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
2023
TP53 Mutation-driven Stratified Mucin-producing Carcinoma Coexisting With Squamous Cell Carcinoma of the Vulva: A Case Study
Wadia R, McHenry A, Abi-Raad R, Hui P. TP53 Mutation-driven Stratified Mucin-producing Carcinoma Coexisting With Squamous Cell Carcinoma of the Vulva: A Case Study. International Journal Of Gynecological Pathology 2023, 42: 555-560. PMID: 37255422, DOI: 10.1097/pgp.0000000000000961.Peer-Reviewed Original ResearchConceptsSquamous cell carcinomaInvasive squamous cell carcinomaVulvar intraepithelial neoplasiaCell carcinomaIntraepithelial neoplasiaLichen sclerosusAssociated with high-risk human papillomavirus infectionHigh-risk human papillomavirus infectionDifferentiated vulvar intraepithelial neoplasiaPresence of lymphovascular invasionInguinal lymph node metastasisHuman papillomavirus infectionVulvar lichen sclerosusMucin-producing carcinomaLymph node metastasisIntraepithelial lesionsLymphovascular invasionTP53 mutationsNode metastasisPapillomavirus infectionNeoplastic componentsCarcinomaUnique caseTP53SclerosusKRAS 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 ResearchConceptsOvarian 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 statusTrastuzumab deruxtecan (DS-8201a), a HER2-targeting antibody–drug conjugate with topoisomerase I inhibitor payload, shows antitumor activity in uterine and ovarian carcinosarcoma with HER2/neu expression
Mauricio D, Bellone S, Mutlu L, McNamara B, Manavella D, Demirkiran C, Verzosa M, Buza N, Hui P, Hartwich T, Harold J, Yang-Hartwich Y, Zipponi M, Altwerger G, Ratner E, Huang G, Clark M, Andikyan V, Azodi M, Schwartz P, Santin A. Trastuzumab deruxtecan (DS-8201a), a HER2-targeting antibody–drug conjugate with topoisomerase I inhibitor payload, shows antitumor activity in uterine and ovarian carcinosarcoma with HER2/neu expression. Gynecologic Oncology 2023, 170: 38-45. PMID: 36610380, PMCID: PMC10445234, DOI: 10.1016/j.ygyno.2022.12.018.Peer-Reviewed Original ResearchConceptsHER2/neu expressionDS-8201aAntibody-drug conjugatesNeu expressionCS cell linesTrastuzumab deruxtecanOvarian carcinosarcomaTopoisomerase I inhibitor payloadCell linesAggressive gynecologic malignancyLimited therapeutic optionsEffective antibody-drug conjugatesCarcinosarcoma cell lineGynecologic malignanciesTherapeutic optionsIsotype controlSarcomatous elementsXenograft modelBystander killingFlow cytometryTumor cellsCarcinosarcomaAntitumor activityVivo studiesVivo activity
2022
Ovarian and uterine carcinosarcomas are sensitive in vitro and in vivo to elimusertib, a novel ataxia-telangiectasia and Rad3-related (ATR) kinase inhibitor
Manavella D, McNamara B, Harold J, Bellone S, Hartwich T, Yang-Hartwich Y, Mutlu L, Zipponi M, Demirkiran C, Verzosa M, Altwerger G, Ratner E, Huang G, Clark M, Andikyan V, Azodi M, Schwartz P, Dottino P, Choi J, Alexandrov L, Buza N, Hui P, Santin A. Ovarian and uterine carcinosarcomas are sensitive in vitro and in vivo to elimusertib, a novel ataxia-telangiectasia and Rad3-related (ATR) kinase inhibitor. Gynecologic Oncology 2022, 169: 98-105. PMID: 36525930, PMCID: PMC9925406, DOI: 10.1016/j.ygyno.2022.12.003.Peer-Reviewed Original ResearchConceptsHomologous recombination deficiencyCS cell linesCell linesWestern blotKinase inhibitorsOverall animal survivalProtein expressionDose-dependent increaseDose-dependent inhibitionCarcinosarcoma cell lineTumor growth inhibitionCaspase-3 expressionEndometrioid histologyAggressive malignancyUterine carcinosarcomaCS patientsPreclinical activityClinical trialsEpithelial componentAnimal survivalXenograftsApoptosis markersRecombination deficiencyP-ATRP-Chk1Elimusertib (BAY1895344), a novel ATR inhibitor, demonstrates in vivo activity in ATRX mutated models of uterine leiomyosarcoma
