David Klimstra, MD
Louis J.M. Zinterhofer, MD Professor of PathologyCards
About
Research
Publications
2024
Proteomic basis for pancreatic acinar cell carcinoma and pancreatoblastoma as similar yet distinct entities
Tanaka A, Ogawa M, Zhou Y, Hendrickson R, Miele M, Li Z, Klimstra D, Wang J, Roehrl M. Proteomic basis for pancreatic acinar cell carcinoma and pancreatoblastoma as similar yet distinct entities. Npj Precision Oncology 2024, 8: 221. PMID: 39363045, PMCID: PMC11449907, DOI: 10.1038/s41698-024-00708-5.Peer-Reviewed Original ResearchAcinar cell carcinomaPancreatic ductal adenocarcinomaActin-based processesPathway activity differencesCell carcinomaChromosome organizationChromosomal proteinsProteomic basisRNA processingIGF2 pathwayProtein expression patternsEpithelial-to-mesenchymal transitionProteogenomic profilingPancreatic acinar cell carcinomaProteomic landscapeDNA repairCell cycleRare pancreatic malignancyExpression patternsMitochondrial dysfunctionStem cell phenotypeMetabolic adaptationProteinExtracellular matrixPancreatic malignancyA Genomics-Driven Artificial Intelligence-Based Model Classifies Breast Invasive Lobular Carcinoma and Discovers CDH1 Inactivating Mechanisms.
Pareja F, Dopeso H, Wang Y, Gazzo A, Brown D, Banerjee M, Selenica P, Bernhard J, Derakhshan F, da Silva E, Colon-Cartagena L, Basili T, Marra A, Sue J, Ye Q, Da Cruz Paula A, Yeni Yildirim S, Pei X, Safonov A, Green H, Gill K, Zhu Y, Lee M, Godrich R, Casson A, Weigelt B, Riaz N, Wen H, Brogi E, Mandelker D, Hanna M, Kunz J, Rothrock B, Chandarlapaty S, Kanan C, Oakley J, Klimstra D, Fuchs T, Reis-Filho J. A Genomics-Driven Artificial Intelligence-Based Model Classifies Breast Invasive Lobular Carcinoma and Discovers CDH1 Inactivating Mechanisms. Cancer Research 2024, 84: 3478-3489. PMID: 39106449, PMCID: PMC11479818, DOI: 10.1158/0008-5472.can-24-1322.Peer-Reviewed Original ResearchConceptsInvasive lobular carcinomaBiallelic mutationsGenetic alterationsDiagnosing ILCGenotypic-phenotypic correlationsAI modelsBiological discoveryFusion geneCancer diagnosisCDH1Artificial intelligenceWhole-slide imagesInactivation mechanismLobular carcinomaMutationsHistological whole-slide imagesHistopathological featuresValidation cohortHistological featuresBreast neoplasmsHistological ground truthImprove cancer diagnosisSWI/SNF Complex-Deficient Undifferentiated Carcinoma of the Pancreas: Clinicopathologic and Genomic Analysis
Yavas A, Ozcan K, Adsay N, Balci S, Tarcan Z, Hechtman J, Luchini C, Scarpa A, Lawlor R, Mafficini A, Reid M, Xue Y, Yang Z, Haye K, Bellizzi A, Vanoli A, Benhamida J, Balachandran V, Jarnagin W, Park W, O'Reilly E, Klimstra D, Basturk O. SWI/SNF Complex-Deficient Undifferentiated Carcinoma of the Pancreas: Clinicopathologic and Genomic Analysis. Modern Pathology 2024, 37: 100585. PMID: 39094734, PMCID: PMC11585460, DOI: 10.1016/j.modpat.2024.100585.Peer-Reviewed Original ResearchConceptsPancreatic ductal adenocarcinomaUndifferentiated carcinomaConventional pancreatic ductal adenocarcinomaSMARCB1 protein expressionPancreatic undifferentiated carcinomaProtein expressionPD-L1SMARCB1 deletionRhabdoid morphologyPD-L1 protein expressionCase of undifferentiated carcinomaNext-generation sequencingCombined positive scoreLoss of SMARCB1 protein expressionKRAS wild typeNegative prognostic impactChromatin remodeling complex subunitMultiple tumor typesPrognostic impactTumor characteristicsOverall survivalSWI/SNF deficiencyTumor groupGene alterationsInactivating alterationsProteogenomic characterization of pancreatic neuroendocrine tumors uncovers hypoxia and immune signatures in clinically aggressive subtypes
