2023
Deep learning-based scoring of tumour-infiltrating lymphocytes is prognostic in primary melanoma and predictive to PD-1 checkpoint inhibition in melanoma metastases
Chatziioannou E, Roßner J, Aung T, Rimm D, Niessner H, Keim U, Serna-Higuita L, Bonzheim I, Cuellar L, Westphal D, Steininger J, Meier F, Pop O, Forchhammer S, Flatz L, Eigentler T, Garbe C, Röcken M, Amaral T, Sinnberg T. Deep learning-based scoring of tumour-infiltrating lymphocytes is prognostic in primary melanoma and predictive to PD-1 checkpoint inhibition in melanoma metastases. EBioMedicine 2023, 93: 104644. PMID: 37295047, PMCID: PMC10363450, DOI: 10.1016/j.ebiom.2023.104644.Peer-Reviewed Original ResearchMeSH KeywordsDeep LearningHumansLymphocytes, Tumor-InfiltratingMelanomaNeoplasm Recurrence, LocalPrognosisSkin NeoplasmsConceptsTumor-infiltrating lymphocytesMultiple Cox regressionMelanoma-specific survivalCox regressionTumor thicknessCutaneous melanomaPrimary melanomaAssessment of TILsPD-1 checkpoint inhibitionSignificant unfavourable prognostic factorLonger progression-free survivalDistant metastasis-free survivalSimple Cox regressionUnfavourable survival outcomeFirst-line therapyProgression-free survivalUnfavourable prognostic factorCutaneous melanoma patientsMetastasis-free survivalPresence of ulcerationPrimary cutaneous melanomaCox regression modelPrimary melanoma samplesPrimary tissuesOverall survivalDigital spatial profiling links beta-2-microglobulin expression with immune checkpoint blockade outcomes in head and neck squamous cell carcinoma
Gavrielatou N, Vathiotis I, Aung T, Shafi S, Burela S, Fernandez A, Moutafi M, Burtness B, Economopoulou P, Anastasiou M, Foukas P, Psyrri A, Rimm D. Digital spatial profiling links beta-2-microglobulin expression with immune checkpoint blockade outcomes in head and neck squamous cell carcinoma. Cancer Research Communications 2023, 3: 558-563. PMID: 37057033, PMCID: PMC10088911, DOI: 10.1158/2767-9764.crc-22-0299.Peer-Reviewed Original ResearchMeSH KeywordsCarcinomaHead and Neck NeoplasmsHumansImmune Checkpoint InhibitorsNeoplasm Recurrence, LocalSquamous Cell Carcinoma of Head and NeckConceptsDigital spatial profilingB2M expressionOverall survivalM HNSCCImmunotherapy outcomesNeck squamous cell carcinoma (HNSCC) treatmentHigh beta-2 microglobulinSquamous cell carcinoma treatmentCell death protein 1Neck squamous cell carcinomaM expressionPretreatment biopsy samplesImmune checkpoint inhibitorsPD-L1 expressionImmune checkpoint markersDeath protein 1Squamous cell carcinomaB2MBeta-2-microglobulinBeta 2 microglobulin expressionImproved PFSCheckpoint inhibitorsMetastatic headCheckpoint markersImproved survival
2019
Deep Learning Based on Standard H&E Images of Primary Melanoma Tumors Identifies Patients at Risk for Visceral Recurrence and Death
Kulkarni PM, Robinson EJ, Pradhan J, Gartrell-Corrado RD, Rohr BR, Trager MH, Geskin LJ, Kluger HM, Wong PF, Acs B, Rizk EM, Yang C, Mondal M, Moore MR, Osman I, Phelps R, Horst BA, Chen ZS, Ferringer T, Rimm DL, Wang J, Saenger YM. Deep Learning Based on Standard H&E Images of Primary Melanoma Tumors Identifies Patients at Risk for Visceral Recurrence and Death. Clinical Cancer Research 2019, 26: 1126-1134. PMID: 31636101, PMCID: PMC8142811, DOI: 10.1158/1078-0432.ccr-19-1495.Peer-Reviewed Original ResearchMeSH KeywordsAdultAgedAged, 80 and overAlgorithmsArea Under CurveBiopsyDeep LearningDisease ProgressionFemaleFollow-Up StudiesHumansImage Processing, Computer-AssistedMaleMelanomaMiddle AgedNeoplasm Recurrence, LocalNeural Networks, ComputerRetrospective StudiesRisk FactorsStaining and LabelingSurvival RateYoung AdultConceptsDeep neural network architectureNeural network architectureDeep learningNetwork architectureComputational modelImage sequencesDigital imagesVote aggregationDisease-specific survivalDSS predictionPractical advancesComputational methodsIHC-based methodsImagesGeisinger Health SystemNovel methodGHS patientsArchitectureLearningKaplan-Meier analysisPrimary melanoma tumorsEarly-stage melanomaClinical trial designModelAdjuvant immunotherapyMultiplexed (18-Plex) Measurement of Signaling Targets and Cytotoxic T Cells in Trastuzumab-Treated Patients using Imaging Mass Cytometry
