2024
Targetable 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 adenocarcinoma
2023
Preliminary results of a phase II trial with sacituzumab govitecan-hziy in patients with recurrent endometrial carcinoma overexpressing Trop-2.
Santin A, McNamara B, Siegel E, Harold J, Mutlu L, Altwerger G, Huang G, Andikyan V, Clark M, Ratner E, Azodi M, Dottino P, Schwartz P, Bellone S. Preliminary results of a phase II trial with sacituzumab govitecan-hziy in patients with recurrent endometrial carcinoma overexpressing Trop-2. Journal Of Clinical Oncology 2023, 41: 5599-5599. DOI: 10.1200/jco.2023.41.16_suppl.5599.Peer-Reviewed Original ResearchRecurrent endometrial carcinomaSacituzumab govitecan-hziyTrop-2 overexpressionPhase 2 trialEndometrial carcinomaUterine serous carcinomaTrop-2Endometrioid adenocarcinomaSerous carcinomaClinical activityMetastatic triple-negative breast cancerAnti-Trop-2 antibodyGrade 3 endometrioid adenocarcinomaTriple-negative breast cancerAdequate bone marrowUnexpected safety signalsMetastatic urothelial cancerClear cell histologyPhase II trialSystemic corticosteroid usePlatinum-based chemotherapyFavorable safety profileDurable disease controlRemarkable clinical activityStage 1
2022
Distinct Mechanisms of Mismatch-Repair Deficiency Delineate Two Modes of Response to Anti-PD-1 Immunotherapy in Endometrial Carcinoma.
Chow RD, Michaels T, Bellone S, Hartwich T, Bonazzoli E, Iwasaki A, Song E, Santin AD. Distinct Mechanisms of Mismatch-Repair Deficiency Delineate Two Modes of Response to Anti-PD-1 Immunotherapy in Endometrial Carcinoma. Cancer Discovery 2022, 13: 312-331. PMID: 36301137, PMCID: PMC9905265, DOI: 10.1158/2159-8290.cd-22-0686.Peer-Reviewed Original ResearchConceptsAnti-PD-1 immunotherapyImmune checkpoint blockadeMMRd tumorsNK cellsEndometrial carcinomaICB responseMutation burdenT-cell-driven immunityPhase II clinical trialMMRd endometrial cancersPD-1 inhibitorsMismatch repair-deficient cancersTumor-extrinsic factorsHigh response rateEffector CD8Antitumor immunityEndometrial cancerCancer immunotherapyImmune cellsLonger survivalClinical trialsPrimary resistanceT cellsResponse rateMMRdBiomarker associations of immune checkpoint inhibitor versus chemotherapy effectiveness in first-line metastatic endometrial carcinomas: A real-world study.
Santin A, Graf R, Shah K, Kelly A, Danziger N, Lin D, Oxnard G, Elvin J. Biomarker associations of immune checkpoint inhibitor versus chemotherapy effectiveness in first-line metastatic endometrial carcinomas: A real-world study. Journal Of Clinical Oncology 2022, 40: 5596-5596. DOI: 10.1200/jco.2022.40.16_suppl.5596.Peer-Reviewed Original ResearchSingle-agent immune checkpoint inhibitorsImmune checkpoint inhibitorsTumor mutational burdenCheckpoint inhibitorsMEC patientsChemotherapy effectivenessMSI statusAnti-PD1 immune checkpoint inhibitorsFirst-line immune checkpoint inhibitorsMultivariable Cox proportional hazards modelsCox proportional hazards modelMetastatic endometrial carcinomaOverall survival comparisonEndometrial carcinoma patientsMut/MbProportional hazards modelReal-world studyPrespecified analysis planHazard ratioStandard chemotherapyCarcinoma patientsEndometrial carcinomaPredictive biomarkersChemotherapy treatmentFavorable outcomeLenvatinib Plus Pembrolizumab for Advanced Endometrial Cancer
Makker V, Colombo N, Herráez A, Santin A, Colomba E, Miller D, Fujiwara K, Pignata S, Baron-Hay S, Ray-Coquard I, Shapira-Frommer R, Ushijima K, Sakata J, Yonemori K, Kim Y, Guerra E, Sanli U, McCormack M, Smith A, Keefe S, Bird S, Dutta L, Orlowski R, Lorusso D. Lenvatinib Plus Pembrolizumab for Advanced Endometrial Cancer. Obstetrical & Gynecological Survey 2022, 77: 275-276. DOI: 10.1097/ogx.0000000000001032.Peer-Reviewed Original ResearchEndometrial cancerRecurrent endometrial cancerSecond-line treatmentAdvanced endometrial cancerPlatinum-based chemotherapyRecurrent endometrial carcinomaTyrosine kinase inhibitorsEndometrial carcinomaOptimal treatmentDisease progressionLimited efficacySingle agentKinase inhibitorsLenvatinibCancerTreatmentPembrolizumabLittle consensusChemotherapyCarcinomaProgression
2021
145 Characterization of adverse reactions in patients with advanced endometrial cancer (aec) receiving lenvatinib + pembrolizumab (Study 309/KEYNOTE-775)
