2022
Data Set for the Reporting of Endometrial Cancer: Recommendations From the International Collaboration on Cancer Reporting (ICCR)
Matias-Guiu X, Selinger CI, Anderson L, Buza N, Ellenson LH, Fadare O, Ganesan R, Ip PPC, Palacios J, Parra-Herran C, Raspollini MR, Soslow RA, Werner HMJ, Lax SF, McCluggage WG. Data Set for the Reporting of Endometrial Cancer: Recommendations From the International Collaboration on Cancer Reporting (ICCR). International Journal Of Gynecological Pathology 2022, 41: s90-s118. PMID: 36305536, DOI: 10.1097/pgp.0000000000000901.Peer-Reviewed Original ResearchConceptsEndometrial cancerCancer reportingWorld Health Organization classificationFemale genital tumorsCancer patient careCommon cancerOrganization classificationResection specimensClinical managementGenital tumorsPatient careCancerMolecular classificationCancer diagnosisExpert cliniciansExpert pathologistsNoncore elementsMajor advancesDetailed recommendationsReportingCancer dataInternational collaborationPrognosisNeoplasmsTumorsSynergistic activity of neratinib in combination with olaparib in uterine serous carcinoma overexpressing HER2/neu
Yadav G, Roque DM, Bellone S, Manavella DD, Hartwich TMP, Zipponi M, Harold J, Tymon-Rosario J, Mutlu L, Altwerger G, Menderes G, Ratner E, Buza N, Hui P, Huang GS, Andikyan V, Clark M, Azodi M, Schwartz PE, Alexandrov LB, Santin AD. Synergistic activity of neratinib in combination with olaparib in uterine serous carcinoma overexpressing HER2/neu. Gynecologic Oncology 2022, 166: 351-357. PMID: 35641325, DOI: 10.1016/j.ygyno.2022.05.021.Peer-Reviewed Original ResearchConceptsUterine serous carcinomaHER2/neu expressionHER2/neuCombination of olaparibUSC xenograftsUSC cell linesNeu expressionSerous carcinomaLow HER2/neu expressionHER2/neu 3Cell linesHER2/neu gene amplificationNovel therapeutic optionsPolymerase inhibitor olaparibNeu gene amplificationDurable growth inhibitionNeratinib treatmentUSC cellsUSC patientsEndometrial cancerAggressive variantTherapeutic optionsPoor prognosisHER2/Single agent
2021
A phase 2 evaluation of pembrolizumab for recurrent Lynch‐like versus sporadic endometrial cancers with microsatellite instability
Bellone S, Roque DM, Siegel ER, Buza N, Hui P, Bonazzoli E, Guglielmi A, Zammataro L, Nagarkatti N, Zaidi S, Lee J, Silasi D, Huang GS, Andikyan V, Damast S, Clark M, Azodi M, Schwartz PE, Tymon‐Rosario J, Harold JA, Mauricio D, Zeybek B, Menderes G, Altwerger G, Ratner E, Alexandrov LB, Iwasaki A, Kong Y, Song E, Dong W, Elvin JA, Choi J, Santin AD. A phase 2 evaluation of pembrolizumab for recurrent Lynch‐like versus sporadic endometrial cancers with microsatellite instability. Cancer 2021, 128: 1206-1218. PMID: 34875107, PMCID: PMC9465822, DOI: 10.1002/cncr.34025.Peer-Reviewed Original ResearchConceptsObjective response rateImmune checkpoint inhibitorsProgression-free survivalEndometrial cancerWhole-exome sequencingSporadic endometrial cancerOverall survivalEnd pointPhase 2 pilot studyPrimary end pointSecondary end pointsTumor mutation burdenPhase 2 evaluationLarger confirmatory studiesAntigen processing/presentationProcessing/presentationCheckpoint inhibitorsSurgical resectionICI resistanceDMMR patientsPrognostic significanceDMMR tumorsMechanisms of resistanceLocal treatmentSporadic MSIDHES0815A, a novel antibody-drug conjugate targeting HER2/neu, is highly active against uterine serous carcinomas in vitro and in vivo