Carvajal-Hausdorf DE, Patsenker J, Stanton KP, Villarroel-Espindola F, Esch A, Montgomery RR, Psyrri A, Kalogeras KT, Kotoula V, Foutzilas G, Schalper KA, Kluger Y, Rimm DL. Multiplexed (18-Plex) Measurement of Signaling Targets and Cytotoxic T Cells in Trastuzumab-Treated Patients using Imaging Mass Cytometry. Clinical Cancer Research 2019, 25: 3054-3062. PMID: 30796036, PMCID: PMC6522272, DOI: 10.1158/1078-0432.ccr-18-2599.Peer-Reviewed Original ResearchConceptsTrastuzumab-treated patientsT cell infiltrationCD8 T cell infiltrationCohort of patientsCytotoxic T cellsMass cytometryCase-control seriesExtracellular domainMechanism of actionTrastuzumab benefitAdjuvant treatmentCD8 cellsRecurrence eventsT cellsAntibody panelImmune systemPatientsMetal-conjugated antibodiesQuantitative immunofluorescenceTrastuzumabImaging Mass CytometryHER2Signaling targetsObjective measurementsCytometry
2015
Development and Clinical Validation of an In Situ Biopsy-Based Multimarker Assay for Risk Stratification in Prostate Cancer
Blume-Jensen P, Berman DM, Rimm DL, Shipitsin M, Putzi M, Nifong TP, Small C, Choudhury S, Capela T, Coupal L, Ernst C, Hurley A, Kaprelyants A, Chang H, Giladi E, Nardone J, Dunyak J, Loda M, Klein EA, Magi-Galluzzi C, Latour M, Epstein JI, Kantoff P, Saad F. Development and Clinical Validation of an In Situ Biopsy-Based Multimarker Assay for Risk Stratification in Prostate Cancer. Clinical Cancer Research 2015, 21: 2591-2600. PMID: 25733599, DOI: 10.1158/1078-0432.ccr-14-2603.Peer-Reviewed Original ResearchConceptsBiomarker risk scoreRisk scoreRisk groupsPredictive valueNational Comprehensive Cancer NetworkComprehensive Cancer NetworkCurrent risk stratification systemsIndependent prognostic informationRisk stratification systemProstate cancer aggressivenessRisk classification groupsAccurate risk predictionCoprimary endpointsFavorable pathologyAppropriate therapyCurative therapyRisk stratificationPathologic parametersPrognostic informationProstate biopsyProstate pathologyProstate cancerBlinded studyProstatectomy specimensCancer Network
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 Analysis
2013
Prediction of Late Disease Recurrence and Extended Adjuvant Letrozole Benefit by the HOXB13/IL17BR Biomarker
Sgroi DC, Carney E, Zarrella E, Steffel L, Binns SN, Finkelstein DM, Szymonifka J, Bhan AK, Shepherd LE, Zhang Y, Schnabel CA, Erlander MG, Ingle JN, Porter P, Muss HB, Pritchard KI, Tu D, Rimm DL, Goss PE. Prediction of Late Disease Recurrence and Extended Adjuvant Letrozole Benefit by the HOXB13/IL17BR Biomarker. Journal Of The National Cancer Institute 2013, 105: 1036-1042. PMID: 23812955, PMCID: PMC3888138, DOI: 10.1093/jnci/djt146.Peer-Reviewed Original ResearchMeSH KeywordsAdultAgedAntineoplastic AgentsAromatase InhibitorsBiomarkers, TumorBreast NeoplasmsCase-Control StudiesChemotherapy, AdjuvantDisease-Free SurvivalFemaleHomeodomain ProteinsHumansIncidenceLetrozoleLogistic ModelsMiddle AgedMultivariate AnalysisNeoplasm GradingNeoplasm Recurrence, LocalNeoplasm StagingNitrilesPredictive Value of TestsPrognosisProspective StudiesReceptor, ErbB-2Receptors, EstrogenReceptors, InterleukinReceptors, Interleukin-17Receptors, ProgesteroneRetrospective StudiesReverse Transcriptase Polymerase Chain ReactionTriazolesConceptsExtended letrozole therapyStandard clinicopathological factorsLate disease recurrenceLate recurrenceLetrozole therapyEndocrine therapyDisease recurrenceClinicopathological factorsLymph node-negative breast cancer patientsNode-negative breast cancer patientsExtended adjuvant endocrine therapyMultivariable conditional logistic regressionExtended adjuvant letrozolePlacebo-treated patientsAdjuvant endocrine therapyER-positive patientsBreast cancer patientsPositive breast cancerConditional logistic regressionReverse transcription-polymerase chain reactionCase-control designAdjuvant letrozoleLetrozole treatmentAbsolute riskCancer patientsHigh Frequency of Putative Ovarian Cancer Stem Cells With CD44/CK19 Coexpression Is Associated With Decreased Progression-Free Intervals In Patients With Recurrent Epithelial Ovarian Cancer
