2024
Randomized Phase II Trial of Imiquimod with or without 9-Valent HPV Vaccine versus Observation in Patients with High-grade Pre-neoplastic Cervical Lesions (NCT02864147)
Sheth S, Oh J, Bellone S, Siegel E, Greenman M, Mutlu L, McNamara B, Pathy S, Clark M, Azodi M, Altwerger G, Andikyan V, Huang G, Ratner E, Kim D, Iwasaki A, Levi A, Buza N, Hui P, Flaherty S, Schwartz P, Santin A. Randomized Phase II Trial of Imiquimod with or without 9-Valent HPV Vaccine versus Observation in Patients with High-grade Pre-neoplastic Cervical Lesions (NCT02864147). Clinical Cancer Research 2024, 30: of1-of10. PMID: 38592381, DOI: 10.1158/1078-0432.ccr-23-3639.Peer-Reviewed Original ResearchConceptsRandomized phase II trialCD4/CD8 T cellsT cellsHPV clearanceArm BNo significant differenceClinical surveillanceRate of HPV clearanceSecondary outcomesPre-neoplastic cervical lesionsCervical intraepithelial neoplasiaT cell infiltrationT cell responsesSignificant differenceCIN3 patientsIntraepithelial neoplasiaArm ACervical lesionsImiquimod groupSurveillance armVaginal suppositoriesProspective trialsArm CHPV vaccinationImiquimod
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 variantsReproducibility 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
Does Specimen Type Have an Impact on HER2 Status in Endometrial Serous Carcinoma? Discordant HER2 Status of Paired Endometrial Biopsy and Hysterectomy Specimens in the Presence of Frequent Intratumoral Heterogeneity
Rottmann D, Assem H, Matsumoto N, Wong S, Hui P, Buza N. Does Specimen Type Have an Impact on HER2 Status in Endometrial Serous Carcinoma? Discordant HER2 Status of Paired Endometrial Biopsy and Hysterectomy Specimens in the Presence of Frequent Intratumoral Heterogeneity. International Journal Of Gynecological Pathology 2020, 40: 263-271. PMID: 32897955, DOI: 10.1097/pgp.0000000000000690.Peer-Reviewed Original ResearchConceptsEndometrial serous carcinomaDiscordant HER2 statusHER2 immunohistochemical scoresHER2 protein expressionSerous carcinomaHER2 statusEndometrial biopsies/curettingsImmunohistochemical scoreProtein expressionHER2 testingIntratumoral heterogeneityEndometrial biopsy/curettageProlonged progression-free survivalHuman epidermal growth factor receptor 2Epidermal growth factor receptor 2HER2 testing algorithmProgression-free survivalGrowth factor receptor 2HER2-negative tumorsFinal study cohortHER2-positive tumorsRecent clinical trialsSpecimen typesFactor receptor 2Optimal specimen typesHuman epidermal growth factor 2 (HER2) in early stage uterine serous carcinoma: A multi-institutional cohort study
Erickson BK, Najjar O, Damast S, Blakaj A, Tymon-Rosario J, Shahi M, Santin A, Klein M, Dolan M, Cimino-Mathews A, Buza N, Ferriss JS, Stone RL, Khalifa M, Fader AN. Human epidermal growth factor 2 (HER2) in early stage uterine serous carcinoma: A multi-institutional cohort study. Gynecologic Oncology 2020, 159: 17-22. PMID: 32709539, PMCID: PMC7541557, DOI: 10.1016/j.ygyno.2020.07.016.Peer-Reviewed Original ResearchMeSH KeywordsAgedAntineoplastic Combined Chemotherapy ProtocolsBiomarkers, TumorChemoradiotherapy, AdjuvantCystadenocarcinoma, SerousFemaleFollow-Up StudiesHumansHysterectomyImmunohistochemistryMiddle AgedNeoplasm InvasivenessNeoplasm Recurrence, LocalNeoplasm StagingPrognosisProgression-Free SurvivalReceptor, ErbB-2Retrospective StudiesRisk AssessmentUnited StatesUterine NeoplasmsUterusConceptsHuman epidermal growth factor 2Uterine serous carcinomaHER2-positive tumorsEarly-stage diseaseOverall survivalSerous carcinomaCohort studyHER2 positivityPositive tumorsEarly stage uterine serous carcinomaLymph-vascular space invasionRecurrent uterine serous carcinomaMulti-institutional cohort studyHuman epidermal growth factor receptor 2Multi-center cohort studyEpidermal growth factor receptor 2Epidermal growth factor 2HER2-positive cohortGrowth factor receptor 2HER2-negative tumorsEquivocal IHC resultsFactor receptor 2Inferior PFSAdjuvant therapyGrowth factor 2Molecular and clinicopathologic characterization of intravenous leiomyomatosis