Tymon-Rosario J, Bonazzoli E, Bellone S, Manzano A, Pelligra S, Guglielmi A, Gnutti B, Nagarkatti N, Zeybek B, Manara P, Zammataro L, Harold J, Mauricio D, Buza N, Hui P, Altwerger G, Menderes G, Ratner E, Clark M, Andikyan V, Huang GS, Silasi DA, Azodi M, Schwartz PE, Santin AD. DHES0815A, a novel antibody-drug conjugate targeting HER2/neu, is highly active against uterine serous carcinomas in vitro and in vivo. Gynecologic Oncology 2021, 163: 334-341. PMID: 34452746, PMCID: PMC8722447, DOI: 10.1016/j.ygyno.2021.08.014.Peer-Reviewed Original ResearchMeSH KeywordsAdultAgedAged, 80 and overAntibodies, Monoclonal, HumanizedBenzodiazepinesBystander EffectCell Line, TumorCystadenocarcinoma, SerousDrug Resistance, NeoplasmFemaleHumansImmunoconjugatesMiddle AgedPrimary Cell CultureReceptor, ErbB-2TrastuzumabUterine NeoplasmsXenograft Model Antitumor AssaysConceptsHER2/neuPrimary USC cell linesUSC cell linesUterine serous carcinomaSerous carcinomaHER2/Cell linesBystander killingHER2/neu protein expressionHER2/neu overexpressionProtein expressionNovel treatment optionsAggressive histologic variantNeu protein expressionHER2 protein expressionC-erbB2 gene amplificationSignificant bystander killingUSC xenograftsEndometrial cancerNegative tumorsPoor prognosisPositive tumorsTreatment optionsPreclinical activityHistologic variantsIntraoperative Consultation
Buza N, Euscher E. Intraoperative Consultation. Practical Anatomic Pathology 2021, 317-343. DOI: 10.1007/978-3-030-68608-6_13.Peer-Reviewed Original ResearchFuture fertilityCommon differential diagnostic considerationsIntraoperative frozen section evaluationIntraoperative consultationExtent of surgeryFrozen section evaluationClinical differential diagnosisPatient's future fertilityPreoperative diagnostic workupDifferential diagnostic considerationsFrozen section laboratoryEndometrial cancerOvarian neoplasmsPelvic massCervical carcinomaDiagnostic workupGynecologic pathologyMalignant entitiesDiagnostic challengeSurgical specimensDiagnostic considerationsDifferential diagnosisPathology evaluationSurgical teamDisease typeHER2 Expression in Endometrial Cancers Diagnosed as Clear Cell Carcinoma
Cagaanan A, Stelter B, Vu N, Rhode EN, Stewart T, Hui P, Buza N, Al-Niaimi A, Flynn C, Weisman PS, McGregor SM. HER2 Expression in Endometrial Cancers Diagnosed as Clear Cell Carcinoma. International Journal Of Gynecological Pathology 2021, 41: 132-141. PMID: 33782344, DOI: 10.1097/pgp.0000000000000783.Peer-Reviewed Original ResearchConceptsClear cell carcinomaEndometrial cancerSerous carcinomaCell carcinomaDiagnosis of CCCTraditional histologic classificationFuture clinical trialsAberrant p53 stainingBattery of immunostainsMajor diagnostic considerationCCC diagnosisMost HER2ER expressionEndometrioid carcinomaGynecologic pathologistsBeneficial therapyHER2 expressionHER2 statusP53 stainingClinical trialsDiagnostic difficultiesHistologic classificationDiagnostic considerationsAberrant p53Tissue microarrayReproducibility of scoring criteria for HER2 immunohistochemistry in endometrial serous carcinoma: a multi-institutional interobserver agreement study
