2018
Nuclear shape and orientation features from H&E images predict survival in early-stage estrogen receptor-positive breast cancers
Lu C, Romo-Bucheli D, Wang X, Janowczyk A, Ganesan S, Gilmore H, Rimm D, Madabhushi A. Nuclear shape and orientation features from H&E images predict survival in early-stage estrogen receptor-positive breast cancers. Laboratory Investigation 2018, 98: 1438-1448. PMID: 29959421, PMCID: PMC6214731, DOI: 10.1038/s41374-018-0095-7.Peer-Reviewed Original ResearchMeSH KeywordsAdultAgedBreast NeoplasmsCarcinoma, Ductal, BreastCell Nucleus ShapeConnecticutEosine Yellowish-(YS)FemaleHematoxylinHumansMachine LearningMiddle AgedRetrospective StudiesConceptsEarly-stage estrogen receptor-positive breast cancerEstrogen receptor-positive breast cancerReceptor-positive breast cancerBreast cancerRank sum testHazard ratioHistomorphometric featuresShort-term overall survivalLymph node negativeTissue microarray cohortPoor survival outcomesUnivariate survival analysisWilcoxon rank sum testAdjuvant chemotherapyMicroarray cohortOverall survivalNode negativeT stageHistology gradePatient survivalSurvival outcomesPathological parametersNuclear gradeOutcome groupPoor survivalMacrodissection prior to closed system RT-qPCR is not necessary for estrogen receptor and HER2 concordance with IHC/FISH in breast cancer
Gupta S, Mani NR, Carvajal-Hausdorf DE, Bossuyt V, Ho K, Weidler J, Wong W, Rhees B, Bates M, Rimm DL. Macrodissection prior to closed system RT-qPCR is not necessary for estrogen receptor and HER2 concordance with IHC/FISH in breast cancer. Laboratory Investigation 2018, 98: 1076-1083. PMID: 29858579, PMCID: PMC6119113, DOI: 10.1038/s41374-018-0064-1.Peer-Reviewed Original ResearchMeSH KeywordsBiomarkers, TumorBreast NeoplasmsCarcinoma, Ductal, BreastCarcinoma, Intraductal, NoninfiltratingFemaleGene Expression Regulation, NeoplasticHumansImmunohistochemistryIn Situ Hybridization, FluorescenceParaffin EmbeddingPathology, ClinicalReal-Time Polymerase Chain ReactionReceptor, ErbB-2Receptors, EstrogenReproducibility of ResultsSensitivity and SpecificityTissue FixationConceptsIHC/FISHDCIS cohortRT-qPCRMRNA transcript levelsDuctal carcinoma casesFine needle aspiratesMRNA expression levelsHER2 concordanceER positivityDuctal carcinomaHER2 expressionGeneXpert systemCarcinoma casesInvasive tumorsNeedle biopsyBreast cancerEstrogen receptorClinical ImmunohistochemistryBiopsy areaTumor tissueMRNA expressionTumor areaCohortMRNA levelsMRNA markers
2012
Delay to formalin fixation ‘cold ischemia time': effect on ERBB2 detection by in-situ hybridization and immunohistochemistry
Portier BP, Wang Z, Downs-Kelly E, Rowe JJ, Patil D, Lanigan C, Budd GT, Hicks DG, Rimm DL, Tubbs RR. Delay to formalin fixation ‘cold ischemia time': effect on ERBB2 detection by in-situ hybridization and immunohistochemistry. Modern Pathology 2012, 26: 1-9. PMID: 22899285, DOI: 10.1038/modpathol.2012.123.Peer-Reviewed Original Research
2011
Standardization of Estrogen Receptor Measurement in Breast Cancer Suggests False-Negative Results Are a Function of Threshold Intensity Rather Than Percentage of Positive Cells
Welsh AW, Moeder CB, Kumar S, Gershkovich P, Alarid ET, Harigopal M, Haffty BG, Rimm DL. Standardization of Estrogen Receptor Measurement in Breast Cancer Suggests False-Negative Results Are a Function of Threshold Intensity Rather Than Percentage of Positive Cells. Journal Of Clinical Oncology 2011, 29: 2978-2984. PMID: 21709197, PMCID: PMC3157961, DOI: 10.1200/jco.2010.32.9706.Peer-Reviewed Original ResearchConceptsER-positive patientsEstrogen receptorQuantitative immunofluorescenceBreast cancerTissue microarrayPositive cellsIndependent retrospective cohortsEstrogen receptor measurementsAssessment of survivalTMA cohortFalse-negative resultsRetrospective cohortER immunoreactivityTest discordancePrognostic outcomesIndependent cohortReceptor measurementsLimitations of immunohistochemistryPatientsDiscrepant casesCohortIHC methodPathologists' judgmentsDiscrepant resultsStandardized assaysLoss 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 studyQuantitative assessment shows loss of antigenic epitopes as a function of pre-analytic variables
