2023
Pathological response in mucinous carcinoma of breast after neoadjuvant therapy - a multi-institutional study
Zhan H, Fineberg S, Podany P, Zeng J, Wang Y, Harigopal M, Singh K. Pathological response in mucinous carcinoma of breast after neoadjuvant therapy - a multi-institutional study. Human Pathology 2023, 142: 15-19. PMID: 37972873, DOI: 10.1016/j.humpath.2023.10.002.Peer-Reviewed Original ResearchConceptsNeoadjuvant endocrine therapyResidual tumour cellularityNeoadjuvant chemotherapyNeoadjuvant therapyMucinous carcinomaPathologic responseEndocrine therapyPathological responseMucin poolsBreast cancerEstrogen receptorTumor cellularityAcellular mucin poolsFavorable histologic subtypePreoperative adjuvant therapyRetrospective cohort studyComplete pathologic responseInvasive breast cancerNET groupMulti-institutional studyNeoadjuvant HER2Adjuvant therapyMC patientsCohort studyPathologic reviewThe correlation of ESR1 genetic aberrations with estrogen receptor and progesterone receptor status in metastatic and primary estrogen receptor-positive breast carcinomas
Moreira-Dinzey J, Zhan H, Rozenblit M, Krishnamurti U, Harigopal M, Zhong M, Liang Y. The correlation of ESR1 genetic aberrations with estrogen receptor and progesterone receptor status in metastatic and primary estrogen receptor-positive breast carcinomas. Human Pathology 2023, 137: 56-62. PMID: 37127079, DOI: 10.1016/j.humpath.2023.04.017.Peer-Reviewed Original ResearchMeSH KeywordsBiomarkers, TumorBreast NeoplasmsEstrogen Receptor alphaFemaleHumansReceptors, EstrogenReceptors, ProgesteroneConceptsMetastatic tumorsBreast carcinomaGenetic aberrationsPR statusPrimary tumorBreast cancerControl groupER/PR statusEstrogen receptor-positive breast carcinomasER-positive breast cancerER positivity rateMetastatic breast cancerProgesterone receptor statusMetastatic breast carcinomaMore liver metastasesPrimary breast carcinomaWild-type groupEstrogen receptor 1 geneReceptor 1 geneWild-type controlsLiver metastasesReceptor statusClinicopathological featuresER expressionControl tumorsMulti-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
AMACR Expression is a Potential Diagnostic Marker in Apocrine Lesions of Breast, and is Associated with High Histologic Grade and Lymph Node Metastases in Some Invasive Apocrine Breast Cancers
Lerner G, Tang H, Singh K, Golestani R, St Claire S, Humphrey P, Lannin D, Janostiak R, Harigopal M. AMACR Expression is a Potential Diagnostic Marker in Apocrine Lesions of Breast, and is Associated with High Histologic Grade and Lymph Node Metastases in Some Invasive Apocrine Breast Cancers. Clinical Breast Cancer 2022, 23: 199-210. PMID: 36577560, DOI: 10.1016/j.clbc.2022.11.012.Peer-Reviewed Original ResearchConceptsInvasive ductal carcinomaTriple-negative breast cancerHigh histologic gradeApocrine differentiationAMACR expressionEstrogen receptorApocrine DCISER-/PRHistologic gradeProgesterone receptorApocrine featuresBreast cancerHuman epidermal growth factor 2 (HER2) statusLack of ERDistant metastasis-free survivalDiagnostic markerInitial N stageLack estrogen receptorApocrine breast cancerLymph node metastasisNegative breast cancerAndrogen receptor mRNACoA racemase expressionBenign breast tissueBreast cancer cohortPD-L1 protein expression in relation to recurrence score values in early-stage ER + breast cancer