Liu M, Mor G, Cheng H, Xiang X, Hui P, Rutherford T, Yin G, Rimm DL, Holmberg J, Alvero A, Silasi DA. High Frequency of Putative Ovarian Cancer Stem Cells With CD44/CK19 Coexpression Is Associated With Decreased Progression-Free Intervals In Patients With Recurrent Epithelial Ovarian Cancer. Reproductive Sciences 2013, 20: 605-615. PMID: 23171677, PMCID: PMC3635069, DOI: 10.1177/1933719112461183.Peer-Reviewed Original ResearchMeSH KeywordsAdultAgedAged, 80 and overAnalysis of VarianceBiomarkers, TumorCarcinoma, Ovarian EpithelialDisease ProgressionDisease-Free SurvivalDrug Resistance, NeoplasmFemaleHumansHyaluronan ReceptorsKaplan-Meier EstimateKeratin-19Middle AgedMultivariate AnalysisNeoplasm Recurrence, LocalNeoplasm StagingNeoplasms, Glandular and EpithelialNeoplastic Stem CellsOvarian NeoplasmsProportional Hazards ModelsRetrospective StudiesRisk FactorsTime FactorsTreatment OutcomeConceptsPutative ovarian cancer stem cellsOvarian cancer stem cellsProgression-free intervalCancer stem cellsRecurrent epithelial ovarian cancerShorter disease-free intervalShorter progression-free intervalDisease-free intervalResidual tumor volumeEpithelial ovarian cancerLog-rank testEpithelial ovarian cancer cellsIndependent significant predictorsAdvanced stage EOCOvarian cancer cellsStem cellsMean followObstetrics stageUnivariable analysisClinicopathologic featuresMultivariable analysisRetrospective studyPrognostic valueOvarian cancerTumor volume
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/b
2007
Phosphorylation of Akt (Ser473) Predicts Poor Clinical Outcome in Oropharyngeal Squamous Cell Cancer
Yu Z, Weinberger PM, Sasaki C, Egleston BL, Speier WF, Haffty B, Kowalski D, Camp R, Rimm D, Vairaktaris E, Burtness B, Psyrri A. Phosphorylation of Akt (Ser473) Predicts Poor Clinical Outcome in Oropharyngeal Squamous Cell Cancer. Cancer Epidemiology Biomarkers & Prevention 2007, 16: 553-558. PMID: 17372251, DOI: 10.1158/1055-9965.epi-06-0121.Peer-Reviewed Original ResearchMeSH KeywordsAdultAgedBiomarkers, TumorCarcinoma, Squamous CellChi-Square DistributionFemaleHumansImmunoenzyme TechniquesMaleMiddle AgedNeoplasm Recurrence, LocalOropharyngeal NeoplasmsPhosphorylationPredictive Value of TestsPrognosisProportional Hazards ModelsProtein Array AnalysisProto-Oncogene Proteins c-aktPTEN PhosphohydrolaseSurvival AnalysisConceptsNuclear p-AktAkt activationP-AktOropharyngeal squamous cell cancerSquamous cell carcinoma progressionPhosphorylated AktCohort of patientsLocal recurrence rateOverall survival rateSquamous cell cancerPoor clinical outcomeAdverse patient outcomesP-AKT levelsPromising molecular targetP-AKT expressionProtein expression levelsPhosphorylation of AktDisease recurrenceLocal recurrenceCell cancerClinical outcomesAdjusted analysisPrognostic significanceRecurrence ratePatient outcomes
2005
Immunohistochemical Biomarkers in Patients with Early-Onset Breast Carcinoma by Tissue Microarray
Choi DH, Kim S, Rimm DL, Carter D, Haffty BG. Immunohistochemical Biomarkers in Patients with Early-Onset Breast Carcinoma by Tissue Microarray. The Cancer Journal 2005, 11: 404-411. PMID: 16259871, DOI: 10.1097/00130404-200509000-00008.Peer-Reviewed Original ResearchMeSH KeywordsAdenocarcinoma, MucinousAdultBiomarkers, TumorBreast NeoplasmsDisease-Free SurvivalFemaleFollow-Up StudiesHumansImmunohistochemistryKi-67 AntigenMiddle AgedMultivariate AnalysisNeoplasm Recurrence, LocalNeoplasms, Ductal, Lobular, and MedullaryProtein Array AnalysisProto-Oncogene Proteins c-bcl-2Receptor, ErbB-2Receptors, EstrogenReceptors, ProgesteroneTime