Bai Y, Tolles J, Cheng H, Siddiqui S, Gopinath A, Pectasides E, Camp RL, Rimm DL, Molinaro AM. Quantitative assessment shows loss of antigenic epitopes as a function of pre-analytic variables. Laboratory Investigation 2011, 91: 1253-1261. PMID: 21519325, PMCID: PMC3145004, DOI: 10.1038/labinvest.2011.75.Peer-Reviewed Original ResearchMeSH KeywordsAdultAgedAged, 80 and overBiomarkersBiopsy, NeedleBreast NeoplasmsCarcinoma, Ductal, BreastCold IschemiaEpitopesFemaleHumansImmunohistochemistryMiddle AgedSpecimen HandlingConceptsCore needle biopsyCold ischemic timePre-analytic variablesNeedle biopsyEstrogen receptorIschemic timeTumor resectionTumor resection specimensAntigenic lossResection specimensTissue biomarkersTotal AktBiopsyPhospho-AktQuantitative immunofluorescencePhospho-ERKPhospho-S6K1Antigenic epitopesTotal ERKResectionTotal proteinCytokeratinImmunological methodsAntigenicitySignificant changes
2009
Growth factor receptor-bound protein-7 (Grb7) as a prognostic marker and therapeutic target in breast cancer
Nadler Y, González AM, Camp RL, Rimm DL, Kluger HM, Kluger Y. Growth factor receptor-bound protein-7 (Grb7) as a prognostic marker and therapeutic target in breast cancer. Annals Of Oncology 2009, 21: 466-473. PMID: 19717535, PMCID: PMC2826097, DOI: 10.1093/annonc/mdp346.Peer-Reviewed Original ResearchMeSH KeywordsAdultAgedAged, 80 and overBiomarkers, TumorBlotting, WesternBreast NeoplasmsCarcinoma, Ductal, BreastCarcinoma, LobularFemaleFluorescent Antibody TechniqueFollow-Up StudiesGRB7 Adaptor ProteinHumansImage Processing, Computer-AssistedMiddle AgedPrognosisReceptor, ErbB-2Survival RateTissue Array AnalysisTumor Cells, CulturedYoung AdultConceptsHER2/neuBreast cancerPrognostic markerHER2/neu-positive breast cancerGRB7 expressionHigh HER2/neuNeu-positive breast cancerHER2/neu overexpressionPrimary breast cancerBreast cancer patientsIndependent prognostic markerNode-positive subsetValuable prognostic markerProtein 7Cy5-conjugated antibodiesMultivariable analysisWorse prognosisEntire cohortCancer patientsNeu overexpressionTissue microarrayTherapeutic targetCancerNeuPatients
2008
High levels of vascular endothelial growth factor and its receptors (VEGFR-1, VEGFR-2, neuropilin-1) are associated with worse outcome in breast cancer
Ghosh S, Sullivan CA, Zerkowski MP, Molinaro AM, Rimm DL, Camp RL, Chung GG. High levels of vascular endothelial growth factor and its receptors (VEGFR-1, VEGFR-2, neuropilin-1) are associated with worse outcome in breast cancer. Human Pathology 2008, 39: 1835-1843. PMID: 18715621, PMCID: PMC2632946, DOI: 10.1016/j.humpath.2008.06.004.Peer-Reviewed Original ResearchMeSH KeywordsAdultAgedAged, 80 and overBiomarkers, TumorBreast NeoplasmsCarcinoma, Ductal, BreastCarcinoma, LobularConnecticutFemaleFluorescent Antibody Technique, IndirectHumansImage Processing, Computer-AssistedImmunoenzyme TechniquesKaplan-Meier EstimateMiddle AgedNeuropilin-1Receptors, Vascular Endothelial Growth FactorSurvival RateTissue Array AnalysisVascular Endothelial Growth Factor AVascular Endothelial Growth Factor Receptor-1Vascular Endothelial Growth Factor Receptor-2Young AdultConceptsVascular endothelial growth factorEndothelial growth factorBreast cancerVEGFR-1Growth factorNeuropilin-1VEGFR-2Kaplan-Meier survival analysisBreast cancer tissue microarrayVascular endothelial growth factor receptorPrimary breast cancerStandard prognostic factorsEndothelial growth factor receptorPrimary breast adenocarcinomaCancer tissue microarrayTumor-specific expressionGrowth factor receptorPrognostic factorsPrognostic significancePrognostic valueWorse outcomesLarge cohortTissue microarraySurvival analysisSignificant association
2005
Automated Quantitative Analysis of E-Cadherin Expression in Lymph Node Metastases Is Predictive of Survival in Invasive Ductal Breast Cancer
Harigopal M, Berger AJ, Camp RL, Rimm DL, Kluger HM. Automated Quantitative Analysis of E-Cadherin Expression in Lymph Node Metastases Is Predictive of Survival in Invasive Ductal Breast Cancer. Clinical Cancer Research 2005, 11: 4083-4089. PMID: 15930343, DOI: 10.1158/1078-0432.ccr-04-2191.Peer-Reviewed Original ResearchConceptsE-cadherin expressionLymph node metastasisNodal metastasisBreast cancerImproved survivalNode metastasisTissue microarrayNode-positive breast cancerInvasive ductal breast cancerHER2/neu statusAnti-invasive roleInvasive ductal tumorsNode-positive patientsDuctal breast cancerSubset of patientsGood prognostic markerAggressive tumor behaviorStrong E-cadherin expressionHigh E-cadherin expressionCy5-conjugated antibodiesDuctal tumorsMetastatic sitesPrognostic valueTumor sizePrimary tumor