Rozenblit M, Blenman K, Harigopal M, Reisenbichler E, Singh K, Qing T, Ibrahim E, Ramkissoon S, Asmelash S, Lin HK, Roberts M, Ross J, Huang RSP, Pusztai L. PD-L1 protein expression in relation to recurrence score values in early-stage ER + breast cancer. Breast Cancer Research And Treatment 2022, 196: 221-227. PMID: 36028784, DOI: 10.1007/s10549-022-06712-2.Peer-Reviewed Original ResearchMeSH KeywordsB7-H1 AntigenBiomarkers, TumorBreast NeoplasmsFemaleHumansLymphocyte CountLymphocytes, Tumor-InfiltratingPrognosisConceptsPD-L1 positivityPD-L1 protein expressionPD-L1 expressionGrade 3 cancersPD-L1TIL scoreTumor gradeMultivariate analysisHigher PD-L1 positivityTumor-infiltrating lymphocyte countsConclusionPD-L1 expressionProtein expressionPD-L1 immunohistochemistryChi-square testResultsPD-L1T1 cancersLymphocyte countT3 tumorsIndependent predictorsTumor sizeLarge tumorsPositivity rateCell positivityBreast cancerGrade 2Increased Expression of LEF1 and β-Catenin in Invasive Micropapillary Carcinoma of the Breast is Associated With Lymphovascular Invasion and Lymph Node Metastasis
Dolezal D, Zhang X, Harigopal M. Increased Expression of LEF1 and β-Catenin in Invasive Micropapillary Carcinoma of the Breast is Associated With Lymphovascular Invasion and Lymph Node Metastasis. Applied Immunohistochemistry & Molecular Morphology 2022, 30: 557-565. PMID: 35960138, DOI: 10.1097/pai.0000000000001052.Peer-Reviewed Original ResearchConceptsInvasive micropapillary breast carcinomaLymph node metastasisLymphoid enhancer-binding factor 1Lymphovascular invasionNode metastasisNodal metastasisPrimary tumorΒ-cateninBreast tumorsRare breast cancer subtypeSmall tumor cell clustersLEF1 expressionMicropapillary breast carcinomaAggressive breast tumorsBasal-like carcinomasInvasive micropapillary carcinomaΒ-catenin expression levelsBreast cancer subtypesΒ-catenin expressionTumor cell clustersEnhancer-binding factor 1Disease relapseMicropapillary carcinomaBreast carcinomaHigh incidenceEvaluation of TRPS1 Expression in Pleural Effusion Cytology Specimens With Metastatic Breast Carcinoma
Wang M, Stendahl K, Cai G, Adeniran A, Harigopal M, Gilani SM. Evaluation of TRPS1 Expression in Pleural Effusion Cytology Specimens With Metastatic Breast Carcinoma. American Journal Of Clinical Pathology 2022, 158: 416-425. PMID: 35760555, DOI: 10.1093/ajcp/aqac066.Peer-Reviewed Original ResearchConceptsTrichorhinophalangeal syndrome type 1Breast originMetastatic carcinomaTRPS1 expressionBreast primaryBreast carcinomaPrimary siteMC casesMetastatic breast carcinomaSquamous cell carcinomaPleural effusion cytologySyndrome type 1Cell block materialStrong nuclear expressionEffusion cytology specimensCell carcinomaUrothelial carcinomaIHC panelMalignant melanomaLung adenocarcinomaIHC stainingPositive stainingCytology specimensCarcinomaEffusion cytologyExamination 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 ResearchMeSH KeywordsBreastBreast NeoplasmsFemaleHumansImmunohistochemistryIn Situ Hybridization, FluorescenceReceptor, ErbB-2ConceptsBreast 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 expressionBiopsyIHCConcordanceConcordance in Breast Cancer Grading by Artificial Intelligence on Whole Slide Images Compares With a Multi-Institutional Cohort of Breast Pathologists.
