Featured Publications
Tissue Age Affects Antigenicity and Scoring for the 22C3 Immunohistochemistry Companion Diagnostic Test
Fernandez A, Gaule P, Rimm D. Tissue Age Affects Antigenicity and Scoring for the 22C3 Immunohistochemistry Companion Diagnostic Test. Modern Pathology 2023, 36: 100159. PMID: 36925070, PMCID: PMC10502188, DOI: 10.1016/j.modpat.2023.100159.Peer-Reviewed Original ResearchMeSH KeywordsB7-H1 AntigenBiomarkers, TumorCarcinoma, Non-Small-Cell LungDiagnostic Tests, RoutineEpitopesHumansImmunohistochemistryLung NeoplasmsConceptsPD-L1 signalTumor proportion scoreTissue microarray cohortCell lung cancerPrevious clinical diagnosisWhole tissue sectionsCompanion diagnostic testsMultiple cancer typesMicroarray cohortTMA cohortLaboratory-developed testsPD-L1NSCLC casesLung cancerProportion scorePositive stainingAntibody 22C3Immunohistochemistry testsClinical diagnosisExtracellular domainCancer typesDiagnostic testsArchival tissueDomain antigenAntibodies
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 benefitsPatientsCD68Digital spatial proteomic profiling reveals immune checkpoints as biomarkers in lymphoid aggregates and tumor microenvironment of desmoplastic melanoma
Su D, Schoenfeld D, Ibrahim W, Cabrejo R, Djureinovic D, Baumann R, Rimm D, Khan S, Halaban R, Kluger H, Olino K, Galan A, Clune J. Digital spatial proteomic profiling reveals immune checkpoints as biomarkers in lymphoid aggregates and tumor microenvironment of desmoplastic melanoma. Journal For ImmunoTherapy Of Cancer 2024, 12: e008646. PMID: 38519058, PMCID: PMC10961546, DOI: 10.1136/jitc-2023-008646.Peer-Reviewed Original ResearchMeSH KeywordsActinsBiomarkers, TumorCTLA-4 AntigenHumansMelanomaProgrammed Cell Death 1 ReceptorProteomicsTumor MicroenvironmentConceptsCTLA-4 expression levelsCancer-associated fibroblastsAssociated with worse survivalExpression of immune checkpointsLAG-3 expressionDesmoplastic melanomaLymphoid aggregatesCTLA-4PD-1Immune checkpointsIntratumoral leukocytesLAG-3Tumor compartmentsWorse survivalCD20+B cellsIncreased expression of immune checkpointsProgrammed cell death protein 1Macrophage/monocyte markerSentinel lymph node positivityCell death protein 1Associated with poor prognosisLymph node positivityDense fibrous stromaPotential prognostic significanceCore of tumors
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 studiesMultiplex Immunohistochemistry and Immunofluorescence: A Practical Update for Pathologists
Harms P, Frankel T, Moutafi M, Rao A, Rimm D, Taube J, Thomas D, Chan M, Pantanowitz L. Multiplex Immunohistochemistry and Immunofluorescence: A Practical Update for Pathologists. Modern Pathology 2023, 36: 100197. PMID: 37105494, DOI: 10.1016/j.modpat.2023.100197.Peer-Reviewed Original ResearchConceptsDigital spatial profilingMost clinical laboratoriesTumor microenvironmentImmunofluorescence/immunohistochemistryImmuno-oncology researchDiagnostic practiceClinical laboratoriesRoutine diagnostic useAntitumor immunityAdvanced cancerImmune populationsMultiplex stainingEosin stainingIHC stainsPractical updateClinical diagnostic practiceMultiplex immunohistochemistrySingle biomarkerImmunohistochemistryMultiplexed immunohistochemistryStandardized protocolChromogenic immunohistochemistryDiagnostic useMultiple biomarkersSerial sectionsMulti-Institutional Study of Pathologist Reading of the Programmed Cell Death Ligand-1 Combined Positive Score Immunohistochemistry Assay for Gastric or Gastroesophageal Junction Cancer