Tanaka A, Ogawa M, Zhou Y, Otani Y, Hendrickson R, Miele M, Li Z, Klimstra D, Wang J, Roehrl M. Proteogenomic characterization of pancreatic neuroendocrine tumors uncovers hypoxia and immune signatures in clinically aggressive subtypes. IScience 2024, 27: 110544. PMID: 39206147, PMCID: PMC11350455, DOI: 10.1016/j.isci.2024.110544.Peer-Reviewed Original ResearchClinically aggressive subtypePancreatic neuroendocrine tumorsProteomic subtypesNeuroendocrine tumorsAggressive subtypeImmune hot tumorsSystemic treatment optionsVariable clinical outcomesTumor grading systemPredicting patient outcomesHot tumorsCytotoxic chemotherapyImmune signaturesImmunosuppressive moleculesImmunotherapy targetClinical aggressivenessSomatostatin analogsRecurrence rateClinical outcomesTreatment optionsEndocrine neoplasmsGlycolysis upregulationPanNETsProteogenomic characterizationInflammatory pathwaysArtificial Intelligence Helps Pathologists Increase Diagnostic Accuracy and Efficiency in the Detection of Breast Cancer Lymph Node Metastases
Retamero J, Gulturk E, Bozkurt A, Liu S, Gorgan M, Moral L, Horton M, Parke A, Malfroid K, Sue J, Rothrock B, Oakley G, DeMuth G, Millar E, Fuchs T, Klimstra D. Artificial Intelligence Helps Pathologists Increase Diagnostic Accuracy and Efficiency in the Detection of Breast Cancer Lymph Node Metastases. The American Journal Of Surgical Pathology 2024, 48: 846-854. PMID: 38809272, PMCID: PMC11191045, DOI: 10.1097/pas.0000000000002248.Peer-Reviewed Original ResearchConceptsLymph node metastasisNode metastasisDetection of lymph node metastasesBreast cancer lymph node metastasisMetastasis detection rateWhole slide imagesBreast cancer stageArtificial intelligenceIncrease diagnostic accuracyReading pathologistsCancer stageDiagnostic accuracyMetastasisCancer metastasisAverage reading timeBreastPathologistsDetection rateAI algorithmsDNA Methylation Profiling Enables Accurate Classification of Nonductal Primary Pancreatic Neoplasms
Verschuur A, Hackeng W, Westerbeke F, Benhamida J, Basturk O, Selenica P, Raicu G, Molenaar I, van Santvoort H, Daamen L, Klimstra D, Yachida S, Luchini C, Singhi A, Geisenberger C, Brosens L. DNA Methylation Profiling Enables Accurate Classification of Nonductal Primary Pancreatic Neoplasms. Clinical Gastroenterology And Hepatology 2024, 22: 1245-1254.e10. PMID: 38382726, DOI: 10.1016/j.cgh.2024.02.007.Peer-Reviewed Original ResearchConceptsPancreatic neoplasmsMachine learning modelsAnalysis of biopsy specimensNonpancreatic neoplasmsNon-pancreatic originDiagnosis of pancreatic neoplasmsPrimary pancreatic neoplasmDiagnostic work-upArea under the curvePre-operative settingLearning modelsMethylation profilesPrimary tumorBiopsy specimensHistopathological diagnosisResected samplesDetecting neoplasmsDNA methylation signaturesTumor typesCancer entitiesLogistic regression modelsNeoplasmsClassifier performanceNeural networkConcordant classificationProteogenomic characterization of primary colorectal cancer and metastatic progression identifies proteome-based subtypes and signatures
