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 benefitsPatientsCD68An algorithm for standardization of tumor Infiltrating lymphocyte evaluation in head and neck cancers
Xirou V, Moutafi M, Bai Y, Nwe Aung T, Burela S, Liu M, Kimple R, Shabbir Ahmed F, Schultz B, Flieder D, Connolly D, Psyrri A, Burtness B, Rimm D. An algorithm for standardization of tumor Infiltrating lymphocyte evaluation in head and neck cancers. Oral Oncology 2024, 152: 106750. PMID: 38547779, PMCID: PMC11060915, DOI: 10.1016/j.oraloncology.2024.106750.Peer-Reviewed Original ResearchConceptsTumor-infiltrating lymphocytesHead and neck cancerTILs evaluationHPV-positiveNeck cancerPrognostic valueHead and neck squamous cell cancer casesTIL variablesAssociated with favorable prognosisHPV-negative headHPV-negative populationHematoxylin-eosin-stained sectionsCox regression analysisPotential clinical implicationsInter-observer variabilityInfiltrating lymphocytesClinicopathological factorsFavorable prognosisValidation cohortTumor cellsCancer casesProspective settingQuPath softwareRetrospective collectionPredictive significance
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 studiesClassification of Breast Cancer According to ERBB2 Immunohistochemistry Scores
Robbins C, Fernandez A, Rimm D. Classification of Breast Cancer According to ERBB2 Immunohistochemistry Scores. JAMA Oncology 2023, 9: 1298-1299. PMID: 37498606, DOI: 10.1001/jamaoncol.2023.2635.Commentaries, Editorials and LettersAssessment of the Impact of Alternative Fixatives on HER2 Detection in Breast Cancer and Gastric Cancer Tumor Specimens
Feng W, Inoue R, Kuwata T, Niikura N, Fujii S, Kumaki N, Honda K, Xu L, Goetz A, Gaule P, Cogswell J, Rimm D, McGee R. Assessment of the Impact of Alternative Fixatives on HER2 Detection in Breast Cancer and Gastric Cancer Tumor Specimens. Applied Immunohistochemistry & Molecular Morphology 2023, 31: 339-345. PMID: 37093713, PMCID: PMC10155692, DOI: 10.1097/pai.0000000000001126.Peer-Reviewed Original ResearchConceptsNeutral buffered formalinNegative percentage agreementPositive percentage agreementOverall percentage agreementBreast cancerPercentage agreementHER2 statusHuman epidermal growth factor receptor 2 (HER2) statusEpidermal growth factor receptor 2 statusTumor samplesCell linesGastric cancer tumorsGastric cancer cell linesTumor tissue samplesClinical trial sitesCancer cell linesHER2 testingTumor specimensReal-world settingTumor tissueCancer tumorsBuffered formalinSitu hybridization assaysType of fixativeCentral laboratorySpatial characterization and quantification of CD40 expression across cancer types
Bates K, Vathiotis I, MacNeil T, Ahmed F, Aung T, Katlinskaya Y, Bhattacharya S, Psyrri A, Yea S, Parkes A, Sadraei N, Roychoudhury S, Rimm D, Gavrielatou N. Spatial characterization and quantification of CD40 expression across cancer types. BMC Cancer 2023, 23: 220. PMID: 36894898, PMCID: PMC9996913, DOI: 10.1186/s12885-023-10650-7.Peer-Reviewed Original ResearchConceptsCD40 expressionSolid tumorsTumor cellsQuantitative immunofluorescencePatient cohortPancreatic cancerCancer typesExpression of CD40Large patient cohortOvarian cancer populationTissue microarray formatDifferent solid tumorsInnate immune responseTNF receptor family membersAvailable patient cohortNSCLC populationOverall survivalPrognostic impactReceptor family membersCancer populationAdenocarcinoma populationImmune cellsOvarian cancerPancreatic adenocarcinomaPositivity rateMulti-institutional Assessment of Pathologist Scoring HER2 Immunohistochemistry
Robbins C, Fernandez A, Han G, Wong S, Harigopal M, Podoll M, Singh K, Ly A, Kuba M, Wen H, Sanders M, Brock J, Wei S, Fadare O, Hanley K, Jorns J, Snir O, Yoon E, Rabe K, Soong T, Reisenbichler E, Rimm D. Multi-institutional Assessment of Pathologist Scoring HER2 Immunohistochemistry. Modern Pathology 2023, 36: 100032. PMID: 36788069, PMCID: PMC10278086, DOI: 10.1016/j.modpat.2022.100032.Peer-Reviewed Original ResearchConceptsOverall percent agreementHuman epidermal growth factor 2HER2 IHCReal-world settingEpidermal growth factor 2HER2-negative statusBreast cancer biopsiesCompanion diagnostic testsMulti-institutional assessmentGrowth factor 2Breast cancerImmunohistochemistry assaysCancer biopsiesHER2 immunohistochemistryPathologist concordanceIHCClinical standardsPercent agreementDiagnostic testsSubstantial discordanceERBB2 geneInterrater reliabilityPathologistsFactor 2Concordance
2022
Quantitative measurement of HER2 expression to subclassify ERBB2 unamplified breast cancer.