Colombo N, Lorusso D, Santin A, Kim Y, Herráez A, Yonemori K, Fujiwara K, Colomba E, Miller D, Pignata S, Monk B, Guerra E, Kristeleit R, Orlando M, Sanli U, Dutta L, Orlowski R, Ren M, Makker V. 145 Characterization of adverse reactions in patients with advanced endometrial cancer (aec) receiving lenvatinib + pembrolizumab (Study 309/KEYNOTE-775). International Journal Of Gynecological Cancer 2021, 31: a78-a78. DOI: 10.1136/ijgc-2021-esgo.120.Peer-Reviewed Original ResearchPalmar-plantar erythrodysesthesiaLenvatinib dose reductionAdverse reactionsMusculoskeletal painDose reductionPrior platinum-based therapyAEC patientsTarget lesion diametersCommon adverse reactionsAdvanced endometrial cancerManagement of patientsPlatinum-based therapyQd poEndometrial cancerTreatment initiationMedian timeEndometrial carcinomaHypertensionLenvatinibPrompt identificationPhysician's choiceDiarrheaPatientsFirst onsetMeaningful improvements
2018
Endometrial Carcinoma in a 26-Year-Old Patient with Bardet-Biedl Syndrome
Grechukhina O, Gressel GM, Munday W, Wong S, Santin A, Vash-Margita A. Endometrial Carcinoma in a 26-Year-Old Patient with Bardet-Biedl Syndrome. Case Reports In Obstetrics And Gynecology 2018, 2018: 1952351. PMID: 29854508, PMCID: PMC5960523, DOI: 10.1155/2018/1952351.Peer-Reviewed Original ResearchAbnormal uterine bleedingBardet-Biedl syndromeEndometrial cancerUterine bleedingRisk factorsDefinitive surgical treatmentIndependent risk factorEndometrioid endometrial adenocarcinomaRare genetic conditionOvulatory dysfunctionBilateral salpingectomyCentral obesityOlder patientsTruncal obesityYounger patientsEndometrioid adenocarcinomaSurgical treatmentEndometrial adenocarcinomaEndometrial carcinomaClinical signsCognitive impairmentPatientsCancerGenetic conditionsBleeding
2016
Regression of Chemotherapy-Resistant Polymerase ϵ (POLE) Ultra-Mutated and MSH6 Hyper-Mutated Endometrial Tumors with Nivolumab
Santin AD, Bellone S, Buza N, Choi J, Schwartz PE, Schlessinger J, Lifton RP. Regression of Chemotherapy-Resistant Polymerase ϵ (POLE) Ultra-Mutated and MSH6 Hyper-Mutated Endometrial Tumors with Nivolumab. Clinical Cancer Research 2016, 22: 5682-5687. PMID: 27486176, PMCID: PMC5135588, DOI: 10.1158/1078-0432.ccr-16-1031.Peer-Reviewed Original ResearchConceptsImmune checkpoint inhibitor nivolumabCheckpoint inhibitor nivolumabClinical responseInhibitor nivolumabAnti-PD-1 inhibitorsHyper-mutated tumorsPatient's clinical responseRemarkable clinical responsesAlternative therapeutic optionNovel treatment optionsRecurrent/metastaticHigh side effectsRecurrent diseaseEndometrial carcinomaTherapeutic optionsTreatment optionsModern chemotherapyGrade 3Side effectsPatientsHuman tumorsTumorsGene mutationsNivolumabChemotherapy
2015
Polymerase ε (POLE) ultra-mutated tumors induce robust tumor-specific CD4+ T cell responses in endometrial cancer patients
Bellone S, Centritto F, Black J, Schwab C, English D, Cocco E, Lopez S, Bonazzoli E, Predolini F, Ferrari F, Silasi DA, Ratner E, Azodi M, Schwartz PE, Santin AD. Polymerase ε (POLE) ultra-mutated tumors induce robust tumor-specific CD4+ T cell responses in endometrial cancer patients. Gynecologic Oncology 2015, 138: 11-17. PMID: 25931171, PMCID: PMC4469551, DOI: 10.1016/j.ygyno.2015.04.027.Peer-Reviewed Original ResearchConceptsCytotoxic T lymphocytesCancer patientsPole tumorsT cellsHigher IFN-γ expressionLevels of CD8Endometrial cancer patientsTumor-specific CD4T cell responsesEndometrial cancer cellsIFN-γ expressionHelper armCTL responsesEndometrial cancerFavorable prognosisBetter prognosisEndometrial carcinomaLymphoid subsetsNaïve CD4T lymphocytesTumor extractsCD4CD8Immune systemCell responses
2014
FIGO 2008 staging for endometrial cancer
English D, Santin A. FIGO 2008 staging for endometrial cancer. 2014, 82-96. DOI: 10.2217/fmeb2013.13.115.Peer-Reviewed Original ResearchFIGO staging systemEndometrial cancer patientsStaging systemEndometrial cancerCancer patientsCervical glandular involvementFIGO stage 1AObstetrics (FIGO) staging systemPositive peritoneal cytologySurgical staging systemClinical staging systemPeritoneal cytologySurgical stagingClinicopathologic studyOverall survivalGlandular involvementPathologic findingsEndometrial carcinomaDisease stageSignificant changesStage 1ACurrent evidenceInvolved nodesAssignment of stageCancerHER2/neu in Endometrial Cancer: A Promising Therapeutic Target With Diagnostic Challenges
