, Ding R, Toro P, Fu P, Buzzy C, Lu C, Velu P, Zens P, Berezowska S, Belete M, Balli D, Chang H, Baxi V, Syrigos K, Rimm D, Velcheti V, Schalper K, Romero E, Madabhushi A. Deep computational image analysis of immune cell niches reveals treatment-specific outcome associations in lung cancer. Npj Precision Oncology 2023, 7: 52. PMID: 37264091, PMCID: PMC10235089, DOI: 10.1038/s41698-023-00403-x.Peer-Reviewed Original ResearchNon-small cell lung cancerTumor-infiltrating lymphocytesLung cancerEffective adaptive immune responseImmune checkpoint blockersCell lung cancerLung cancer patientsTumor immune microenvironmentAdaptive immune responsesImmune-related biomarkersTreatment-specific outcomesCheckMate 057Histology variantsImmunotherapy resistanceCheckpoint blockersRegulatory cellsTumor rejectionTumor-immune interactionsClinical outcomesImmunosuppressive signalsClinical benefitInfluence prognosisImmune microenvironmentCancer patientsPatient outcomes
2021
What if the future of HER2‐positive breast cancer patients was written in miRNAs? An exploratory analysis from NeoALTTO study
Pizzamiglio S, Cosentino G, Ciniselli CM, De Cecco L, Cataldo A, Plantamura I, Triulzi T, El‐abed S, Wang Y, Bajji M, Nuciforo P, Huober J, Ellard SL, Rimm DL, Gombos A, Daidone MG, Verderio P, Tagliabue E, Di Cosimo S, Iorio MV. What if the future of HER2‐positive breast cancer patients was written in miRNAs? An exploratory analysis from NeoALTTO study. Cancer Medicine 2021, 11: 332-339. PMID: 34921525, PMCID: PMC8729061, DOI: 10.1002/cam4.4449.Peer-Reviewed Original ResearchConceptsHER2-positive breast cancer patientsEvent-free survivalBreast cancer patientsNeoadjuvant therapyCancer patientsPathological complete response rateSingle-agent trastuzumabTwo-miRNA signatureComplete response rateDifferential clinical outcomesPredictive miRNA signatureTrastuzumab armBaseline biopsiesClinical outcomesPathological variablesPrognostic valueUnivariate analysisAgent trastuzumabPrognostic signatureResponse ratePatientsTissue miRNAsMiRNA expression profilesMiRNA signatureMultivariate modelDeep learning trained on hematoxylin and eosin tumor region of Interest predicts HER2 status and trastuzumab treatment response in HER2+ breast cancer
Farahmand S, Fernandez AI, Ahmed FS, Rimm DL, Chuang JH, Reisenbichler E, Zarringhalam K. Deep learning trained on hematoxylin and eosin tumor region of Interest predicts HER2 status and trastuzumab treatment response in HER2+ breast cancer. Modern Pathology 2021, 35: 44-51. PMID: 34493825, PMCID: PMC10221954, DOI: 10.1038/s41379-021-00911-w.Peer-Reviewed Original ResearchConceptsHER2 statusBreast cancerTreatment responseHER2-positive breast cancerAnti-HER2 agentsPre-treatment samplesNeoadjuvant chemotherapyTrastuzumab therapyClinical outcomesClinical evaluationProtein immunohistochemistryHER2 amplificationTrastuzumab responseTumor stainTreatment selectionTCGA testPathology teamTumor regionCancer featuresCancerPatientsHER2Current standardImmunohistochemistryHematoxylinPD-L1 as a biomarker of response to immune-checkpoint inhibitors
Doroshow DB, Bhalla S, Beasley MB, Sholl LM, Kerr KM, Gnjatic S, Wistuba II, Rimm DL, Tsao MS, Hirsch FR. PD-L1 as a biomarker of response to immune-checkpoint inhibitors. Nature Reviews Clinical Oncology 2021, 18: 345-362. PMID: 33580222, DOI: 10.1038/s41571-021-00473-5.Peer-Reviewed Original ResearchConceptsImmune checkpoint inhibitorsSelection of patientsPD-L1L1 antibodyImmunohistochemistry assaysPD-L1 immunohistochemistry assaysOutcomes of patientsBiomarkers of responseCompanion diagnostic assayTypes of cancerPD-1Clinical outcomesSelection biomarkerProspective comparisonClinical challengeNew therapiesFuture treatmentPatientsSolid tumorsClinical useSpecific agentsInter-assay variabilityBiomarkersCurrent roleDiagnostic assays
2020