Harold J, Bellone S, Manavella D, Mutlu L, McNamara B, Hartwich T, Zipponi M, Yang-Hartwich Y, Demirkiran C, Verzosa M, Choi J, Dong W, Buza N, Hui P, Altwerger G, Huang G, Andikyan V, Clark M, Ratner E, Azodi M, Schwartz P, Santin A. Elimusertib (BAY1895344), a novel ATR inhibitor, demonstrates in vivo activity in ATRX mutated models of uterine leiomyosarcoma. Gynecologic Oncology 2022, 168: 157-165. PMID: 36442427, PMCID: PMC9797429, DOI: 10.1016/j.ygyno.2022.11.014.Peer-Reviewed Original ResearchConceptsPatient-derived xenograftsUterine leiomyosarcomaVivo activityVehicle control treatmentMedian overall survivalTumor volume differencesOral scheduleWestern blot analysisOverall survivalOral gavageAggressive malignancyPDX modelsClinical trialsSCID miceTumor measurementsULMS patientsSignificant growth inhibitionNovel ATR inhibitorTumor samplesSignificant toxicityWestern blotKinase inhibitorsATRX mutationsGene mutationsControl vehicleCorrelative Assessment of p53 Immunostaining Patterns and TP53 Mutation Status by Next-Generation Sequencing in High-Grade Endometrial Carcinomas
Matsumoto N, Manrai P, Rottmann D, Wu X, Assem H, Hui P, Buza N. Correlative Assessment of p53 Immunostaining Patterns and TP53 Mutation Status by Next-Generation Sequencing in High-Grade Endometrial Carcinomas. International Journal Of Gynecological Pathology 2022, 42: 567-575. PMID: 36730675, DOI: 10.1097/pgp.0000000000000930.Peer-Reviewed Original ResearchConceptsHigh-grade endometrial carcinomasEndometrial carcinomaEndometrioid endometrial carcinomaTP53 mutation statusP53 immunohistochemistrySerous componentIHC staining patternNext-generation sequencing resultsNuclear overexpressionGrade 3 endometrioid endometrial carcinomaMutation statusTP53 mutationsCytoplasmic stainingStaining patternSerous endometrial carcinomaAberrant p53 expressionMixed endometrial carcinomasClinical prognosisSurrogate markerAberrant p53 proteinTherapeutic decisionsIHC patternsTP53 alterationsTumor histotypesP53 expressionDataset for the Reporting of Gestational Trophoblastic Neoplasia: Recommendations From the International Collaboration on Cancer Reporting (ICCR)
Hui P, Webster F, Baergen RN, Buza N, Cheung ANY, Kaur B, Ronnett BM, Shih IM, Seckl MJ, Lax SF, McCluggage WG. Dataset for the Reporting of Gestational Trophoblastic Neoplasia: Recommendations From the International Collaboration on Cancer Reporting (ICCR). International Journal Of Gynecological Pathology 2022, 41: s34-s43. PMID: 36305533, DOI: 10.1097/pgp.0000000000000876.Peer-Reviewed Original ResearchConceptsGestational trophoblastic neoplasiaTrophoblastic neoplasiaCancer reportingPathologic parametersTumor stagingCancer sitesPathology reportsPatient managementPatient careNeoplasiaNoncore elementsStagingTumor classificationPathologyInternational expertsDifferent populationsReportingCancer datasetsInternational collaborationCharacteristics 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 agentCOVID-19 & differential effects in twins: Insights from Placenta Pathology
Moriarty K, Yu M, Hussain N, Zgutka K, Sanders MM, Harigopal M, Wang J, Wang X, Hui P, Liu C, Sink D, Shields A. COVID-19 & differential effects in twins: Insights from Placenta Pathology. Placenta 2022, 124: 62-66. PMID: 35640456, PMCID: PMC9121647, DOI: 10.1016/j.placenta.2022.05.014.Peer-Reviewed Original ResearchConceptsSARS-CoV-2Perinatal lossCOVID-19Adverse pregnancy outcomesMaternal-fetal interfaceTime of infectionDifferential effectsPregnancy outcomesPremature deliveryFetal interfaceGestational agePlacenta pathologyTwin pregnanciesMembranous expressionFemale fetusesFetal sexViral detection methodsViral receptorsFemale twinsTissue resultsPregnancyPlacentaTask ForceSuccumbedFetusesRandomised phase II trial of weekly ixabepilone ± biweekly bevacizumab for platinum-resistant or refractory ovarian/fallopian tube/primary peritoneal cancer
Roque DM, Siegel ER, Buza N, Bellone S, Silasi DA, Huang GS, Andikyan V, Clark M, Azodi M, Schwartz PE, Rao GG, Reader JC, Hui P, Tymon-Rosario JR, Harold J, Mauricio D, Zeybek B, Menderes G, Altwerger G, Ratner E, Santin AD. Randomised phase II trial of weekly ixabepilone ± biweekly bevacizumab for platinum-resistant or refractory ovarian/fallopian tube/primary peritoneal cancer. British Journal Of Cancer 2022, 126: 1695-1703. PMID: 35149854, PMCID: PMC8853032, DOI: 10.1038/s41416-022-01717-6.Peer-Reviewed Original ResearchConceptsPrimary peritoneal cancerPeritoneal cancerPredictive biomarkersDay 1Taxane-resistant ovarian cancerPhase II trialM2 days 1Bevacizumab 10Evaluable patientsPrior bevacizumabWeekly ixabepiloneII trialPrimary endpointSecondary endpointsRefractory statusTUBB3 expressionPrior receiptSubgroup analysisClinical trialsOvarian cancerIxabepilonePFSCancerBevacizumabPatients