Mantrala S, Ginter PS, Mitkari A, Joshi S, Prabhala H, Ramachandra V, Kini L, Idress R, D'Alfonso TM, Fineberg S, Jaffer S, Sattar AK, Chagpar AB, Wilson P, Singh K, Harigopal M, Koka D. Concordance in Breast Cancer Grading by Artificial Intelligence on Whole Slide Images Compares With a Multi-Institutional Cohort of Breast Pathologists. Archives Of Pathology & Laboratory Medicine 2022, 146: 1369-1377. PMID: 35271701, DOI: 10.5858/arpa.2021-0299-oa.Peer-Reviewed Original ResearchMeSH KeywordsArtificial IntelligenceBreast NeoplasmsFemaleHumansObserver VariationPathologistsReproducibility of ResultsConceptsWhole slide imagingArtificial intelligenceNottingham grading systemDigital whole slide imagingVirtual microscopyBreast cancer gradingWhole slide imagesDeep learningAI methodologiesExplainable methodsDigital pathologySlide imagesCancer gradingMulti-institutional groupIntelligenceLearningImagesImportant criteriaFrameworkAdvent
2021
EZH2 Protein Expression in Triple-negative Breast Cancer Treated With Neoadjuvant Chemotherapy: An Exploratory Study of Association With Tumor Response and Prognosis
Fineberg S, Tian X, Makower D, Harigopal M, Lo Y. EZH2 Protein Expression in Triple-negative Breast Cancer Treated With Neoadjuvant Chemotherapy: An Exploratory Study of Association With Tumor Response and Prognosis. Applied Immunohistochemistry & Molecular Morphology 2021, 30: 157-164. PMID: 35262520, DOI: 10.1097/pai.0000000000000998.Peer-Reviewed Original ResearchConceptsTriple-negative breast cancerResidual cancer burdenNeoadjuvant chemotherapyEZH2 protein expressionEZH2 expressionBreast cancerHigh-risk triple negative breast cancerLogistic regressionContinuous variablesStratification of outcomesDisease-free survivalProtein expressionTumor-infiltrating lymphocytesHigh EZH2 expressionMultivariable logistic regressionRisk of relapseDevelopment of metastasesLogistic regression analysisPretherapy biopsiesDisease recurrenceMetastatic recurrenceClinicopathologic featuresCancer burdenTumor responseCore biopsy
2020
Histologic grading of breast carcinoma: a multi-institution study of interobserver variation using virtual microscopy
Ginter PS, Idress R, D’Alfonso T, Fineberg S, Jaffer S, Sattar AK, Chagpar A, Wilson P, Harigopal M. Histologic grading of breast carcinoma: a multi-institution study of interobserver variation using virtual microscopy. Modern Pathology 2020, 34: 701-709. PMID: 33077923, PMCID: PMC7987728, DOI: 10.1038/s41379-020-00698-2.Peer-Reviewed Original ResearchEpithelium Involving Bilateral Axillary Lymph Nodes: Metastasis, Misplaced, or Mullerian!
