2023
KRAS mutation in primary ovarian serous borderline tumors correlates with tumor recurrence
McHenry A, Rottmann D, Buza N, Hui P. KRAS mutation in primary ovarian serous borderline tumors correlates with tumor recurrence. Virchows Archiv 2023, 483: 71-79. PMID: 37219599, DOI: 10.1007/s00428-023-03564-z.Peer-Reviewed Original ResearchMeSH KeywordsCystadenocarcinoma, SerousCystadenoma, SerousFemaleHumansMutationNeoplasm Recurrence, LocalOvarian NeoplasmsProto-Oncogene Proteins B-rafProto-Oncogene Proteins p21(ras)ConceptsOvarian serous borderline tumorsSerous borderline tumorsNon-invasive implantsDisease-free survivalKRAS mutationsTumor recurrenceExtraovarian implantsAdverse disease-free survivalWorse disease-free survivalHigher stage diseaseKRAS mutation testingHigher tumor stageWild-type KRASBRAF V600E mutationBRAF mutational analysisBorderline tumorsClinical outcomesHistological subtypesTumor stageBRAF mutationsUseful biomarkerInvasive implantsTumors correlatesV600E mutationMutational status
2022
Characteristics of HER2 Gene Amplification by Fluorescence In Situ Hybridization in Endometrial Serous Carcinoma.
Buza N, Hui P. Characteristics of HER2 Gene Amplification by Fluorescence In Situ Hybridization in Endometrial Serous Carcinoma. Archives Of Pathology & Laboratory Medicine 2022, 146: 0. PMID: 35687792, DOI: 10.5858/arpa.2021-0547-oa.Peer-Reviewed Original ResearchConceptsEndometrial serous carcinomaClinical trial criteriaHER2 gene amplificationTrial criteriaHER2 immunohistochemistrySerous carcinomaAnti-human epidermal growth factor receptor 2 (HER2) therapyClinical Oncology/CollegeHER2 testing algorithmHER2 FISHProspective clinical investigationHER2 IHC 2HER2/CEP17Gene amplificationContext of breastTherapeutic responseIHC 2HER2 amplificationAverage HER2Most tumorsClinical investigationImmunohistochemistryHER2 fluorescenceTumorsMonosomy 17Synergistic 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
Minimal uterine serous carcinoma and endometrial polyp: a close clinicopathological relationship
Assem H, Rottmann D, Finkelstein A, Wang M, Ratner E, Santin AD, Buza N, Hui P. Minimal uterine serous carcinoma and endometrial polyp: a close clinicopathological relationship. Human Pathology 2021, 118: 1-8. PMID: 34508766, DOI: 10.1016/j.humpath.2021.09.001.Peer-Reviewed Original ResearchMeSH KeywordsAgedCystadenocarcinoma, SerousEndometrial NeoplasmsFemaleHumansMiddle AgedPolypsUterine NeoplasmsConceptsMinimal uterine serous carcinomaEndometrial polypsUterine serous carcinomaSerous carcinomaHigh stage patientsLow stage patientsPelvic washing cytologyAdvanced stage diseaseEndometrial serous carcinomaHigher stage diseaseLower tumor stageClinical outcome assessmentClose topographic relationshipBackground endometriumExtrauterine diseaseExtrauterine spreadStage diseaseExcellent prognosisLymphovascular invasionClinicopathological relationshipWashing cytologyTumor stageHigh riskPatientsLarge seriesDHES0815A, 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 variants
2020
Randomized Phase II Trial of Carboplatin–Paclitaxel Compared with Carboplatin–Paclitaxel–Trastuzumab in Advanced (Stage III–IV) or Recurrent Uterine Serous Carcinomas that Overexpress Her2/Neu (NCT01367002): Updated Overall Survival Analysis