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 MSIProgression of Cystadenoma to Mucinous Borderline Ovarian Tumor in Young Females: Case Series and Literature Review
Beroukhim G, Ozgediz D, Cohen PJ, Hui P, Morotti R, Schwartz PE, Yang-Hartwich, Vash-Margita A. Progression of Cystadenoma to Mucinous Borderline Ovarian Tumor in Young Females: Case Series and Literature Review. Journal Of Pediatric And Adolescent Gynecology 2021, 35: 359-367. PMID: 34843973, DOI: 10.1016/j.jpag.2021.11.003.Peer-Reviewed Original ResearchConceptsMucinous borderline ovarian tumorsBorderline ovarian tumorsOvarian tumorsYale-New Haven HospitalRetrospective chart reviewBenign ovarian tumorsBenign ovarian lesionsRate of recurrenceNew Haven HospitalAbdominal painPreoperative characteristicsChart reviewDisease recurrenceRecurrent cystsCase seriesChief complaintClinical presentationClinicopathologic featuresFemale patientsMucinous cystadenomaOvarian cystsOvarian lesionsTumor stageAdolescent patientsSubsequent surveillanceA Timely Update of Immunohistochemistry and Molecular Classification in the Diagnosis and Risk Assessment of Endometrial Carcinomas.
Wang M, Hui P. A Timely Update of Immunohistochemistry and Molecular Classification in the Diagnosis and Risk Assessment of Endometrial Carcinomas. Archives Of Pathology & Laboratory Medicine 2021, 145: 1367-1378. PMID: 34673912, DOI: 10.5858/arpa.2021-0098-ra.Peer-Reviewed Original ResearchBiomarkers, TumorCarcinomaDNA Copy Number VariationsDNA Polymerase IIEndometrial NeoplasmsFemaleGene DosageHumansImmunohistochemistryMicrosatellite InstabilityMolecular Diagnostic TechniquesMutationPoly-ADP-Ribose Binding ProteinsPredictive Value of TestsPrognosisTerminology as TopicTumor Suppressor Protein p53Increased Detection of Mycobacterium tuberculosis Disease Using a Tissue-Based Laboratory-Developed Polymerase Chain Reaction Assay Compared to Standard Diagnostics.
Mackow NA, Abi-Raad R, Kerantzas CA, Hui P, Malinis M, Azar MM. Increased Detection of Mycobacterium tuberculosis Disease Using a Tissue-Based Laboratory-Developed Polymerase Chain Reaction Assay Compared to Standard Diagnostics. American Journal Of Tropical Medicine And Hygiene 2021, 105: 1657-1661. PMID: 34544041, PMCID: PMC8641361, DOI: 10.4269/ajtmh.21-0104.Peer-Reviewed Original ResearchMeSH KeywordsAdultAgedCulture TechniquesFemaleHumansLungLymph NodesMaleMiddle AgedMycobacterium tuberculosisPleuraReal-Time Polymerase Chain ReactionReference StandardsRetrospective StudiesSensitivity and SpecificitySputumTuberculosisTuberculosis, Lymph NodeTuberculosis, Multidrug-ResistantTuberculosis, PleuralTuberculosis, PulmonaryConceptsComposite reference standardMTB PCRAFB cultureMycobacterium tuberculosisPolymerase chain reactionAcid-fast bacilli smearMycobacterium tuberculosis diseasePositive AFB cultureChain reactionReal-time polymerase chain reactionStandard diagnosticsBacilli smearMTB casesTuberculosis diseaseClinical sensitivityLong turnaround timeXpertClinical performanceReference standardPCRVariable sensitivityTurnaround timeLymphPatientsTuberculosisMinimal 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 ResearchConceptsMinimal 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 seriesImmunohistochemical and molecular pathological typing in the differential diagnosis and prognosis risk assessment of endometrial carcinoma
Wang M, Hui P. Immunohistochemical and molecular pathological typing in the differential diagnosis and prognosis risk assessment of endometrial carcinoma. 中华病理学杂志 2021, 50: 1078-1082. PMID: 34496509, DOI: 10.3760/cma.j.cn112151-20210628-00463.Peer-Reviewed Original ResearchDHES0815A, 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
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 types