Moutafi M, Robbins C, Yaghoobi V, Fernandez A, Martinez-Morilla S, Xirou V, Bai Y, Song Y, Gaule P, Krueger J, Bloom K, Hill S, Liebler D, Fulton R, Rimm D. Quantitative measurement of HER2 expression to subclassify ERBB2 unamplified breast cancer. Laboratory Investigation 2022, 102: 1101-1108. PMID: 36775350, DOI: 10.1038/s41374-022-00804-9.Peer-Reviewed Original ResearchConceptsHER2 expressionBreast cancerAttomol/HER2 proteinBreast cancer patientsBreast cancer casesOptimal patient careLevels of HER2Trastuzumab deruxtecanT-DXdCancer patientsLow HER2Cancer casesConventional assaysHER2Patient careAntibody concentrationsQuantitative immunofluorescenceAntibody drugsCancerCell linesAssaysExpressionHER2 detectionLower rangePredictive Markers of Response to Neoadjuvant Durvalumab with Nab-Paclitaxel and Dose-Dense Doxorubicin/Cyclophosphamide in Basal-Like Triple-Negative Breast Cancer.
Blenman KRM, Marczyk M, Karn T, Qing T, Li X, Gunasekharan V, Yaghoobi V, Bai Y, Ibrahim EY, Park T, Silber A, Wolf DM, Reisenbichler E, Denkert C, Sinn BV, Rozenblit M, Foldi J, Rimm DL, Loibl S, Pusztai L. Predictive Markers of Response to Neoadjuvant Durvalumab with Nab-Paclitaxel and Dose-Dense Doxorubicin/Cyclophosphamide in Basal-Like Triple-Negative Breast Cancer. Clinical Cancer Research 2022, 28: 2587-2597. PMID: 35377948, PMCID: PMC9464605, DOI: 10.1158/1078-0432.ccr-21-3215.Peer-Reviewed Original ResearchConceptsBasal-like triple-negative breast cancerPathologic complete responseResidual diseaseNeoadjuvant durvalumabDNA damage repairSomatic mutationsBreast cancerWnt/β-cateninHigh expressionTriple-negative breast cancerBasal-Like TripleDoxorubicin/cyclophosphamideDNA repairTumor mutation burdenRNA sequencingEpithelial-mesenchymal transitionFive-gene signatureB-cell markersCancer driversEnrichment analysisNegative breast cancerDamage repairGene expressionJAK-STATCell cycleExamination of Low ERBB2 Protein Expression in Breast Cancer Tissue
Fernandez AI, Liu M, Bellizzi A, Brock J, Fadare O, Hanley K, Harigopal M, Jorns JM, Kuba MG, Ly A, Podoll M, Rabe K, Sanders MA, Singh K, Snir OL, Soong TR, Wei S, Wen H, Wong S, Yoon E, Pusztai L, Reisenbichler E, Rimm DL. Examination of Low ERBB2 Protein Expression in Breast Cancer Tissue. JAMA Oncology 2022, 8: 1-4. PMID: 35113160, PMCID: PMC8814969, DOI: 10.1001/jamaoncol.2021.7239.Peer-Reviewed Original ResearchConceptsBreast cancer biopsiesT-DXdCancer biopsiesLarge randomized clinical trialsRandomized clinical trialsERBB2 protein expressionCentral pathology laboratoryBreast cancer tissuesAmerican Pathologists surveysStudy of concordanceTrastuzumab deruxtecanERBB2 positivityPatient populationClinical trialsScore 0Breast cancerImmunohistochemistry scoreCancer tissuesIHC assaysPatientsPathology laboratoryProtein expressionBiopsyIHCConcordanceCECR2 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 tumorsMetastasisThe Effect of Black Cohosh on Ki67 expression and Tumor Volume: A Pilot Study of Ductal Carcinoma in Situ Patients