Fader AN, Roque DM, Siegel E, Buza N, Hui P, Abdelghany O, Chambers S, Secord AA, Havrilesky L, O'Malley DM, Backes FJ, Nevadunsky N, Edraki B, Pikaart D, Lowery W, ElSahwi K, Celano P, Bellone S, Azodi M, Litkouhi B, Ratner E, Silasi DA, Schwartz PE, Santin AD. Randomized Phase II Trial of Carboplatin–Paclitaxel Compared with Carboplatin–Paclitaxel–Trastuzumab in Advanced (Stage III–IV) or Recurrent Uterine Serous Carcinomas that Overexpress Her2/Neu (NCT01367002): Updated Overall Survival Analysis. Clinical Cancer Research 2020, 26: 3928-3935. PMID: 32601075, PMCID: PMC8792803, DOI: 10.1158/1078-0432.ccr-20-0953.Peer-Reviewed Original ResearchMeSH KeywordsAgedAntineoplastic Combined Chemotherapy ProtocolsCarboplatinChemotherapy, AdjuvantCystadenocarcinoma, SerousCytoreduction Surgical ProceduresDrug Administration ScheduleEndometrial NeoplasmsEndometriumFemaleFollow-Up StudiesHumansMiddle AgedNeoplasm Recurrence, LocalNeoplasm StagingPaclitaxelProgression-Free SurvivalReceptor, ErbB-2Survival AnalysisTrastuzumabConceptsProgression-free survivalRandomized phase II trialPhase II trialOverall survivalHER2/neuStage IIICarboplatin-paclitaxelII trialRecurrent diseaseControl armSurvival analysisRecurrent uterine serous carcinomaCarboplatin/paclitaxelUterine serous carcinomaOverall survival analysisEvaluable patientsEligible patientsPrimary endpointSecondary endpointsEndometrial cancerAggressive variantSerous carcinomaPrimary treatmentSurvival medianPatients
2019
In vitro and in vivo activity of sacituzumab govitecan, an antibody-drug conjugate targeting trophoblast cell-surface antigen 2 (Trop-2) in uterine serous carcinoma
Han C, Perrone E, Zeybek B, Bellone S, Tymon-Rosario J, Altwerger G, Menderes G, Feinberg J, Haines K, Muller Karger ME, Bianchi A, Zammataro L, Manzano A, Bonazzoli E, Manara P, Buza N, Hui P, Ratner E, Silasi DA, Huang GS, Azodi M, Schwartz PE, Lopez S, Santin AD. In vitro and in vivo activity of sacituzumab govitecan, an antibody-drug conjugate targeting trophoblast cell-surface antigen 2 (Trop-2) in uterine serous carcinoma. Gynecologic Oncology 2019, 156: 430-438. PMID: 31839338, DOI: 10.1016/j.ygyno.2019.11.018.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsAntibodies, Monoclonal, HumanizedAntibody-Dependent Cell CytotoxicityAntigens, NeoplasmCamptothecinCell Adhesion MoleculesCell Line, TumorCystadenocarcinoma, SerousFemaleFlow CytometryHumansImmunoconjugatesImmunohistochemistryMiceMice, SCIDMolecular Targeted TherapyRandom AllocationTissue Array AnalysisUterine NeoplasmsXenograft Model Antitumor AssaysConceptsUterine serous carcinomaCell surface antigen 2Sacituzumab govitecanTrop-2 expressionTrop-2Serous carcinomaAntigen 2Advanced/recurrent diseasePrimary uterine serous carcinomaResistant human tumorsSignificant bystander killingUSC patientsUSC xenograftsRecurrent diseaseClinical responseEndometrial cancerAggressive variantPoor prognosisPreclinical activityPrimary tumorIntravenous administrationClinical developmentUSC samplesActive metaboliteSN-38
2018
Inhibition of BET Bromodomain Proteins with GS-5829 and GS-626510 in Uterine Serous Carcinoma, a Biologically Aggressive Variant of Endometrial Cancer
Bonazzoli E, Predolini F, Cocco E, Bellone S, Altwerger G, Menderes G, Zammataro L, Bianchi A, Pettinella F, Riccio F, Han C, Yadav G, Lopez S, Manzano A, Manara P, Buza N, Hui P, Wong S, Litkouhi B, Ratner E, Silasi DA, Huang GS, Azodi M, Schwartz PE, Schlessinger J, Santin AD. Inhibition of BET Bromodomain Proteins with GS-5829 and GS-626510 in Uterine Serous Carcinoma, a Biologically Aggressive Variant of Endometrial Cancer. Clinical Cancer Research 2018, 24: 4845-4853. PMID: 29941483, PMCID: PMC6168417, DOI: 10.1158/1078-0432.ccr-18-0864.Peer-Reviewed Original ResearchMeSH KeywordsAdultAgedAged, 80 