Buza N, Euscher ED, Matias-Guiu X, McHenry A, Oliva E, Ordulu Z, Parra-Herran C, Rottmann D, Turner BM, Wong S, Hui P. Reproducibility of scoring criteria for HER2 immunohistochemistry in endometrial serous carcinoma: a multi-institutional interobserver agreement study. Modern Pathology 2021, 34: 1194-1202. PMID: 33536574, DOI: 10.1038/s41379-021-00746-5.Peer-Reviewed Original ResearchConceptsEndometrial serous carcinomaHER2 scoring criteriaSerous carcinomaHER2 scoreGynecologic pathologistsAnti-human epidermal growth factor receptor 2 (HER2) therapyRecent successful clinical trialsInterobserver disagreementCombination of HER2Successful clinical trialsHER2 gene amplificationInterobserver agreement studyScoring criteriaInterobserver agreement ratesOverall survivalEndometrial cancerPathologic studiesHER2 statusClinical trialsGastric carcinomaHER2 testingHER2 immunohistochemistryAdvanced stageCarcinomaScoring system
2020
HER2 Testing in Endometrial Serous Carcinoma: Time for Standardized Pathology Practice to Meet the Clinical Demand
Buza N. HER2 Testing in Endometrial Serous Carcinoma: Time for Standardized Pathology Practice to Meet the Clinical Demand. Archives Of Pathology & Laboratory Medicine 2020, 145: 687-691. PMID: 32649220, DOI: 10.5858/arpa.2020-0207-ra.Peer-Reviewed Original ResearchConceptsEndometrial serous carcinomaSerous carcinomaHER2 protein expressionHER2 testingNational Comprehensive Cancer Network clinical guidelinesProlonged progression-free survivalHuman epidermal growth factor receptor 2Epidermal growth factor receptor 2Gene amplificationStandard chemotherapy regimenProgression-free survivalProtein expressionAppropriate patient selectionGrowth factor receptor 2Recent clinical trialsSuccessful clinical outcomeHER2 protein overexpressionFactor receptor 2HER2 scoring criteriaHER2 therapyChemotherapy regimenEndometrial cancerClinical outcomesPatient selectionAggressive subtypeSelection of HER2/NEU negative tumor cells as a mechanism of resistance to trastuzumab in uterine serous carcinoma
Pelligra S, Buza N, Hui P, Bellone S, Zeybek B, Ratner E, Schwartz PE, Scambia G, Santin AD. Selection of HER2/NEU negative tumor cells as a mechanism of resistance to trastuzumab in uterine serous carcinoma. Gynecologic Oncology Reports 2020, 32: 100554. PMID: 32140533, PMCID: PMC7049633, DOI: 10.1016/j.gore.2020.100554.Peer-Reviewed Original ResearchUterine serous carcinomaHER2/neuNegative tumor cellsUSC patientsTumor cellsSerous carcinomaHER2/neu overexpressionCarboplatin/paclitaxelInitial clinical responsePost-treatment biopsiesHumanized monoclonal antibodyC-erbB2 gene amplificationNCCN guidelinesClinical responseEndometrial cancerPreferred regimenAggressive variantMechanisms of resistanceNeu overexpressionRecurrent/HER2/TrastuzumabPatientsMonoclonal antibodiesNeuFrequent loss of mutation-specific mismatch repair protein expression in nonneoplastic endometrium of Lynch syndrome patients
Wong S, Hui P, Buza N. Frequent loss of mutation-specific mismatch repair protein expression in nonneoplastic endometrium of Lynch syndrome patients. Modern Pathology 2020, 33: 1172-1181. PMID: 31932681, DOI: 10.1038/s41379-020-0455-x.Peer-Reviewed Original ResearchConceptsLynch syndrome patientsLynch syndromeMMR protein expressionSporadic endometrial carcinomasSyndrome patientsEndometrial cancerEndometrial glandsEndometrial carcinomaProtein expressionLynch syndrome-associated endometrial cancerGermline mutationsMismatch repair protein expressionMMR protein immunohistochemistryEndometrial cancer patientsNonneoplastic endometriumBenign endometrial tissuesMicrosatellite instability testingMMR protein lossGermline mutation analysisDNA mismatch repair genesRepair protein expressionMismatch repair genesBackground endometriumMMR immunohistochemistryProphylactic hysterectomy