Trant A, Chagpar A, Wei W, Neumeister V, Rimm D, Stavris K, Lurie B, Frederick C, Andrejeva L, Raghu M, Killelea B, Horowitz N, Lannin D, Knill-Selby E, Sturrock T, Hofstatter E. The Effect of Black Cohosh on Ki67 expression and Tumor Volume: A Pilot Study of Ductal Carcinoma in Situ Patients. Integrative Cancer Therapies 2022, 21: 15347354221137290. PMID: 36444764, PMCID: PMC9716631, DOI: 10.1177/15347354221137290.Peer-Reviewed Original ResearchConceptsTumor volumeBlack cohoshSitu patientsDuctal carcinomaAnti-inflammatory effectsTumor cellular proliferationBreast cancer treatmentCellular proliferationWilcoxon signed-rank testDCIS patientsAdverse eventsEligible subjectsWindow trialsCore biopsyInvasive diseaseKi67 expressionSigned-rank testBreast cancerGrade 3Hormone changesPatientsQuantitative immunofluorescenceBC extractSignificant toxicityCancer treatment
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 modelArtificial intelligence applied to breast pathology
Yousif M, van Diest PJ, Laurinavicius A, Rimm D, van der Laak J, Madabhushi A, Schnitt S, Pantanowitz L. Artificial intelligence applied to breast pathology. Virchows Archiv 2021, 480: 191-209. PMID: 34791536, DOI: 10.1007/s00428-021-03213-3.Peer-Reviewed Original ResearchConceptsArtificial intelligenceApplication of AIComplex artificial intelligenceDevelopment of algorithmsComputer visionDeep learningMachine learningMitosis detectionDigital pathologyNeural networkDigital dataHistology imagesTissue segmentationField of pathologyImage analysisIntelligencePromising resultsTaskLearningImagesSegmentationBreast pathologyComputerAlgorithmNetworkDeep 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 standardImmunohistochemistryHematoxylinAlpha-smooth muscle actin expression in the stroma predicts resistance to trastuzumab in patients with early-stage HER2-positive breast cancer
Vathiotis IA, Moutafi MK, Divakar P, Aung TN, Qing T, Fernandez A, Yaghoobi V, El-Abed S, Wang Y, Guillaume S, Nuciforo P, Huober J, Di Cosimo S, Kim SB, Harbeck N, Gomez H, Shafi S, Syrigos KN, Fountzilas G, Sotiriou C, Pusztai L, Warren S, Rimm DL. Alpha-smooth muscle actin expression in the stroma predicts resistance to trastuzumab in patients with early-stage HER2-positive breast cancer. Clinical Cancer Research 2021, 27: 6156-6163. PMID: 34465600, PMCID: PMC8595766, DOI: 10.1158/1078-0432.ccr-21-2103.Peer-Reviewed Original ResearchConceptsDisease-free survivalHER2-positive breast cancerShorter disease-free survivalBreast cancerQuantitative immunofluorescenceEarly-stage HER2-positive breast cancerAlpha-smooth muscle actin expressionAlpha-smooth muscle actinProgesterone receptor statusHigh α-SMA expressionDigital Spatial ProfilerΑ-SMA expressionPromising candidate biomarkerCompanion diagnostic testsMuscle actin expressionDigital spatial profilingCohort validationNeoadjuvant lapatinibAdjuvant trastuzumabReceptor statusClinical trialsUnivariate analysisEstrogen receptorMAIN OUTCOMEΑ-SMAMulti-institutional TSA-amplified Multiplexed Immunofluorescence Reproducibility Evaluation (MITRE) Study
Taube JM, Roman K, Engle EL, Wang C, Ballesteros-Merino C, Jensen SM, McGuire J, Jiang M, Coltharp C, Remeniuk B, Wistuba I, Locke D, Parra ER, Fox BA, Rimm DL, Hoyt C. Multi-institutional TSA-amplified Multiplexed Immunofluorescence Reproducibility Evaluation (MITRE) Study. Journal For ImmunoTherapy Of Cancer 2021, 9: e002197. PMID: 34266881, PMCID: PMC8286792, DOI: 10.1136/jitc-2020-002197.Peer-Reviewed Original ResearchConceptsPD-1/PD-L1 axisPD-L1 axisMultiplexed immunofluorescenceTumor cellsBreast carcinomaNon-small cell lung cancer (NSCLC) tissuesCell lung cancer tissuesCell density assessmentPD-L1 expressionLung cancer tissuesTissue sectionsPercent positive cellsAverage concordanceClinical laboratory processPDL1 expressionMIF assayPD-1PD-L1Predictive biomarkersLow-level expressionPositive cellsCancer tissuesFluorescent detection reagentMultisite trialChromogenic assayAnalysis of multispectral imaging with the AstroPath platform informs efficacy of PD-1 blockade