Biomarkers Associated with Beneficial PD-1 Checkpoint Blockade in Non–Small Cell Lung Cancer (NSCLC) Identified Using High-Plex Digital Spatial Profiling
Zugazagoitia J, Gupta S, Liu Y, Fuhrman K, Gettinger S, Herbst RS, Schalper KA, Rimm DL. Biomarkers Associated with Beneficial PD-1 Checkpoint Blockade in Non–Small Cell Lung Cancer (NSCLC) Identified Using High-Plex Digital Spatial Profiling. Clinical Cancer Research 2020, 26: 4360-4368. PMID: 32253229, PMCID: PMC7442721, DOI: 10.1158/1078-0432.ccr-20-0175.Peer-Reviewed Original ResearchConceptsNon-small cell lung cancerPD-1 checkpoint blockadeCell lung cancerCheckpoint blockadeLung cancerAdvanced non-small cell lung cancerUnivariate unadjusted analysisProgression-free survivalImmune cell countsMinority of patientsRobust predictive biomarkersBiomarkers of responseLarge independent cohortsSpatial profiling technologyDigital spatial profilingDigital spatial profiling (DSP) technologyOverall survivalClinical outcomesImmune predictorsHigher CD56NSCLC casesPredictive biomarkersUnadjusted analysesImmune parametersTissue microarray
2019
Quantitative 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 recommendationsPatientsQuantitative assessment of immune cell populations and associations with clinical outcomes in African-American (AA) versus Caucasian triple-negative breast cancer (TNBC).
O'Meara T, Yaghoobi V, Blenman K, Pelekanou V, Silber A, Rimm D, Pusztai L. Quantitative assessment of immune cell populations and associations with clinical outcomes in African-American (AA) versus Caucasian triple-negative breast cancer (TNBC). Journal Of Clinical Oncology 2019, 37: e14180-e14180. DOI: 10.1200/jco.2019.37.15_suppl.e14180.Peer-Reviewed Original ResearchTriple-negative breast cancerDisease-free survivalBetter disease-free survivalPD-L1 expressionCD68 expressionAA TNBCStromal PD-L1 expressionPD-L1 protein expressionCaucasian casesHigher TIL countsTumor immune microenvironmentImmune cell populationsHigh CD68 expressionHigh CD68Similar CD8Stromal TILsClinical characteristicsDiagnosis dateTIL countPD-L1Clinical outcomesPredictive factorsCD8 expressionClinical variablesImmune microenvironment
2018
An assessment of neuronal calcium sensor-1 and response to neoadjuvant chemotherapy in breast cancer patients
Moore LM, Wilkinson R, Altan M, Toki M, Carvajal-Hausdorf DE, McGuire J, Ehrlich BE, Rimm DL. An assessment of neuronal calcium sensor-1 and response to neoadjuvant chemotherapy in breast cancer patients. Npj Breast Cancer 2018, 4: 6. PMID: 29560416, PMCID: PMC5847580, DOI: 10.1038/s41523-018-0057-7.Peer-Reviewed Original ResearchTaxane-based neoadjuvant chemotherapyPathological complete responseNeuronal calcium sensor-1Neoadjuvant chemotherapyNCS-1 expressionBreast cancer patientsPoor clinical outcomeEfficacy of paclitaxelBreast cancer biopsiesComplete responseClinical outcomesCancer patientsPredictive biomarkersBreast cancerCancer biopsiesChemotherapyElevated expressionPaclitaxelPrevious studiesResponseBiopsyPatientsExpressionTaxanesCancer
2017
Calcium Sensor, NCS-1, Promotes Tumor Aggressiveness and Predicts Patient Survival
Moore LM, England A, Ehrlich BE, Rimm DL. Calcium Sensor, NCS-1, Promotes Tumor Aggressiveness and Predicts Patient Survival. Molecular Cancer Research 2017, 15: 942-952. PMID: 28275088, PMCID: PMC5500411, DOI: 10.1158/1541-7786.mcr-16-0408.Peer-Reviewed Original ResearchConceptsBreast cancer cellsNCS-1Breast cancer patient cohortsNCS-1 expressionLymph node statusCancer cellsShorter survival rateIndependent breast cancer cohortsCancer patient cohortsBreast cancer cohortMB-231 breast cancer cellsPaclitaxel-induced cell deathAggressive tumor phenotypeNeuronal model systemClinical outcomesClinicopathologic featuresNeuronal calcium sensor-1Node statusPatient cohortProgesterone receptorWorse outcomesBreast cancerCalcium-binding proteinsCancer cohortEstrogen receptorWhole-exome sequencing and immune profiling of early-stage lung adenocarcinoma with fully annotated clinical follow-up