2018
Minimal microsatellite shift in microsatellite instability high endometrial cancer: a significant pitfall in diagnostic interpretation
Wu X, Snir O, Rottmann D, Wong S, Buza N, Hui P. Minimal microsatellite shift in microsatellite instability high endometrial cancer: a significant pitfall in diagnostic interpretation. Modern Pathology 2018, 32: 650-658. PMID: 30443012, DOI: 10.1038/s41379-018-0179-3.Peer-Reviewed Original ResearchMeSH KeywordsAgedAged, 80 and overBiomarkers, TumorColorectal Neoplasms, Hereditary NonpolyposisDNA-Binding ProteinsEndometrial NeoplasmsFemaleGenetic LociGenetic Predisposition to DiseaseHumansImmunohistochemistryMicrosatellite InstabilityMiddle AgedMismatch Repair Endonuclease PMS2MutL Protein Homolog 1MutS Homolog 2 ProteinPhenotypePolymerase Chain ReactionPredictive Value of TestsReproducibility of ResultsConceptsEndometrial cancerMLH1/PMS2Endometrial carcinomaMSH6 lossMicrosatellite shiftCancer cohortMismatch repair deficiency testingMicrosatellite instability-high colorectal cancerEndometrial cancer cohortLoss of PMS2Clear cell carcinomaColorectal cancer cohortHigh colorectal cancerLynch syndrome familiesMSH2/MSH6PMS2 lossCell carcinomaColorectal cancerDeficiency testingSolid malignanciesColorectal carcinomaCarcinomaCancerIsolated lossMSH-6
2015
HER2 as Biomarker for Endometrial Cancer
English D, Roque D, Buza N, Santin A. HER2 as Biomarker for Endometrial Cancer. Biomarkers In Disease: Methods, Discoveries And Applications 2015, 507-526. DOI: 10.1007/978-94-007-7681-4_26.ChaptersEndometrial cancerEpidermal growth factor (EGF) familyGrowth factor familyC-erbB2 geneFactor familyCell survivalErbB pathwayNovel tyrosine kinase inhibitorOverall poor survivalOverexpression of HER2Tyrosine kinase inhibitorsKinase inhibitorsEndometrial neoplasmsPoor survivalPathwayTumor typesHER2Monoclonal antibodiesCancerGenesBiomarkersOverexpressionSurvivalWide varietyErbB2
2014
HER2/neu in Endometrial Cancer: A Promising Therapeutic Target With Diagnostic Challenges
Buza N, Roque DM, Santin AD. HER2/neu in Endometrial Cancer: A Promising Therapeutic Target With Diagnostic Challenges. Archives Of Pathology & Laboratory Medicine 2014, 138: 343-50. PMID: 24576030, DOI: 10.5858/arpa.2012-0416-ra.Peer-Reviewed Original ResearchConceptsEndometrial carcinomaHER2/neuPromising therapeutic targetHER2 testingClinical responseTherapeutic targetHumanized monoclonal immunoglobulin G1 antibodyMonoclonal immunoglobulin G1 antibodyUterine serous carcinomaImmunoglobulin G1 antibodyNovel therapeutic strategiesEndometrial cancerSerous adenocarcinomaSerous carcinomaCase reportDiagnostic challengeHER2 overexpressionPathogenetic featuresClinical studiesG1 antibodyTherapeutic strategiesCarcinomaTherapeutic efficacyStandardized criteriaTherapyHER2 as Biomarker for Endometrial Cancer
English D, Roque D, Buza N, Santin A. HER2 as Biomarker for Endometrial Cancer. 2014, 1-16. DOI: 10.1007/978-94-007-7744-6_26-1.ChaptersEndometrial cancerEpidermal growth factor (EGF) familyGrowth factor familyC-erbB2 geneFactor familyCell survivalErbB pathwayNovel tyrosine kinase inhibitorOverall poor survivalOverexpression of HER2Tyrosine kinase inhibitorsKinase inhibitorsEndometrial neoplasmsPoor survivalPathwayTumor typesHER2Monoclonal antibodiesCancerGenesBiomarkersOverexpressionSurvivalWide varietyErbB2