and overAnimalsAntineoplastic AgentsApoptosisAurora Kinase AAurora Kinase BAzepinesCell Line, TumorCell ProliferationCystadenocarcinoma, SerousDose-Response Relationship, DrugEndometrial NeoplasmsExome SequencingFemaleGene Expression Regulation, NeoplasticHumansMiceMiddle AgedPhosphorylationPrimary Cell CultureProteinsProto-Oncogene Proteins c-mycTriazolesUterine NeoplasmsXenograft Model Antitumor AssaysConceptsUterine serous carcinomaPrimary USC cell linesUSC cell linesC-myc expressionCell linesC-MycChemotherapy-resistant diseaseQRT-PCRHigh c-myc expressionDose-dependent decreaseDose-dependent increasePotential therapeutic targetEffective therapeutic agentMouse xenograft modelClin Cancer ResFresh frozen tumor tissueC-myc gene amplificationUSC xenograftsEndometrial cancerAggressive variantSerous carcinomaWhole-exome sequencing studiesClinical studiesConcentrations/dosesXenograft modelRandomized Phase II Trial of Carboplatin-Paclitaxel Versus Carboplatin-Paclitaxel-Trastuzumab in Uterine Serous Carcinomas That Overexpress Human Epidermal Growth Factor Receptor 2/neu.
Fader AN, Roque DM, Siegel E, Buza N, Hui P, Abdelghany O, Chambers SK, Secord AA, Havrilesky L, O'Malley DM, Backes F, Nevadunsky N, Edraki B, Pikaart D, Lowery W, ElSahwi KS, Celano P, Bellone S, Azodi M, Litkouhi B, Ratner E, Silasi DA, Schwartz PE, Santin AD. Randomized Phase II Trial of Carboplatin-Paclitaxel Versus Carboplatin-Paclitaxel-Trastuzumab in Uterine Serous Carcinomas That Overexpress Human Epidermal Growth Factor Receptor 2/neu. Journal Of Clinical Oncology 2018, 36: 2044-2051. PMID: 29584549, DOI: 10.1200/jco.2017.76.5966.Peer-Reviewed Original ResearchConceptsHuman epidermal growth factor receptor 2Progression-free survivalUterine serous carcinomaRecurrent uterine serous carcinomaMedian progression-free survivalRandomized phase II trialEpidermal growth factor receptor 2Phase II trialGrowth factor receptor 2Serous carcinomaHER2/neuFactor receptor 2II trialTreatment armsReceptor 2Stage IIIHER2/neu-positive diseaseOne-sided log-rank testMethods Eligible patientsPrimary end pointPrimary stage IIIUnexpected safety signalsLog-rank testHumanized monoclonal antibodyEligible patients
2017
KRAS mutation of extraovarian implants of serous borderline tumor: prognostic indicator for adverse clinical outcome
Zuo T, Wong S, Buza N, Hui P. KRAS mutation of extraovarian implants of serous borderline tumor: prognostic indicator for adverse clinical outcome. Modern Pathology 2017, 31: 350-357. PMID: 29027536, DOI: 10.1038/modpathol.2017.121.Peer-Reviewed Original ResearchConceptsAtypical proliferative serous tumorNon-invasive implantsDisease-specific survivalSerous borderline tumorsHigh recurrence rateWorse disease-specific survivalStage IIIC diseaseKRAS mutationsInvasive implantsBRAF V600E mutationBorderline tumorsSerous tumorsRecurrence rateIIIC diseaseClinical outcomesHistological subtypesPrognostic indicatorExtraovarian implantsV600E mutationLow-grade serous carcinomaUnfavorable disease-specific survivalAdverse clinical outcomesHigher stage diseaseSignificant prognostic indicatorBRAF mutation frequency
2016
SYD985, a Novel Duocarmycin-Based HER2-Targeting Antibody–Drug Conjugate, Shows Antitumor Activity in Uterine Serous Carcinoma with HER2/Neu Expression