Ordulu Z, Chai H, Peng G, McDonald AG, De Nictolis M, Garcia-Fernandez E, Hardisson D, Prat J, Li P, Hui P, Oliva E, Buza N. Molecular and clinicopathologic characterization of intravenous leiomyomatosis. Modern Pathology 2020, 33: 1844-1860. PMID: 32341498, PMCID: PMC7483566, DOI: 10.1038/s41379-020-0546-8.Peer-Reviewed Original ResearchConceptsIntravenous leiomyomatosisAggressive clinical behaviorClinical behaviorArray comparative genomic hybridizationCyclin D1Uterine smooth muscle tumorsSmooth muscle tumorsSmooth muscle proliferationRecurrent chromosome alterationsCommon genetic alterationsFH immunohistochemistryClinicopathologic characterizationImmunohistochemical findingsMesenchymal tumorsMuscle tumorsBenign appearanceMuscle proliferationUterine leiomyomaGroup 1Group 3Nonneoplastic tissuesIndex scoreVascular morphologyProtein expressionComparative genomic hybridizationFrequent 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 hysterectomyPhase II evaluation of nivolumab in the treatment of persistent or recurrent cervical cancer (NCT02257528/NRG-GY002)
Santin AD, Deng W, Frumovitz M, Buza N, Bellone S, Huh W, Khleif S, Lankes HA, Ratner ES, O'Cearbhaill RE, Jazaeri AA, Birrer M. Phase II evaluation of nivolumab in the treatment of persistent or recurrent cervical cancer (NCT02257528/NRG-GY002). Gynecologic Oncology 2020, 157: 161-166. PMID: 31924334, PMCID: PMC7127981, DOI: 10.1016/j.ygyno.2019.12.034.Peer-Reviewed Original ResearchConceptsTreatment-related adverse eventsRecurrent cervical cancerPD-L1 expressionPlatinum-based chemotherapyCervical cancerStable diseaseGrade 3 treatment-related adverse eventsGrade 4 treatment-related adverse eventsGrade 5 treatment-related adverse eventsECOG PS 0Prior systemic therapyRecurrent cervical carcinomaResponse/toxicitySingle-agent nivolumabSystemic chemotherapy regimenTolerability of nivolumabImmune checkpoint inhibitorsPercent of patientsAcceptable safety profilePhase II trialKey eligibility criteriaPhase II evaluationECOG PSNivolumab 3RECIST 1.1
2019
HER2 testing of gynecologic carcinosarcomas: tumor stratification for potential targeted therapy
Rottmann D, Snir OL, Wu X, Wong S, Hui P, Santin AD, Buza N. HER2 testing of gynecologic carcinosarcomas: tumor stratification for potential targeted therapy. Modern Pathology 2019, 33: 118-127. PMID: 31477811, DOI: 10.1038/s41379-019-0358-x.Peer-Reviewed Original ResearchConceptsEndometrial serous carcinomaHER2-positive tumorsSerous carcinomaSarcoma componentHER2 statusGynecologic carcinosarcomaHER2 expression/amplificationRecent phase II clinical trialPhase II clinical trialCarboplatin-paclitaxel chemotherapyEquivocal HER2 expressionProgression-free survivalAppropriate patient selectionExpression/amplificationFemale genital tractMembranous staining patternHER2 protein expressionHER2 immunohistochemical scoresUterine primaryDismal prognosisPatient selectionCarcinoma componentMixed carcinomasHER2 expressionClinical trialsPrecision genotyping diagnosis of lung tumors with trophoblastic morphology in young women
Buza N, Baine I, Hui P. Precision genotyping diagnosis of lung tumors with trophoblastic morphology in young women. Modern Pathology 2019, 32: 1271-1280. PMID: 31028360, DOI: 10.1038/s41379-019-0275-z.Peer-Reviewed Original ResearchConceptsGestational choriocarcinomaLung carcinomaLung massClinical historyLung tumorsGestational originSerum beta-hCG levelsYoung womenTrophoblastic differentiationMetastatic gestational choriocarcinomaSerum beta-hCGBeta-hCG levelsEvidence of diseaseUnique diagnostic challengePrimary lung carcinomaGestational trophoblastic neoplasiaDifferent chemotherapeutic regimensDifferent primary sitesWedge resectionBeta-hCGFemale patientsMetastatic choriocarcinomaThird patientChemotherapeutic regimensImmunophenotypical features
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
2017
Ovarian Sertoli-Leydig cell tumors: a single institution experience and review of the literature.
