2024
Uterine teratoma and the role of short-tandem repeat genotyping in understanding origins
AlAshqar A, Maruthi V, Abi-Raad R, Greenman M, Hui P, Ratner E, Altwerger G, Santin A, Andikyan V. Uterine teratoma and the role of short-tandem repeat genotyping in understanding origins. Gynecologic Oncology Reports 2024, 56: 101652. DOI: 10.1016/j.gore.2024.101652.Peer-Reviewed Original ResearchUterine teratomaPluripotent stem cellsMolecular testingRare tumorLimitations of diagnostic imagingHistory of vaginal bleedingShort tandem repeat genotypingStem cellsAdvanced molecular testingRepeat genotypingFallopian tube tissueGerm cell layersLoss of heterozygosityFour-week historyVaginal bleedingSurgical resectionOvarian counterpartRare entityUterine massPrimiparous womenEndometrial samplesFetal tissuesTeratomaPresence of tissueDiploid karyotypeRandomized phase II trial of weekly ixabepilone with or without biweekly bevacizumab for platinum-resistant or refractory ovarian/fallopian tube/primary peritoneal cancer: Updated survival and subgroup analyses
Roque D, Siegel E, Buza N, Bellone S, Huang G, Andikyan V, Clark M, Azodi M, Schwartz P, Rao G, Xu F, Hui P, Altwerger G, Ratner E, Santin A. Randomized phase II trial of weekly ixabepilone with or without biweekly bevacizumab for platinum-resistant or refractory ovarian/fallopian tube/primary peritoneal cancer: Updated survival and subgroup analyses. Gynecologic Oncology 2024, 190: s299-s301. DOI: 10.1016/j.ygyno.2024.07.449.Peer-Reviewed Original ResearchMixed Gestational Trophoblastic Tumors-Challenging Clinicopathological Presentations.
Niu N, Buza N, Hui P. Mixed Gestational Trophoblastic Tumors-Challenging Clinicopathological Presentations. International Journal Of Gynecological Pathology 2024 PMID: 38959396, DOI: 10.1097/pgp.0000000000001044.Peer-Reviewed Original ResearchPlacental site trophoblastic tumorEpithelioid trophoblastic tumorSerum human chorionic gonadotropinHuman chorionic gonadotropinTrophoblastic tumorImmune checkpoint inhibitor therapyActinomycin D therapyMethotrexate-based chemotherapyVariable clinicopathological presentationsCheckpoint inhibitor therapyGestational trophoblastic tumorsSerum hCG levelsExtrauterine metastasesMultiagent chemotherapyVaginal bleedingHCG levelsHydatidiform moleInhibitor therapyCervical massUterine massGestational originEndometrial biopsyClinicopathological presentationPatient ageDisease-freeTrastuzumab deruxtecan (DS-8201a), a HER2-targeting antibody–drug conjugate, demonstrates in vitro and in vivo antitumor activity against primary and metastatic ovarian tumors overexpressing HER2
Mutlu L, McNamara B, Bellone S, Manavella D, Demirkiran C, Greenman M, 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, demonstrates in vitro and in vivo antitumor activity against primary and metastatic ovarian tumors overexpressing HER2. Clinical & Experimental Metastasis 2024, 41: 765-775. PMID: 38909139, DOI: 10.1007/s10585-024-10297-z.Peer-Reviewed Original ResearchHigh-grade serous ovarian cancerClear cell carcinomaHER2-targeting antibody-drug conjugateAntibody-drug conjugatesT-DXdReceptor over-expressionTrastuzumab deruxtecanXenograft modelCell linesOvarian clear cell carcinomaOvarian cancer cell linesTumors overexpressing HER2Biologically aggressive tumorsFluorescence in situ hybridization assaySerous ovarian cancerEffective antibody-drug conjugatesIn vivo antitumor activityMouse xenograft modelMetastatic cell linesDS-8201aCancer cell linesAggressive tumorsHER2 expressionCell carcinomaOvarian cancerDiandric triploid partial mole versus digynic nonmolar triploidy: is morphological assessment sufficient for the diagnostic distinction?
Nagy A, Niu N, Sun T, Buza N, Hui P. Diandric triploid partial mole versus digynic nonmolar triploidy: is morphological assessment sufficient for the diagnostic distinction? Histopathology 2024, 85: 879-888. PMID: 39031756, DOI: 10.1111/his.15247.Peer-Reviewed Original ResearchPositive predictive valueTriploid gestationsPartial moleTrophoblastic hyperplasiaVillous sizeCistern formationHistological parametersPostmolar gestational trophoblastic neoplasiaTriploid partial molesGenotype-phenotype correlation studiesGestational trophoblastic neoplasiaPartial hydatidiform moleModerate interobserver agreementVillous populationsTrophoblastic neoplasiaGestational weeksHydatidiform moleClinical presentationPatient ageDigynic triploidyAbnormal histologyInterobserver agreementGestationSyncytiotrophoblastHistological assessmentTargetable ERBB2/HER2 Mutations in Gynecologic Malignancies: Clinicopathological, Immunohistochemical, and Molecular Correlations.