Singh K, Sardana R, Quddus MR, Harigopal M. Epithelium Involving Bilateral Axillary Lymph Nodes: Metastasis, Misplaced, or Mullerian! International Journal Of Surgical Pathology 2020, 29: 284-288. PMID: 32924678, DOI: 10.1177/1066896920958121.Peer-Reviewed Original ResearchConceptsSentinel lymph nodesBilateral axillary lymph nodesAxillary sentinel lymph nodesAxillary lymph nodesFrozen section examinationLymph nodesDifferential diagnosisEpithelial depositsSection examinationBreast cancer stagingNodal depositsCancer stagingHistological evaluationEpithelial restsEndosalpingiosisFirst caseDiagnosisEpitheliumExaminationMetastasisStagingMullerianEnumeration and molecular characterization of circulating tumor cells as an innovative tool for companion diagnostics in breast cancer
Harigopal M, Kowalski D, Vosoughi A. Enumeration and molecular characterization of circulating tumor cells as an innovative tool for companion diagnostics in breast cancer. Expert Review Of Molecular Diagnostics 2020, 20: 815-828. PMID: 32546017, DOI: 10.1080/14737159.2020.1784009.Peer-Reviewed Original ResearchConceptsBreast cancerTumor cellsCTC enumerationCTC detectionCTC clustersMetastatic breast cancerBreast cancer patientsEnumeration of CTCsOverall survivalRisk stratificationMetastatic sitesPeripheral bloodCancer patientsCTC levelsClinical backgroundPrimary siteClinical useCancerTumor phenotypeCompanion diagnosticsTumor heterogeneityDistant sitesMolecular characterizationPatientsPredictive importanceAdvances in quantitative immunohistochemistry and their contribution to breast cancer
Yaghoobi V, Martinez-Morilla S, Liu Y, Charette L, Rimm DL, Harigopal M. Advances in quantitative immunohistochemistry and their contribution to breast cancer. Expert Review Of Molecular Diagnostics 2020, 20: 509-522. PMID: 32178550, DOI: 10.1080/14737159.2020.1743178.Peer-Reviewed Original Research
2019
Interobserver variability in breast carcinoma grading results in prognostic stage differences
Rabe K, Snir OL, Bossuyt V, Harigopal M, Celli R, Reisenbichler ES. Interobserver variability in breast carcinoma grading results in prognostic stage differences. Human Pathology 2019, 94: 51-57. PMID: 31655171, DOI: 10.1016/j.humpath.2019.09.006.Peer-Reviewed Original ResearchConceptsPathologic prognostic stagePrognostic stageStage II carcinomaInterobserver variabilityIntra-observer variabilityGood intra-observer variabilityStage IABreast pathologistsConsecutive casesTumor gradeBreast carcinomaTumor gradingDiscordant gradesAJCC cancerDiscordant casesCarcinoma gradeInterobserver agreementGrading criteriaPathologistsCarcinomaComplete concordanceGradeOverall gradeGrading results
2018
Immunological differences between primary and metastatic breast cancer
Szekely B, Bossuyt V, Li X, Wali VB, Patwardhan GA, Frederick C, Silber A, Park T, Harigopal M, Pelekanou V, Zhang M, Yan Q, Rimm DL, Bianchini G, Hatzis C, Pusztai L. Immunological differences between primary and metastatic breast cancer. Annals Of Oncology 2018, 29: 2232-2239. PMID: 30203045, DOI: 10.1093/annonc/mdy399.Peer-Reviewed Original ResearchMeSH KeywordsAdolescentAdultAgedAntineoplastic Agents, ImmunologicalB7-H1 AntigenBiomarkers, TumorBiopsyBreast NeoplasmsDisease ProgressionDrug Resistance, NeoplasmFemaleGene Expression RegulationHumansImmunologic SurveillanceLymphocyte CountLymphocytes, Tumor-InfiltratingMiddle AgedMutation RateTumor EscapeTumor MicroenvironmentYoung AdultConceptsMetastatic breast cancerBreast cancerTherapeutic targetToll-like receptor pathway genesImmuno-oncology therapeutic targetsBreast cancer evolvesImmune proteasome expressionPD-L1 positivityCorresponding primary tumorsPotential therapeutic targetMHC class IImmune-related genesMetastatic cancer samplesLigand/receptor pairLymphocyte countT helperT-regsPD-L1Immune microenvironmentCytotoxic TPrimary tumorMastoid cellsDisease progressionTherapeutic combinationsMacrophage markersBreast cancer histopathology is predictive of low‐risk Oncotype Dx recurrence score