Gressel G, Buza N, Pal L. Ovarian Sertoli-Leydig cell tumors: a single institution experience and review of the literature. European Journal Of Gynaecological Oncology 2017, 38: 214-220. PMID: 29953783.Peer-Reviewed Original ResearchMeSH KeywordsAdolescentAdultAgedAged, 80 and overAntineoplastic Combined Chemotherapy ProtocolsChemotherapy, AdjuvantDisease-Free SurvivalFemaleHumansHyperandrogenismHysterectomyMiddle AgedNeoadjuvant TherapyNeoplasm GradingOvarian NeoplasmsOvariectomyPostmenopauseRetrospective StudiesSalpingectomySertoli-Leydig Cell TumorConceptsSertoli-Leydig cell tumorOvarian Sertoli-Leydig cell tumorPresent patient populationDisease-free survivalSingle institution experienceTertiary care institutionTime of diagnosisOnset of menopauseRisk of recurrenceSeries of casesAdjuvant chemotherapyMedian followPostmenopausal bleedingPostmenopausal patientsMedian ageMedian intervalClinical presentationDefinitive managementPathological findingsRetrospective reviewInstitution experiencePatient populationTreatment modalitiesCell tumorsTumor grade
2015
Diagnostic application of KRAS mutation testing in uterine microglandular proliferations
Hong W, Abi-Raad R, Alomari AK, Hui P, Buza N. Diagnostic application of KRAS mutation testing in uterine microglandular proliferations. Human Pathology 2015, 46: 1000-1005. PMID: 25997988, DOI: 10.1016/j.humpath.2015.03.010.Peer-Reviewed Original ResearchMeSH KeywordsAdenocarcinomaAdultAgedAged, 80 and overBiopsyCell ProliferationCervix UteriDiagnosis, DifferentialDNA Mutational AnalysisEndometrial HyperplasiaEndometrial NeoplasmsFemaleHumansMiddle AgedMutationPredictive Value of TestsProto-Oncogene ProteinsProto-Oncogene Proteins p21(ras)Ras ProteinsConceptsKRAS mutation analysisEndometrial adenocarcinomaMicroglandular hyperplasiaMicroglandular patternKRAS mutationsCareful morphological assessmentEndometrial mucinous carcinomaKRAS mutation testingCases of EMAMutation analysisFrequent KRAS mutationsElectronic medical recordsDifferential diagnostic toolHigh mitotic activityEndometrial biopsyImmunohistochemical workupUterine cervixMucinous carcinomaClinical historyDiagnostic challengeDiagnostic dilemmaGlandular proliferationMucinous lesionsMedical recordsEAC casesIntravenous Leiomyomatosis Revisited
Carr RJ, Hui P, Buza N. Intravenous Leiomyomatosis Revisited. International Journal Of Gynecological Pathology 2015, 34: 169-176. PMID: 25675187, DOI: 10.1097/pgp.0000000000000127.Peer-Reviewed Original ResearchMeSH KeywordsAdultBroad LigamentFemaleHumansLeiomyomatosisMiddle AgedMuscle, SmoothUterine NeoplasmsVeinsConceptsIntravenous leiomyomatosisSmooth muscle originMuscle originCases of IVLCommon extrauterine siteRight heart chambersGood overall prognosisPatients' medical recordsDirect mass effectGross pathologic findingsConventional diagnostic criteriaExtrauterine extensionExtrauterine involvementClinical sequelaeOverall prognosisDisease recurrenceMedian agePatient agePrompt diagnosisInitial diagnosisPathologic findingsSignificant morbiditySurgical excisionInferior venaPrimary lesion
2014
Mitotically Active Microglandular Hyperplasia of the Cervix
Abi-Raad R, Alomari A, Hui P, Buza N. Mitotically Active Microglandular Hyperplasia of the Cervix. International Journal Of Gynecological Pathology 2014, 33: 524-530. PMID: 25083971, DOI: 10.1097/pgp.0000000000000086.Peer-Reviewed Original ResearchConceptsHuman papillomavirus (HPV) statusMicroglandular hyperplasiaSmall biopsy specimensEndometrial malignancyClinical historyBiopsy specimensHigh risk human papillomavirus statusCarcinoembryonic antigenKi-67 proliferation indexMitotic activityModerate nuclear atypiaPatient's clinical historySignet ring cellsSignificant mitotic activityReticular growth patternMicroglandular patternVimentin immunostainsPatient ageCase seriesEndocervical polypEndometrial adenocarcinomaEndocervical glandsDiagnostic dilemmaClinical prognosisMucinous differentiationRecurrent chromosomal aberrations in intravenous leiomyomatosis of the uterus: high-resolution array comparative genomic hybridization study
Buza N, Xu F, Wu W, Carr RJ, Li P, Hui P. Recurrent chromosomal aberrations in intravenous leiomyomatosis of the uterus: high-resolution array comparative genomic hybridization study. Human Pathology 2014, 45: 1885-1892. PMID: 25033729, DOI: 10.1016/j.humpath.2014.05.010.Peer-Reviewed Original ResearchConceptsOligonucleotide array comparative genomic hybridizationArray comparative genomic hybridizationComparative genomic hybridizationGenome-wide investigationGenomic hybridizationChromosome 22qCopy number lossGene mappingChromosomal aberrationsComparative genomic hybridization studySuccinate dehydrogenase subunit BGenetic instabilityRecurrent chromosomal aberrationsRegions of lossSequencing analysisChromosome 12qNumber lossNumber variantsSubunit BChromosomal alterationsHybridization studies
2010
Inverse p16 and p63 Expression in Small Cell Carcinoma and High-Grade Urothelial Cell Carcinoma of the Urinary Bladder
Buza N, Cohen PJ, Pei Hui, Parkash V. Inverse p16 and p63 Expression in Small Cell Carcinoma and High-Grade Urothelial Cell Carcinoma of the Urinary Bladder. International Journal Of Surgical Pathology 2010, 18: 94-102. PMID: 20164052, DOI: 10.1177/1066896909359914.Peer-Reviewed Original Research