Black J, Menderes G, Bellone S, Schwab CL, Bonazzoli E, Ferrari F, Predolini F, De Haydu C, Cocco E, Buza N, Hui P, Wong S, Lopez S, Ratner E, Silasi DA, Azodi M, Litkouhi B, Schwartz PE, Goedings P, Beusker PH, van der Lee MM, Timmers CM, Dokter WH, Santin AD. SYD985, a Novel Duocarmycin-Based HER2-Targeting Antibody–Drug Conjugate, Shows Antitumor Activity in Uterine Serous Carcinoma with HER2/Neu Expression. Molecular Cancer Therapeutics 2016, 15: 1900-1909. PMID: 27256376, DOI: 10.1158/1535-7163.mct-16-0163.Peer-Reviewed Original ResearchMeSH KeywordsAdultAgedAged, 80 and overAnimalsAntibody-Dependent Cell CytotoxicityAntineoplastic AgentsBystander EffectCathepsin BCell Line, TumorCell SurvivalClass I Phosphatidylinositol 3-KinasesCystadenocarcinoma, SerousDisease Models, AnimalDuocarmycinsFemaleGene ExpressionHumansImmunoconjugatesIndolesMiceMiddle AgedMutationPhosphatidylinositol 3-KinasesPyrrolidinonesReceptor, ErbB-2Survival AnalysisUterine NeoplasmsXenograft Model Antitumor AssaysConceptsUterine serous carcinomaAntibody-dependent cellular cytotoxicityHER2/neu expressionAntibody-drug conjugatesT-DM1Neu expressionHER2-targeting antibody-drug conjugateNovel antibody-drug conjugateNovel HER2-targeting antibody-drug conjugatePrimary USC cell linesHigh HER2 expressionHER2/neu oncogeneHER2/neuMouse xenograft modelUSC cell linesFlow cytometry assayEndometrial cancerSerous carcinomaHER2 expressionTrastuzumab emtansineClinical studiesCellular cytotoxicitySYD985Aggressive formExpress HER2
2013
Toward standard HER2 testing of endometrial serous carcinoma: 4-year experience at a large academic center and recommendations for clinical practice
Buza N, English DP, Santin AD, Hui P. Toward standard HER2 testing of endometrial serous carcinoma: 4-year experience at a large academic center and recommendations for clinical practice. Modern Pathology 2013, 26: 1605-1612. PMID: 23765245, DOI: 10.1038/modpathol.2013.113.Peer-Reviewed Original ResearchConceptsEndometrial serous carcinomaSerous carcinomaHER2 overexpressionEndometrial carcinomaMedical recordsImmunohistochemical scoreHER2 testingProtein expressionHER2 immunohistochemistrySignificant heterogeneityScoring systemMultiple tumor sectionsPure serous carcinomaHER2-positive casesHER2-positive tumorsScoring criteriaEndometrial carcinoma casesFDA criteriaPatients' medical recordsLarge academic centerHER2 FISH resultsHER2 protein overexpressionPromising therapeutic targetOverall concordance rateHER2 immunohistochemical scores
2010
Overexpression of EpCAM in Uterine Serous Papillary Carcinoma: Implications for EpCAM-Specific Immunotherapy With Human Monoclonal Antibody Adecatumumab (MT201)
El-Sahwi K, Bellone S, Cocco E, Casagrande F, Bellone M, Abu-Khalaf M, Buza N, Tavassoli FA, Hui P, Rüttinger D, Silasi DA, Azodi M, Schwartz PE, Rutherford TJ, Pecorelli S, Santin AD. Overexpression of EpCAM in Uterine Serous Papillary Carcinoma: Implications for EpCAM-Specific Immunotherapy With Human Monoclonal Antibody Adecatumumab (MT201). Molecular Cancer Therapeutics 2010, 9: 57-66. PMID: 20053761, PMCID: PMC2806489, DOI: 10.1158/1535-7163.mct-09-0675.Peer-Reviewed Original ResearchMeSH KeywordsAgedAntibodies, MonoclonalAntibodies, Monoclonal, HumanizedAntibody-Dependent Cell CytotoxicityAntigens, NeoplasmCarcinoma, PapillaryCell Adhesion MoleculesCell Line, TumorCell MembraneCystadenocarcinoma, SerousDrug Resistance, NeoplasmDrug Screening Assays, AntitumorEpithelial Cell Adhesion MoleculeFemaleFlow CytometryGene Expression Regulation, NeoplasticHumansImmunoglobulin GImmunohistochemistryImmunotherapyInterleukin-2Killer Cells, NaturalMiddle AgedNeoplasm MetastasisRNA, MessengerUterine NeoplasmsConceptsUterine serous papillary carcinomaUSPC cell linesNormal endometrial cellsPrimary USPC cell linesAntibody-dependent cellular cytotoxicitySerous papillary carcinomaCellular cytotoxicityPapillary carcinomaCell linesFlow cytometryAdvanced/recurrentStandard treatment modalityCell-dependent cytotoxicityUterine serous carcinomaComplement-dependent cytotoxicitySurface expressionHuman monoclonal antibodyNovel therapeutic strategiesFresh frozen biopsiesHigh surface expressionEpithelial cell adhesion moleculeOverexpression of EpCAMParaffin-embedded tissuesMedian copy numberSerous carcinoma