Tanaka A, Ogawa M, Zhou Y, Namba K, Hendrickson R, Miele M, Li Z, Klimstra D, Buckley P, Gulcher J, Wang J, Roehrl M. Proteogenomic characterization of primary colorectal cancer and metastatic progression identifies proteome-based subtypes and signatures. Cell Reports 2024, 43: 113810. PMID: 38377004, PMCID: PMC11288375, DOI: 10.1016/j.celrep.2024.113810.Peer-Reviewed Original ResearchConceptsMetastatic colorectal adenocarcinomaModulation of major histocompatibility complexColorectal adenocarcinomaMetastatic progressionEpithelial-to-mesenchymal transition featuresPrimary colorectal adenocarcinomaTumor microenvironment analysisPrimary colorectal cancerCopy number alterationsProgression of colorectal adenocarcinomaAlternative telomere lengtheningTumor suppressor geneOncogenic pathway activationAntigen processing pathwayMajor histocompatibility complexProteomic subtypesLiver metastasesMetastatic lesionsImmune signaturesGenomic alterationsImmune evasionColorectal cancerMicroenvironment analysisSuppressor geneProteogenomic characterization
2023
2328P Alternative molecular mechanisms underpinning breast invasive lobular carcinoma identified by genomics-driven artificial intelligence model
Pareja F, Dopeso H, Wang Y, Gazzo A, Brown D, Selenica P, Bernhard J, Sue J, Lee M, Godrich R, Casson A, Weigelt B, Hanna M, Kunz J, Rothrock B, Kanan C, Oakley G, Klimstra D, Fuchs T, Reis-Filho J. 2328P Alternative molecular mechanisms underpinning breast invasive lobular carcinoma identified by genomics-driven artificial intelligence model. Annals Of Oncology 2023, 34: s1189. DOI: 10.1016/j.annonc.2023.09.1357.Peer-Reviewed Original ResearchClinical Validation of Artificial Intelligence-Augmented Pathology Diagnosis Demonstrates Significant Gains in Diagnostic Accuracy in Prostate Cancer Detection.
Raciti P, Sue J, Retamero J, Ceballos R, Godrich R, Kunz J, Casson A, Thiagarajan D, Ebrahimzadeh Z, Viret J, Lee D, Schüffler P, DeMuth G, Gulturk E, Kanan C, Rothrock B, Reis-Filho J, Klimstra D, Reuter V, Fuchs T. Clinical Validation of Artificial Intelligence-Augmented Pathology Diagnosis Demonstrates Significant Gains in Diagnostic Accuracy in Prostate Cancer Detection. Archives Of Pathology & Laboratory Medicine 2023, 147: 1178-1185. PMID: 36538386, DOI: 10.5858/arpa.2022-0066-oa.Peer-Reviewed Original ResearchConceptsDiagnostic accuracyProstate biopsy specimensProstate cancer detectionProstate cancer diagnosisCancer diagnosisUS Food and Drug Administration authorityWhole slide imagesGenitourinary subspecialistsTumor sizeHistological gradeApplication of artificial intelligenceBiopsy specimensProstateSimulated clinical settingClinical validationAssessment of tissueClinical settingClinical applicationCancerCancer detectionDiagnosisPathologistsDeep learning-based systemDigital whole slide imagesLearning-based systemSolitary Fibrous Tumor of the Pancreas
Yavas A, Tan J, Ozkan H, Yilmaz F, Reid M, Bagci P, Shi J, Shia J, Adsay V, Klimstra D, Basturk O. Solitary Fibrous Tumor of the Pancreas. The American Journal Of Surgical Pathology 2023, 47: 1230-1242. PMID: 37573546, PMCID: PMC10592360, DOI: 10.1097/pas.0000000000002108.Peer-Reviewed Original ResearchConceptsPancreatic solitary fibrous tumorSolitary fibrous tumorNuclear STAT6 expressionFibrous tumorTumor cellsDifferential diagnosis of mesenchymal neoplasmsSTAT6 expressionAtypical spindle cell tumorDiagnosis of mesenchymal neoplasmsLow-grade stromal tumorsMetastatic renal cell carcinomaSpindle tumor cellsFree of diseaseLow-grade sarcomaSpindle cell tumorsRenal cell carcinomaNAB2-STAT6 fusionFollow-up dataStromal tumorsHypervascular massNeuroendocrine tumorsCell carcinomaMesenchymal neoplasmsCell tumorsCystic areas