Berry S, Giraldo NA, Green BF, Cottrell TR, Stein JE, Engle EL, Xu H, Ogurtsova A, Roberts C, Wang D, Nguyen P, Zhu Q, Soto-Diaz S, Loyola J, Sander IB, Wong PF, Jessel S, Doyle J, Signer D, Wilton R, Roskes JS, Eminizer M, Park S, Sunshine JC, Jaffee EM, Baras A, De Marzo AM, Topalian SL, Kluger H, Cope L, Lipson EJ, Danilova L, Anders RA, Rimm DL, Pardoll DM, Szalay AS, Taube JM. Analysis of multispectral imaging with the AstroPath platform informs efficacy of PD-1 blockade. Science 2021, 372 PMID: 34112666, PMCID: PMC8709533, DOI: 10.1126/science.aba2609.Peer-Reviewed Original ResearchMeSH KeywordsAdultAgedAged, 80 and overAntigens, CDAntigens, Differentiation, MyelomonocyticAntineoplastic Agents, ImmunologicalB7-H1 AntigenBiomarkers, TumorCD8 AntigensFemaleFluorescent Antibody TechniqueForkhead Transcription FactorsHumansImmune Checkpoint ProteinsMacrophagesMaleMelanomaMiddle AgedPrognosisProgrammed Cell Death 1 ReceptorProgression-Free SurvivalReceptors, Cell SurfaceSingle-Cell AnalysisSOXE Transcription FactorsT-Lymphocyte SubsetsTreatment OutcomeTumor MicroenvironmentConceptsAnti-programmed cell death 1Anti-PD-1 blockadePD-1 blockadeCell death 1Tissue-based biomarkersLong-term survivalTumor tissue sectionsDeath-1PD-1PD-L1Immunoregulatory moleculesT cellsIndependent cohortMyeloid cellsMelanoma specimensMultiple cell typesTissue sectionsLow/BlockadeCell typesDistinct expression patternsExpression patternsImagingCD8Foxp3An Open Source, Automated Tumor Infiltrating Lymphocyte Algorithm for Prognosis in Triple-Negative Breast Cancer
Bai Y, Cole K, Martinez-Morilla S, Ahmed FS, Zugazagoitia J, Staaf J, Bosch A, Ehinger A, Nimeus E, Hartman J, Acs B, Rimm DL. An Open Source, Automated Tumor Infiltrating Lymphocyte Algorithm for Prognosis in Triple-Negative Breast Cancer. Clinical Cancer Research 2021, 27: clincanres.0325.2021. PMID: 34088723, PMCID: PMC8530841, DOI: 10.1158/1078-0432.ccr-21-0325.Peer-Reviewed Original ResearchBRCA1 Protein Expression Predicts Survival in Glioblastoma Patients from an NRG Oncology RTOG Cohort
Vassilakopoulou M, Won M, Curran WJ, Souhami L, Prados MD, Langer CJ, Rimm DL, Hanna JA, Neumeister VM, Melian E, Diaz AZ, Atkins JN, Komarnicky LT, Schultz CJ, Howard SP, Zhang P, Dicker AP, Knisely JPS. BRCA1 Protein Expression Predicts Survival in Glioblastoma Patients from an NRG Oncology RTOG Cohort. Oncology 2021, 99: 580-588. PMID: 33957633, PMCID: PMC8491475, DOI: 10.1159/000516168.Peer-Reviewed Original ResearchConceptsBRCA1 protein expressionTensin homolog (PTEN) tumor suppressor geneProtein expressionTumor suppressor geneQuantitative protein analysisDNA repairGenetic profiling studiesMolecular markersSuppressor geneProtein analysisProfiling studiesBRCA1 expressionSitu hybridizationExpression levelsTumor formationCommon malignant brain tumorCancer cellsTissue microarrayGlioblastoma tumorsExpressionPre-temozolomide eraGlioblastoma patients