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 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 status
2022
Elimusertib (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 expression
2021
Integrated mutational landscape analysis of uterine leiomyosarcomas
Choi J, Manzano A, Dong W, Bellone S, Bonazzoli E, Zammataro L, Yao X, Deshpande A, Zaidi S, Guglielmi A, Gnutti B, Nagarkatti N, Tymon-Rosario JR, Harold J, Mauricio D, Zeybek B, Menderes G, Altwerger G, Jeong K, Zhao S, Buza N, Hui P, Ravaggi A, Bignotti E, Romani C, Todeschini P, Zanotti L, Odicino F, Pecorelli S, Ardighieri L, Bilguvar K, Quick CM, Silasi DA, Huang GS, Andikyan V, Clark M, Ratner E, Azodi M, Imielinski M, Schwartz PE, Alexandrov LB, Lifton RP, Schlessinger J, Santin AD. Integrated mutational landscape analysis of uterine leiomyosarcomas. Proceedings Of The National Academy Of Sciences Of The United States Of America 2021, 118: e2025182118. PMID: 33876771, PMCID: PMC8053980, DOI: 10.1073/pnas.2025182118.Peer-Reviewed Original ResearchConceptsHomologous recombination DNA repair deficiencySequencing dataWhole-genome sequencing dataRNA sequencing dataTCGA samplesCopy number variation analysisATRX/DAXXCopy number lossNumber variation analysisDNA repair deficiencyWhole-exome sequencing dataRecurrent somatic mutationsCopy number gainsCancer Genome AtlasPatient-derived xenograftsTumor suppressorAkt geneGenetic landscapeHRD signaturesPTEN geneGenesMost fusionsC-MycMutational signaturesC-myc/
2020
Frequent 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
2019
Whole-exome sequencing of cervical carcinomas identifies activating ERBB2 and PIK3CA mutations as targets for combination therapy
Zammataro L, Lopez S, Bellone S, Pettinella F, Bonazzoli E, Perrone E, Zhao S, Menderes G, Altwerger G, Han C, Zeybek B, Bianchi A, Manzano A, Manara P, Cocco E, Buza N, Hui P, Wong S, Ravaggi A, Bignotti E, Romani C, Todeschini P, Zanotti L, Odicino F, Pecorelli S, Donzelli C, Ardighieri L, Angioli R, Raspagliesi F, Scambia G, Choi J, Dong W, Bilguvar K, Alexandrov LB, Silasi DA, Huang GS, Ratner E, Azodi M, Schwartz PE, Pirazzoli V, Stiegler AL, Boggon TJ, Lifton RP, Schlessinger J, Santin AD. Whole-exome sequencing of cervical carcinomas identifies activating ERBB2 and PIK3CA mutations as targets for combination therapy. Proceedings Of The National Academy Of Sciences Of The United States Of America 2019, 116: 22730-22736. PMID: 31624127, PMCID: PMC6842590, DOI: 10.1073/pnas.1911385116.Peer-Reviewed Original ResearchConceptsPI3K/AKT/mTOR pathwaySquamous cell carcinomaWhole-exome sequencingAKT/mTOR pathwayPrimary cervical cancer cell linesPIK3CA inhibitorsRecurrent cervical cancer patientsMTOR pathwayCombination of copanlisibCervical cancer patientsPI3K/Akt/mTORCervical cancer xenograftsRegression of tumorsCervical cancer cell linesCervical tumor cell linesSingle nucleotide variantsWild-type tumorsRecurrent somatic missense mutationsAkt/mTORCell linesPan-HERCancer cell linesTypes 16/18Cervical cancerCancer patients
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 cases