Kadara H, Choi M, Zhang J, Parra ER, Rodriguez-Canales J, Gaffney SG, Zhao Z, Behrens C, Fujimoto J, Chow C, Yoo Y, Kalhor N, Moran C, Rimm D, Swisher S, Gibbons DL, Heymach J, Kaftan E, Townsend JP, Lynch TJ, Schlessinger J, Lee J, Lifton RP, Wistuba II, Herbst RS. Whole-exome sequencing and immune profiling of early-stage lung adenocarcinoma with fully annotated clinical follow-up. Annals Of Oncology 2017, 28: 75-82. PMID: 27687306, PMCID: PMC5982809, DOI: 10.1093/annonc/mdw436.Peer-Reviewed Original ResearchConceptsRecurrence-free survivalPoor recurrence-free survivalWhole-exome sequencingEarly-stage lung adenocarcinomaMutant lung adenocarcinomaLung adenocarcinomaImmune markersClinical outcomesExact testNatural killer cell infiltrationProportional hazards regression modelsGranzyme B levelsImmune marker analysisImmune profiling analysisPD-L1 expressionImmune-based therapiesTumoral PD-L1Hazards regression modelsKRAS mutant tumorsNormal lung tissuesMajority of deathsFisher's exact testHigh mutation burdenAnalysis of immunophenotypeRelevant molecular markersMutation profiles in early-stage lung squamous cell carcinoma with clinical follow-up and correlation with markers of immune function
Choi M, Kadara H, Zhang J, Parra ER, Rodriguez-Canales J, Gaffney SG, Zhao Z, Behrens C, Fujimoto J, Chow C, Kim K, Kalhor N, Moran C, Rimm D, Swisher S, Gibbons DL, Heymach J, Kaftan E, Townsend JP, Lynch TJ, Schlessinger J, Lee J, Lifton RP, Herbst RS, Wistuba II. Mutation profiles in early-stage lung squamous cell carcinoma with clinical follow-up and correlation with markers of immune function. Annals Of Oncology 2017, 28: 83-89. PMID: 28177435, PMCID: PMC6246501, DOI: 10.1093/annonc/mdw437.Peer-Reviewed Original ResearchConceptsLung squamous cell carcinomaEarly stage lung squamous cell carcinomaNon-small cell lung cancerSquamous cell carcinomaWhole-exome sequencingImmune markersClinical outcomesCell carcinomaPIK3CA mutationsExact testPoor recurrence-free survivalProportional hazards regression modelsTumoral PD-L1 expressionPD-L1 expressionRecurrence-free survivalCell lung cancerComprehensive immune profilingTP53 mutant tumorsHazards regression modelsNormal lung tissuesFisher's exact testLUSC cohortAdjuvant therapyImmune profilingPoor prognosis
2016
Copy Number Changes Are Associated with Response to Treatment with Carboplatin, Paclitaxel, and Sorafenib in Melanoma
Wilson MA, Zhao F, Khare S, Roszik J, Woodman SE, D'Andrea K, Wubbenhorst B, Rimm DL, Kirkwood JM, Kluger HM, Schuchter LM, Lee SJ, Flaherty KT, Nathanson KL. Copy Number Changes Are Associated with Response to Treatment with Carboplatin, Paclitaxel, and Sorafenib in Melanoma. Clinical Cancer Research 2016, 22: 374-382. PMID: 26307133, PMCID: PMC4821426, DOI: 10.1158/1078-0432.ccr-15-1162.Peer-Reviewed Original ResearchMeSH KeywordsAntineoplastic Combined Chemotherapy ProtocolsCarboplatinDisease-Free SurvivalDNA Copy Number VariationsDNA Mutational AnalysisDouble-Blind MethodGenes, rasHumansMelanomaMutationNeoplasm StagingNiacinamidePaclitaxelPhenylurea CompoundsProto-Oncogene Proteins B-rafProto-Oncogene Proteins c-metSorafenibTreatment OutcomeConceptsProgression-free survivalGene copy gainOverall survivalImproved progression-free survivalCopy gainImproved overall survivalGenomic alterationsCancer Genome Atlas (TCGA) datasetImproved treatment responseClinical outcomesMET amplificationV600KCCND1 amplificationTreatment responseMelanoma pathogenesisV600E mutationCurrent FDAPretreatment samplesBRAF geneTumor samplesPatientsSorafenibTherapyTumorsAtlas dataset
2014
EGFR expression is associated with decreased benefit from trastuzumab in the NCCTG N9831 (Alliance) trial