Fernandez A, Robbins C, Gaule P, Agostini-Vulaj D, Anders R, Bellizzi A, Chen W, Chen Z, Gopal P, Zhao L, Lisovsky M, Liu X, Shia J, Wang H, Yang Z, McCann L, Chan Y, Weidler J, Bates M, Zhang X, Rimm D. Multi-Institutional Study of Pathologist Reading of the Programmed Cell Death Ligand-1 Combined Positive Score Immunohistochemistry Assay for Gastric or Gastroesophageal Junction Cancer. Modern Pathology 2023, 36: 100128. PMID: 36889057, PMCID: PMC10198879, DOI: 10.1016/j.modpat.2023.100128.Peer-Reviewed Original ResearchConceptsOverall percent agreementCut pointsReal-world settingHigher cut pointsCell death ligand 1Percent agreementGastroesophageal junction cancerPD-L1 immunohistochemistryDeath ligand 1Companion diagnostic testsMessenger RNA measurementsJunction cancerCancer casesImmunohistochemistry assaysIHC resultsDrug AdministrationPredictive valueScoring systemRange of assaysDiagnostic testsInstitutional studyRNA measurementsImmunohistochemistryPoor specificityPathologist's readingAn Algorithm as a Biomarker for Response to Immune Checkpoint Inhibitor Therapy
Rimm D. An Algorithm as a Biomarker for Response to Immune Checkpoint Inhibitor Therapy. JAMA Oncology 2023, 9: 60-61. PMID: 36394848, DOI: 10.1001/jamaoncol.2022.4772.Peer-Reviewed Original ResearchMulti-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
Proceedings From the ASCO/College of American Pathologists Immune Checkpoint Inhibitor Predictive Biomarker Summit.
Hayes D, Herbst R, Myles J, Topalian S, Yohe S, Aronson N, Bellizzi A, Basu Roy U, Bradshaw G, Edwards R, El-Gabry E, Elvin J, Gajewski T, McShane L, Oberley M, Philip R, Rimm D, Rosenbaum J, Rubin E, Schlager L, Sherwood S, Stewart M, Taube J, Thurin M, Vasalos P, Laser J. Proceedings From the ASCO/College of American Pathologists Immune Checkpoint Inhibitor Predictive Biomarker Summit. JCO Precision Oncology 2022, 6: e2200454. PMID: 36446042, PMCID: PMC10530621, DOI: 10.1200/po.22.00454.Peer-Reviewed Original ResearchMeSH KeywordsAgedBiomarkers, TumorHumansImmune Checkpoint InhibitorsMedicareMicrosatellite InstabilityNeoplasmsPathologistsUnited StatesConceptsICI therapyImmune checkpoint inhibition therapyDeath ligand 1 (PD-L1) expressionMultiple predictive biomarkersTumor biomarker testsCheckpoint inhibition therapyLigand 1 expressionDeath ligand 1Field of oncologyICI benefitPredictive factorsPredictive biomarkersInhibition therapyNeoantigen expressionBiomarker testsHealth insurance organizationsUS FoodDrug AdministrationAmerican PathologistsMedicaid ServicesTherapyBiomarker developmentNational InstituteLigand 1Clinical applicationPredictive 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 cycle
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 modelQuantitative assessment of the immune microenvironment in African American Triple Negative Breast Cancer: a case–control study
Yaghoobi V, Moutafi M, Aung TN, Pelekanou V, Yaghoubi S, Blenman K, Ibrahim E, Vathiotis IA, Shafi S, Sharma A, O’Meara T, Fernandez AI, Pusztai L, Rimm DL. Quantitative assessment of the immune microenvironment in African American Triple Negative Breast Cancer: a case–control study. Breast Cancer Research 2021, 23: 113. PMID: 34906209, PMCID: PMC8670126, DOI: 10.1186/s13058-021-01493-w.Peer-Reviewed Original ResearchMeSH KeywordsBiomarkers, TumorBlack or African AmericanCase-Control StudiesHumansTriple Negative Breast NeoplasmsTumor MicroenvironmentConceptsNegative breast cancerT cellsTumor microenvironmentAA patientsImmune cellsAA tumorsBreast cancerPurposeTriple-negative breast cancerAfrican AmericansTriple-negative breast cancerCase-control studySignificant differencesActivated T cellsImmunologic biomarkersPD-L1Lymphocytic infiltrationLymphoid infiltrationImmune microenvironmentControl cohortTNBC tumorsMyeloid markersQuantitative immunofluorescenceMean expression levelPatientsTNBCStandardization of PD-L1 immunohistochemistry