Manrai P, McHenry A, Sun T, Santin A, Ratner E, Lin D, Elvin J, Hui P, Buza N. Targetable ERBB2/HER2 Mutations in Gynecologic Malignancies: Clinicopathological, Immunohistochemical, and Molecular Correlations. International Journal Of Gynecological Pathology 2024 PMID: 38914011, DOI: 10.1097/pgp.0000000000001050.Peer-Reviewed Original ResearchEndometrial carcinomaGynecologic malignanciesTyrosine kinase domainHER2-mutated non-small cell lung cancerTargeted anti-HER2 therapyNon-small cell lung cancerHigh-grade endometrioid adenocarcinomasFam-trastuzumab deruxtecanOvarian mucinous adenocarcinomaAnti-HER2 therapyAnti-HER2 drugsHER2 3+US Food and Drug AdministrationCell lung cancerEndometrial serous carcinomaSolid tumor typesStandard treatment recommendationsFood and Drug AdministrationFluorescence in situ hybridizationGynecological cancer typesEndometrial primaryMullerian originSerous carcinomaHER2 IHCEndometrioid adenocarcinomaRandomized 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 vaccinationImiquimodImproving diagnostic yield of pancreatic serous cystadenoma with cyst fluid ancillary testing, adjunct immunohistochemistry, and additional fine‐needle biopsy sampling
Wang X, Zhang X, Hui P, Cai G. Improving diagnostic yield of pancreatic serous cystadenoma with cyst fluid ancillary testing, adjunct immunohistochemistry, and additional fine‐needle biopsy sampling. Cancer Cytopathology 2024, 132: 425-434. PMID: 38450993, DOI: 10.1002/cncy.22808.Peer-Reviewed Original ResearchDiagnosis of serous cystadenomaFine-needle biopsyFine-needle aspirationCyst fluid carcinoembryonic antigenPancreatic serous cystadenomaSerous cystadenomaAncillary testsCEA levelsCytological diagnosisFine-needle aspiration cell blocksFine-needle aspiration diagnosisFine-needle aspiration casesCyst fluid CEA levelsSerous cystadenoma casesFluid carcinoembryonic antigenLow CEA levelFine-needle biopsy samplingKRAS mutation analysisWild-type KRASConcurrent fine-needle aspirationImprove diagnostic yieldInhibin immunostainingAtypical cellsCytology casesDiagnostic yieldCorrection: Randomised phase II trial of weekly ixabepilone ± biweekly bevacizumab for platinum-resistant or refractory ovarian/fallopian tube/primary peritoneal cancer
Roque D, Siegel E, Buza N, Bellone S, Silasi D, Huang G, Andikyan V, Clark M, Azodi M, Schwartz P, Rao G, Reader J, Hui P, Tymon-Rosario J, Harold J, Mauricio D, Zeybek B, Menderes G, Altwerger G, Ratner E, Santin A. Correction: Randomised phase II trial of weekly ixabepilone ± biweekly bevacizumab for platinum-resistant or refractory ovarian/fallopian tube/primary peritoneal cancer. British Journal Of Cancer 2024, 130: 1073-1073. PMID: 38438590, PMCID: PMC10951353, DOI: 10.1038/s41416-024-02628-4.Peer-Reviewed Original ResearchNovel FOXL2 Mutation in an Ovarian Adult Granulosa Cell Tumor: Report of a Case With Diagnostic and Clinicopathologic Implications
Nagy A, Niu N, Ratner E, Hui P, Buza N. Novel FOXL2 Mutation in an Ovarian Adult Granulosa Cell Tumor: Report of a Case With Diagnostic and Clinicopathologic Implications. International Journal Of Gynecological Pathology 2024, 43: 631-636. PMID: 38426544, DOI: 10.1097/pgp.0000000000001024.Peer-Reviewed Original ResearchAdult granulosa cell tumorGranulosa cell tumorsOvarian sex cord-stromal tumorsSex cord-stromal tumorsCord-stromal tumorsCell tumorsFOXL2 mutationMutation c.Fibromatous stromaMalignant ovarian sex cord-stromal tumorAdjuvant vaginal cuff brachytherapyOvarian adult granulosa cell tumorsBilateral salpingo-oophorectomyRight ovarian massVaginal cuff brachytherapyAtypical endometrial hyperplasiaSuperficial myometrial invasionRoutine molecular testingUniform tumor cellsEndometrioid endometrial adenocarcinomaNested growth patternPoint mutation c.Months follow-upSalpingo-oophorectomyTotal hysterectomy
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 statusCorrigendum to “Elimusertib (BAY1895344), a novel ATR inhibitor, demonstrates in vivo activity in ATRX mutated models of uterine leiomyosarcoma”
Harold J, Bellone S, Manavell 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. Corrigendum to “Elimusertib (BAY1895344), a novel ATR inhibitor, demonstrates in vivo activity in ATRX mutated models of uterine leiomyosarcoma”. Gynecologic Oncology 2023, 170: 334. PMID: 36906375, PMCID: PMC10266020, DOI: 10.1016/j.ygyno.2023.01.029.Peer-Reviewed Original ResearchTrastuzumab 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 collaborationIntraductal papillary neoplasm of the bile duct: Cytomorphologic and molecular features
Stendahl K, Gilani SM, Basturk O, Hui P, Sigel C, Cai G. Intraductal papillary neoplasm of the bile duct: Cytomorphologic and molecular features. Cancer Cytopathology 2022, 131: 37-49. PMID: 36041224, PMCID: PMC9812877, DOI: 10.1002/cncy.22637.Peer-Reviewed Original ResearchConceptsIntraductal papillary neoplasmBile ductCytomorphologic featuresFine granular chromatinPapillary neoplasmVacuolated cytoplasmGranular chromatinCase of IPNBColumnar cellsComplex papillary architectureOriginal cytological diagnosisCommon bile ductCharacteristic cytomorphologic featuresHigh-grade dysplasiaMolecular featuresBackground mucinKRAS testingHepatic ductRetrospective studyAcute inflammationHistopathologic confirmationKRAS mutationsPapillary architecturePapillary clustersCytological diagnosisCharacteristics 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 17