2005
Improved survival in surgical stage I patients with uterine papillary serous carcinoma (UPSC) treated with adjuvant platinum-based chemotherapy
Kelly MG, O'Malley DM, Hui P, McAlpine J, Yu H, Rutherford TJ, Azodi M, Schwartz PE. Improved survival in surgical stage I patients with uterine papillary serous carcinoma (UPSC) treated with adjuvant platinum-based chemotherapy. Gynecologic Oncology 2005, 98: 353-359. PMID: 16005947, DOI: 10.1016/j.ygyno.2005.06.012.Peer-Reviewed Original ResearchMeSH KeywordsAgedAntineoplastic Combined Chemotherapy ProtocolsBiopsy, NeedleChemotherapy, AdjuvantCystadenocarcinoma, PapillaryCystadenocarcinoma, SerousDilatation and CurettageDisease-Free SurvivalFemaleHumansHysterectomyNeoplasm StagingOrganoplatinum CompoundsRetrospective StudiesUterine NeoplasmsConceptsUterine papillary serous carcinomaPlatinum-based chemotherapyResidual uterine diseaseStage IA patientsVaginal cuff radiationAdjuvant platinum-based chemotherapySurgical stage IPapillary serous carcinomaIA patientsUterine diseaseStage IHysterectomy specimenOverall survivalSerous carcinomaConcomitant platinum-based chemotherapyImproved disease-free survivalComplete surgical stagingStage IB patientsStage IC patientsDisease-free survivalHigh recurrence rateVaginal radiationAdjuvant therapyStage IASurgical stagingMinimal uterine serous carcinoma: a clinicopathological study of 40 cases
Hui P, Kelly M, O'Malley DM, Tavassoli F, Schwartz PE. Minimal uterine serous carcinoma: a clinicopathological study of 40 cases. Modern Pathology 2005, 18: 75-82. PMID: 15389257, DOI: 10.1038/modpathol.3800271.Peer-Reviewed Original ResearchConceptsMinimal uterine serous carcinomaUterine serous carcinomaSerous carcinomaEndometrial polypsExtrauterine tumorsInvasive serous carcinomasSurgical staging procedureHigh nuclear gradeSurgical stagingClinicopathological studyOverall survivalStaging procedureClinical outcomesClinicopathologic featuresStromal invasionImmunohistochemical profileNuclear gradeMutant p53 proteinCarcinomaPatientsPolypsTumorsP53 proteinLesionsInvasion
2004
Patients with uterine papillary serous cancers may benefit from adjuvant platinum-based chemoradiation
Kelly MG, O'Malley D, Hui P, McAlpine J, Dziura J, Rutherford TJ, Azodi M, Chambers SK, Schwartz PE. Patients with uterine papillary serous cancers may benefit from adjuvant platinum-based chemoradiation. Gynecologic Oncology 2004, 95: 469-473. PMID: 15581948, DOI: 10.1016/j.ygyno.2004.08.030.Peer-Reviewed Original ResearchConceptsUterine papillary serous carcinomaStage IA patientsResidual uterine diseaseAdvanced stage uterine papillary serous carcinomaIA patientsUterine diseaseSerous cancerUterine papillary serous cancerComplete surgical stagingObstetrics stage IAPapillary serous cancerDifferent therapeutic optionsPapillary serous carcinomaPlatinum-based chemoradiationMore effective treatmentsLocoregional diseaseHysterectomy specimenStage IAStage IIIAStage IIICSurgical stagingExtrauterine metastasesSerous carcinomaTherapeutic optionsFallopian tube