Martinez-Morilla S, Moutafi M, Rimm DL. Standardization of PD-L1 immunohistochemistry. Modern Pathology 2021, 35: 294-295. PMID: 34508229, PMCID: PMC8860739, DOI: 10.1038/s41379-021-00917-4.Peer-Reviewed Original ResearchMulti-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 ResearchMeSH KeywordsBiomarkers, TumorFemaleFluorescent Antibody TechniqueHumansImmunohistochemistryLaboratories, ClinicalMaleTissue Array AnalysisConceptsPD-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 assayTargeting Pyruvate Kinase M2 Phosphorylation Reverses Aggressive Cancer Phenotypes
Apostolidi M, Vathiotis IA, Muthusamy V, Gaule P, Gassaway BM, Rimm DL, Rinehart J. Targeting Pyruvate Kinase M2 Phosphorylation Reverses Aggressive Cancer Phenotypes. Cancer Research 2021, 81: 4346-4359. PMID: 34185676, PMCID: PMC8373815, DOI: 10.1158/0008-5472.can-20-4190.Peer-Reviewed Original ResearchMeSH KeywordsActive Transport, Cell NucleusAnimalsBiomarkers, TumorCarrier ProteinsCell Line, TumorCollagenCyclic N-OxidesDrug CombinationsGenome, HumanHumansIndolizinesLamininMCF-7 CellsMembrane ProteinsMiceNeoplasm InvasivenessNeoplasm TransplantationNeoplasmsOxidation-ReductionPhenotypePhosphorylationProtein IsoformsProteoglycansProteomicsPyridazinesPyridinium CompoundsPyrrolesPyruvate KinaseThyroid HormonesTriple Negative Breast NeoplasmsConceptsTriple-negative breast cancerPyruvate kinase M2TEPP-46Breast cancerAggressive breast cancer cell phenotypesCharacteristic nuclear staining patternAggressive breast cancer subtypeAggressive breast cancer phenotypeBreast cancer cell phenotypeCDK inhibitor dinaciclibCombination of dinaciclibLack of biomarkersEffective therapeutic approachBreast cancer phenotypeBreast cancer subtypesCancer phenotypePhosphorylation of PKM2Cyclin-dependent kinase (CDK) pathwayMouse xenograft modelAggressive cancer phenotypeNuclear staining patternLower survival rateImpaired redox balancePrognostic valueCancer cell phenotypeAnalysis 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 patternsImagingCD8Foxp3BRCA1 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 patientsComparison of programmed death-ligand 1 protein expression between primary and metastatic lesions in patients with lung cancer
Moutafi MK, Tao W, Huang R, Haberberger J, Alexander B, Ramkissoon S, Ross JS, Syrigos K, Wei W, Pusztai L, Rimm DL, Vathiotis IA. Comparison of programmed death-ligand 1 protein expression between primary and metastatic lesions in patients with lung cancer. Journal For ImmunoTherapy Of Cancer 2021, 9: e002230. PMID: 33833050, PMCID: PMC8039214, DOI: 10.1136/jitc-2020-002230.Peer-Reviewed Original ResearchConceptsPD-L1 expressionMetastatic lesionsLung cancer casesLung cancerCancer casesAdvanced stage non-small cell lung cancerNon-small cell lung cancerNon-squamous histologyCell lung cancerFuture patient managementDefinite diagnostic testSquamous histologyFoundation MedicineLymph nodesRoutine careHistologic subtypeMetastatic sitesPrimary lesionRetrospective studyAdrenal glandPrimary tumorPleural fluidPatient managementTrial designDrug AdministrationPD-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 assaysA new tool for technical standardization of the Ki67 immunohistochemical assay
Aung TN, Acs B, Warrell J, Bai Y, Gaule P, Martinez-Morilla S, Vathiotis I, Shafi S, Moutafi M, Gerstein M, Freiberg B, Fulton R, Rimm DL. A new tool for technical standardization of the Ki67 immunohistochemical assay. Modern Pathology 2021, 34: 1261-1270. PMID: 33536573, PMCID: PMC8222064, DOI: 10.1038/s41379-021-00745-6.Peer-Reviewed Original Research