Wilson PC, Chagpar AB, Cicek AF, Bossuyt V, Buza N, Mougalian S, Killelea BK, Patel N, Harigopal M. Breast cancer histopathology is predictive of low‐risk Oncotype Dx recurrence score. The Breast Journal 2018, 24: 976-980. PMID: 30230117, DOI: 10.1111/tbj.13117.Peer-Reviewed Original ResearchConceptsLymph node-negative patientsNode-negative patientsOncotype DX testingInvasive carcinomaLow-grade invasive carcinomasHistologic subtypeOncotype DXRecurrence scoreEstrogen receptorHigh riskAJCC Breast Cancer Staging SystemBreast cancer staging systemOncotype DX recurrence scoreFavorable histologic subtypeOncotype recurrence scoreSimple multivariable modelsCancer (AJCC) staging systemRisk of recurrenceDX recurrence scoreOnly significant predictorExcellent prognosisIntermediate riskDuctal carcinomaHistologic gradeHistologic predictorsLoss of c-KIT expression in breast cancer correlates with malignant transformation of breast epithelium and is mediated by KIT gene promoter DNA hypermethylation
Janostiak R, Vyas M, Cicek AF, Wajapeyee N, Harigopal M. Loss of c-KIT expression in breast cancer correlates with malignant transformation of breast epithelium and is mediated by KIT gene promoter DNA hypermethylation. Experimental And Molecular Pathology 2018, 105: 41-49. PMID: 29852185, DOI: 10.1016/j.yexmp.2018.05.011.Peer-Reviewed Original ResearchConceptsC-kit expressionNormal breast tissueC-kitMalignant transformationReceptor tyrosine kinasesBreast tissueBreast cancer correlatesKIT proto-oncogene receptor tyrosine kinaseBreast cancer cell linesC-kit protein expressionBreast tumor developmentProto-oncogene receptor tyrosine kinaseBreast tumor samplesCancer cell linesNormal breast epithelial tissuesTyrosine kinaseBreast epithelial tissueCancer correlatesBreast malignancyC-kit mRNABreast epitheliumBreast tumorsTransmembrane receptor tyrosine kinaseCopy number alterationsTumor samplesStrong androgen receptor expression can aid in distinguishing GATA3+ metastases
Boto A, Harigopal M. Strong androgen receptor expression can aid in distinguishing GATA3+ metastases. Human Pathology 2018, 75: 63-70. PMID: 29408697, DOI: 10.1016/j.humpath.2018.01.024.Peer-Reviewed Original ResearchConceptsGATA3-positive tumorsAndrogen receptor expressionBreast originMetastatic settingUrothelial originAR expressionAR stainingAndrogen receptorReceptor expressionBreast cancerUnknown originBreast cancer tissue microarrayMarker of breastStrong AR expressionCancer tissue microarrayMammaglobin expressionUrothelial carcinomaLobular carcinomaProgesterone receptorEstrogen receptorTissue microarrayMammary originCarcinomaGATA3 expressionGATA3
2017
Impacts of Early Guideline-Directed 21-Gene Recurrence Score Testing on Adjuvant Therapy Decision Making
Dzimitrowicz H, Mougalian S, Storms S, Hurd S, Chagpar AB, Killelea BK, Horowitz NR, Lannin DR, Harigopal M, Hofstatter E, DiGiovanna MP, Adelson KB, Silber A, Abu-Khalaf M, Chung G, Zaheer W, Abdelghany O, Hatzis C, Pusztai L, Sanft TB. Impacts of Early Guideline-Directed 21-Gene Recurrence Score Testing on Adjuvant Therapy Decision Making. JCO Oncology Practice 2017, 13: jop.2017.022731. PMID: 29048991, DOI: 10.1200/jop.2017.022731.Peer-Reviewed Original ResearchConceptsAdjuvant therapy decisionsRecurrence scoreChemotherapy useRS testingMedical oncologistsHistorical controlsChemotherapy decisionsTherapy decisionsEligibility criteriaNational Comprehensive Cancer Network guidelinesProspective quality improvement projectEarly-stage breast cancerAdjuvant chemotherapy recommendationsTime of diagnosisTime of surgeryQuality improvement projectTesting groupChemotherapy initiationChemotherapy recommendationsMedian timeTrial enrollmentNetwork guidelinesSurgical oncologistsClinical trialsBreast cancer