Cheng H, Ballman K, Vassilakopoulou M, Dueck AC, Reinholz MM, Tenner K, Gralow J, Hudis C, Davidson NE, Fountzilas G, McCullough AE, Chen B, Psyrri A, Rimm DL, Perez EA. EGFR expression is associated with decreased benefit from trastuzumab in the NCCTG N9831 (Alliance) trial. British Journal Of Cancer 2014, 111: 1065-1071. PMID: 25117817, PMCID: PMC4453859, DOI: 10.1038/bjc.2014.442.Peer-Reviewed Original ResearchConceptsNorth Central Cancer Treatment GroupMetastatic breast cancer cohortEpidermal growth factor receptorBreast cancer cohortHigh EGFR expressionEGFR expressionConcurrent trastuzumabGrowth factor receptorCancer cohortEGFR antibodyNCCTG N9831 trialsAnti-HER2 therapyCancer Treatment GroupDisease-free survivalFactor receptorN9831 trialsSequential trastuzumabAdditive therapyArm AClinical outcomesTreatment optionsWorse outcomesArm CTissue microarrayTreatment groupsCorrelation of Somatic Mutations and Clinical Outcome in Melanoma Patients Treated with Carboplatin, Paclitaxel, and Sorafenib
Wilson MA, Zhao F, Letrero R, D'Andrea K, Rimm DL, Kirkwood JM, Kluger HM, Lee SJ, Schuchter LM, Flaherty KT, Nathanson KL. Correlation of Somatic Mutations and Clinical Outcome in Melanoma Patients Treated with Carboplatin, Paclitaxel, and Sorafenib. Clinical Cancer Research 2014, 20: 3328-3337. PMID: 24714776, PMCID: PMC4058354, DOI: 10.1158/1078-0432.ccr-14-0093.Peer-Reviewed Original ResearchMeSH KeywordsAdultAntineoplastic Combined Chemotherapy ProtocolsBiomarkers, TumorCarboplatinDouble-Blind MethodFemaleFollow-Up StudiesGenotypeGTP PhosphohydrolasesHumansMaleMelanomaMembrane ProteinsMiddle AgedMutationNeoplasm StagingNiacinamidePaclitaxelPhenylurea CompoundsPrognosisProto-Oncogene Proteins B-rafSkin NeoplasmsSorafenibSurvival RateConceptsProgression-free survivalNRAS-mutant melanomaPlatelet-derived growth factor receptorPerformance statusClinical outcomesNRAS mutationsCox proportional hazards modelVEGF receptorsSomatic mutationsWorse performance statusGood performance statusImproved clinical responseKaplan-Meier methodClinical trial populationsPretreatment tumor samplesSite of diseaseProportional hazards modelEffect of sorafenibBRAF-mutant melanomaFisher's exact testGrowth factor receptorClinical responseOverall survivalClinicopathologic featuresMelanoma patients
2013
Effect of PDL-1 expression on prognosis in head and neck squamous cell carcinoma.
Vasilakopoulou M, Velcheti V, Rampias T, Sasaki C, Rimm D, Fountzilas G, Psyrri A. Effect of PDL-1 expression on prognosis in head and neck squamous cell carcinoma. Journal Of Clinical Oncology 2013, 31: 6012-6012. DOI: 10.1200/jco.2013.31.15_suppl.6012.Peer-Reviewed Original ResearchPDL-1 expressionPDL-1Prognostic significanceT cellsMultivariate Cox proportional hazards modelCox proportional hazards modelNeck squamous cell carcinomaDeath-1 receptorFavorable clinical outcomeKaplan-Meier methodInduces tumor regressionSquamous cell carcinomaHNSCC tissue microarrayLog-rank testProportional hazards modelProtein expression levelsImproved DFSEfficacy outcomesImmunotherapeutic approachesClinical outcomesMultivariable analysisEntire cohortCell carcinomaCancer patientsFavorable outcome
2012
Low levels of Stat5a protein in breast cancer are associated with tumor progression and unfavorable clinical outcomes
Peck AR, Witkiewicz AK, Liu C, Klimowicz AC, Stringer GA, Pequignot E, Freydin B, Yang N, Ertel A, Tran TH, Girondo MA, Rosenberg AL, Hooke JA, Kovatich AJ, Shriver CD, Rimm DL, Magliocco AM, Hyslop T, Rui H. Low levels of Stat5a protein in breast cancer are associated with tumor progression and unfavorable clinical outcomes. Breast Cancer Research 2012, 14: r130. PMID: 23036105, PMCID: PMC4053108, DOI: 10.1186/bcr3328.Peer-Reviewed Original ResearchConceptsPoor prognosisBreast cancerClinical outcomesIndependent markerNode-negative breast cancer patientsNode-negative breast cancerLower tumor levelsPrimary breast cancerUnfavorable clinical outcomeBreast cancer patientsClinical outcome dataProtein levelsRandomized clinical trialsPredictors of responseNew independent markerBreast cancer progressionTherapy-naïveFourfold riskCancer patientsTherapy failureTumor levelsArchival cohortUnfavorable outcomeClinical trialsStat5a/bLin28 regulates HER2 and promotes malignancy through multiple mechanisms