2002
Quantitative examination of mechanophysical tumor cell enrichment in fine‐needle aspiration specimens
Ernst LM, Rimm DL. Quantitative examination of mechanophysical tumor cell enrichment in fine‐needle aspiration specimens. Cancer 2002, 96: 275-279. PMID: 12378594, DOI: 10.1002/cncr.10746.Peer-Reviewed Original ResearchConceptsFine-needle aspirationBreast carcinomaMalignant cellsSurgical excisionHistologic sectionsDiagnostic fine needle aspirationNontumor cellsSurgical excision specimensChi-square testTumor cell enrichmentExcision specimensFNA specimensCurrent studyFNA specimenCarcinomaCDNA microarrayRepresentative slidesNonmalignant cellsThinPrep preparationsTotal cellsTissue sectionsCell enrichmentTumorsExcisionCellsp53 Mutations as Tumor Markers in Fine Needle Aspirates of Palpable Breast Masses
Dillon DA, Hipolito E, Zheng K, Rimm DL, Costa JC. p53 Mutations as Tumor Markers in Fine Needle Aspirates of Palpable Breast Masses. Acta Cytologica 2002, 46: 841-847. PMID: 12365217, DOI: 10.1159/000327057.Peer-Reviewed Original ResearchMeSH KeywordsAbscessAdenocarcinomaAdultAgedAged, 80 and overAmino Acid SubstitutionBiomarkers, TumorBiopsy, NeedleBreast NeoplasmsCarcinoma, Ductal, BreastCodon, TerminatorCystsDNA Mutational AnalysisDNA, NeoplasmExonsFemaleFrameshift MutationGenes, p53GenotypeHumansMiddle AgedMutationPolymorphism, Single-Stranded ConformationalRetrospective StudiesConceptsFine needle aspiratesP53 exons 5Breast massesPolymerase chain reactionNeedle aspiratesP53 mutationsSingle-strand conformational polymorphism analysisSubsequent excisional biopsyPalpable breast massesPotential diagnostic utilityDefinitive cytologic diagnosisTumor cell markersExon 5Molecular diagnostic markersExcisional biopsyBenign cytologyBreast carcinomaSuspicious cytologyRetrospective analysisCytologic diagnosisTumor markersDiagnostic criteriaBiopsy tissueMorphologic diagnosisDiagnostic utility
1998
Expression of c‐met is a strong independent prognostic factor in breast carcinoma
Ghoussoub R, Dillon D, D'Aquila T, Rimm E, Fearon E, Rimm D. Expression of c‐met is a strong independent prognostic factor in breast carcinoma. Cancer 1998, 82: 1513-1520. PMID: 9554529, DOI: 10.1002/(sici)1097-0142(19980415)82:8<1513::aid-cncr13>3.0.co;2-7.Peer-Reviewed Original ResearchConceptsBreast carcinomaIndependent predictorsStrong independent prognostic factorCox proportional hazards modelGrowth factorIndependent prognostic factorLymph node statusSubset of patientsInvasive ductal carcinomaUseful prognostic markerProportional hazards modelBreast tumor specimensHepatocyte growth factorNegative patientsPrognostic factorsAggressive diseaseDuctal carcinomaNode statusPrognostic valuePrognostic markerTumor specimensHazards modelPatientsPredictive valueSurvival rateThe expression of p120ctn protein in breast cancer is independent of alpha- and beta-catenin and E-cadherin.
Dillon DA, D'Aquila T, Reynolds AB, Fearon ER, Rimm DL. The expression of p120ctn protein in breast cancer is independent of alpha- and beta-catenin and E-cadherin. American Journal Of Pathology 1998, 152: 75-82. PMID: 9422525, PMCID: PMC1858125.Peer-Reviewed Original Research
1997
Localization and quantitation of expression of the cell motility-related protein thymosin beta15 in human breast tissue.
Gold JS, Bao L, Ghoussoub RA, Zetter BR, Rimm DL. Localization and quantitation of expression of the cell motility-related protein thymosin beta15 in human breast tissue. Modern Pathology 1997, 10: 1106-12. PMID: 9388061.Peer-Reviewed Original ResearchConceptsBreast cancerBreast tissueNonmetastatic breast cancerUseful prognostic markerPotential early markerMalignant breast tissueProstate cell linesThymosin beta15Human breast tissuePrognostic valueDuctal carcinomaPrognostic markerBreast malignancyAffinity-purified polyclonal antibodiesBreast epitheliumEarly markerCancerAdditional studiesProtein levelsProstate modelCell linesPrecise rolePolyclonal antibodiesMarkersTissue