FactorsTumor Suppressor Protein p53Women's HealthConceptsHER-2/neuBreast cancerProgesterone receptorKi-67Local relapseNodal statusYoung womenDistant metastasisTumor stageBiologic markersEstrogen receptorRelapse-free survival rateDistant metastasis-free rateDistant relapse-free survival ratesEarly-stage breast cancerEarly-onset breast cancerEarly-onset breast carcinomaProgesterone receptor negativityGroup of patientsMetastasis-free rateBcl-2Ki-67 positivityParaffin-embedded specimensTissue microarray methodConservative surgeryUpstaging 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 diseaseCyclin D1 Is a Valuable Prognostic Marker in Oropharyngeal Squamous Cell Carcinoma
Yu Z, Weinberger PM, Haffty BG, Sasaki C, Zerillo C, Joe J, Kowalski D, Dziura J, Camp RL, Rimm DL, Psyrri A. Cyclin D1 Is a Valuable Prognostic Marker in Oropharyngeal Squamous Cell Carcinoma. Clinical Cancer Research 2005, 11: 1160-1166. PMID: 15709184, DOI: 10.1158/1078-0432.1160.11.3.Peer-Reviewed Original ResearchConceptsOropharyngeal squamous cell carcinomaDisease-free survivalSquamous cell carcinomaCyclin D1Overall survivalCell carcinomaPrognostic markerOropharyngeal squamous cell cancerProtein expressionLocal recurrence rateMultivariate Cox regressionLong-term followSquamous cell cancerCyclin D1 expression levelsNuclear cyclin D1 expressionTerms of prognosisCell cycle regulator cyclin D1Valuable prognostic markerExpression levelsCyclin D1 expressionProtein expression levelsMean followIndependent predictorsLocal recurrenceCell cancer
2004
Prognostic Significance of p16 Protein Levels in Oropharyngeal Squamous Cell Cancer
Weinberger PM, Yu Z, Haffty BG, Kowalski D, Harigopal M, Sasaki C, Rimm DL, Psyrri A. Prognostic Significance of p16 Protein Levels in Oropharyngeal Squamous Cell Cancer. Clinical Cancer Research 2004, 10: 5684-5691. PMID: 15355894, DOI: 10.1158/1078-0432.ccr-04-0448.Peer-Reviewed Original ResearchConceptsSquamous cell cancerOropharyngeal squamous cell carcinomaOropharyngeal squamous cell cancerDisease-free survivalLocal recurrence rateSquamous cell carcinomaCell cancerOverall survivalRecurrence rateCell carcinomaP16 overexpressionNeck squamous cell cancerLow local recurrence rateAdvanced Tumor-NodeMean patient followIndependent prognostic factorHigh histologic gradeP16 expression statusOverexpression of p16Local recurrencePrognostic factorsPrognostic importanceP16 protein expressionPrognostic significanceHistologic gradeMolecular 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 ResearchMeSH KeywordsAdultAgedBiomarkersBreast NeoplasmsCarcinomaFemaleHumansMastectomyMiddle AgedNeoplasm MetastasisNeoplasm Recurrence, LocalPrognosisRetrospective StudiesThoracic WallConceptsHER-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
2003
BRCA Status, Molecular Markers, and Clinical Variables in Early, Conservatively Managed Breast Cancer
Kim S, Rimm D, Carter D, Khan A, Parisot N, Franco MA, Bale A, Haffty BG. BRCA Status, Molecular Markers, and Clinical Variables in Early, Conservatively Managed Breast Cancer. The Breast Journal 2003, 9: 167-174. PMID: 12752624, DOI: 10.1046/j.1524-4741.2003.09307.x.Peer-Reviewed Original ResearchMeSH KeywordsAdultBiomarkers, TumorBRCA1 ProteinBRCA2 ProteinBreast NeoplasmsCohort StudiesFemaleGenetic Predisposition to DiseaseHumansImmunohistochemistryMutationNeoplasm Recurrence, LocalPremenopauseProliferating Cell Nuclear AntigenReceptor, ErbB-2Receptors, EstrogenReceptors, ProgesteroneTumor Suppressor Protein p53ConceptsHER-2/neuEstrogen receptorProgesterone receptorBRCA-1BRCA-2Breast cancerBRCA mutationsProliferating Cell Nuclear AntigenMolecular biologic markersPremenopausal breast cancerBRCA-1 mutationsBreast-conserving surgeryWide local excisionBreast cancer patientsPrimary breast tumor tissuesAvailable paraffin blocksBRCA-2 genesBreast tumor tissuesFamilial breast cancerCell nuclear antigenAxillary dissectionPR negativityPremenopausal womenLocal relapseSystemic therapy