Feng C, Neumeister V, Ma W, Xu J, Lu L, Bordeaux J, Maihle NJ, Rimm DL, Huang Y. Lin28 regulates HER2 and promotes malignancy through multiple mechanisms. Cell Cycle 2012, 11: 2486-2494. PMID: 22713243, DOI: 10.4161/cc.20893.Peer-Reviewed Original ResearchConceptsHuman epidermal growth factor receptor 2HER2 expressionLin28 expressionEpidermal growth factor receptor 2Growth factor receptor 2Primary breast tumorsFactor receptor 2Cancer cell growthMajor therapeutic targetMultiple mechanismsAdvanced human malignanciesClinical outcomesPoor prognosisBreast cancerReceptor 2Therapeutic targetBreast tumorsNovel mechanistic insightsHuman malignanciesLin28 overexpressionReceptor tyrosine kinasesCancerCell proliferationHuman cancersPowerful predictor
2011
Loss of Nuclear Localized and Tyrosine Phosphorylated Stat5 in Breast Cancer Predicts Poor Clinical Outcome and Increased Risk of Antiestrogen Therapy Failure
Peck AR, Witkiewicz AK, Liu C, Stringer GA, Klimowicz AC, Pequignot E, Freydin B, Tran TH, Yang N, Rosenberg AL, Hooke JA, Kovatich AJ, Nevalainen MT, Shriver CD, Hyslop T, Sauter G, Rimm DL, Magliocco AM, Rui H. Loss of Nuclear Localized and Tyrosine Phosphorylated Stat5 in Breast Cancer Predicts Poor Clinical Outcome and Increased Risk of Antiestrogen Therapy Failure. Journal Of Clinical Oncology 2011, 29: 2448-2458. PMID: 21576635, PMCID: PMC3675698, DOI: 10.1200/jco.2010.30.3552.Peer-Reviewed Original ResearchMeSH KeywordsAdultAgedAged, 80 and overAntineoplastic Agents, HormonalBreast NeoplasmsCarcinoma, Ductal, BreastCarcinoma, Intraductal, NoninfiltratingCohort StudiesDisease ProgressionDisease-Free SurvivalDrug Resistance, NeoplasmEstrogen Receptor ModulatorsFemaleHumansLymphatic MetastasisMiddle AgedNeoplasm ProteinsNuclear ProteinsPhosphorylationPhosphotyrosinePrognosisProtein Processing, Post-TranslationalSTAT5 Transcription FactorSurvival AnalysisTreatment FailureTumor Suppressor ProteinsYoung AdultConceptsNode-negative breast cancerCancer-specific survivalIndependent prognostic markerBreast cancerWhole tissue sectionsTherapy failurePrognostic markerTissue microarrayPathologist scoringMultivariate analysis patientsSystemic adjuvant therapyAdjuvant hormone therapyMarker of prognosisPoor clinical outcomeUseful predictive markerPredictors of responseNormal breast epitheliumTissue sectionsCohort IVAdjuvant therapyHormone therapyAnalysis patientsClinical outcomesDuctal carcinomaProspective studyDifferential expression of arrestins is a predictor of breast cancer progression and survival
Michal AM, Peck AR, Tran TH, Liu C, Rimm DL, Rui H, Benovic JL. Differential expression of arrestins is a predictor of breast cancer progression and survival. Breast Cancer Research And Treatment 2011, 130: 791-807. PMID: 21318602, PMCID: PMC3156829, DOI: 10.1007/s10549-011-1374-9.Peer-Reviewed Original ResearchConceptsBreast cancer progressionBreast cancerCancer progressionArrestin2 expressionLuminal linesMyoepithelial cellsNormal human breast tissueMetastatic breast cancerLymph node metastasisPoor clinical outcomeIndependent prognostic markerPrimary breast tumorsBreast cancer cell linesG protein-coupled receptorsArrestin2 levelsPositive lymphCancer cell linesHazard ratioHuman breast tissueProtein-coupled receptorsNode metastasisClinical outcomesDuctal carcinomaTumor sizeNuclear grade