Buza N, Roque DM, Santin AD. HER2/neu in Endometrial Cancer: A Promising Therapeutic Target With Diagnostic Challenges. Archives Of Pathology & Laboratory Medicine 2014, 138: 343-50. PMID: 24576030, DOI: 10.5858/arpa.2012-0416-ra.Peer-Reviewed Original ResearchConceptsEndometrial carcinomaHER2/neuPromising therapeutic targetHER2 testingClinical responseTherapeutic targetHumanized monoclonal immunoglobulin G1 antibodyMonoclonal immunoglobulin G1 antibodyUterine serous carcinomaImmunoglobulin G1 antibodyNovel therapeutic strategiesEndometrial cancerSerous adenocarcinomaSerous carcinomaCase reportDiagnostic challengeHER2 overexpressionPathogenetic featuresClinical studiesG1 antibodyTherapeutic strategiesCarcinomaTherapeutic efficacyStandardized criteriaTherapy
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
2012
Trop-2 protein overexpression is an independent marker for predicting disease recurrence in endometrioid endometrial carcinoma
Bignotti E, Zanotti L, Calza S, Falchetti M, Lonardi S, Ravaggi A, Romani C, Todeschini P, Bandiera E, Tassi RA, Facchetti F, Sartori E, Pecorelli S, Roque DM, Santin AD. Trop-2 protein overexpression is an independent marker for predicting disease recurrence in endometrioid endometrial carcinoma. BMC Clinical Pathology 2012, 12: 22. PMID: 23151048, PMCID: PMC3534488, DOI: 10.1186/1472-6890-12-22.Peer-Reviewed Original ResearchDisease-free survivalEndometrioid endometrial carcinomaTrop-2 overexpressionProgression-free survivalIndependent prognostic factorHigh tumor gradePrognostic factorsEndometrial carcinomaTumor gradeMultivariate analysisTrop-2 protein expressionPoor disease-free survivalReduced disease-free survivalProtein expressionAdvanced FIGO stageCommon gynecologic malignancyEndometrioid endometrial cancerLymphovascular space invasionProtein overexpressionParaffin-embedded specimensAggressive tumor phenotypeSurgical stagingCervical involvementMedical comorbiditiesEndometrial cancerTargeted therapy for high-risk endometrial carcinoma
Roque D, Schwartz P, Santin A. Targeted therapy for high-risk endometrial carcinoma. Journal Of Clinical Practice 2012, 9: 539-554. DOI: 10.2217/cpr.12.44.Peer-Reviewed Original ResearchType II endometrial cancerEndometrial cancerHigh-risk endometrial carcinomaHigh-risk cancerAggressive clinical courseRational therapeutic strategiesMolecular pathway alterationsClinical courseEndometrial carcinomaPoor prognosisClinical behaviorDisease burdenTargeted therapyTherapeutic strategiesSmall molecule inhibitorsClinical advancesPathway alterationsDistinct histopathologyCytotoxic agentsCancerCurrent standardImmunotherapyMolecular characterizationCarcinomaPrognosis
2010
Letter to the Editor referring to the manuscript entitled: “Phase II trial of trastuzumab in women with advanced or recurrent HER-positive endometrial carcinoma: a Gynecologic Oncology Group study” recently reported by Fleming et al., (Gynecol Oncol., 116;15–20;2010)
Santin AD. Letter to the Editor referring to the manuscript entitled: “Phase II trial of trastuzumab in women with advanced or recurrent HER-positive endometrial carcinoma: a Gynecologic Oncology Group study” recently reported by Fleming et al., (Gynecol Oncol., 116;15–20;2010). Gynecologic Oncology 2010, 118: 95-96. PMID: 20172595, DOI: 10.1016/j.ygyno.2010.01.043.Peer-Reviewed Original Research
2008
Trefoil factor 3: a novel serum marker identified by gene expression profiling in high-grade endometrial carcinomas
Bignotti E, Ravaggi A, Tassi RA, Calza S, Rossi E, Falchetti M, Romani C, Bandiera E, Odicino FE, Pecorelli S, Santin AD. Trefoil factor 3: a novel serum marker identified by gene expression profiling in high-grade endometrial carcinomas. British Journal Of Cancer 2008, 99: 768-773. PMID: 18682706, PMCID: PMC2528153, DOI: 10.1038/sj.bjc.6604546.Peer-Reviewed Original ResearchConceptsTrefoil factor 3Novel serum markerG3 EECSerum markersEndometrial carcinomaHigh-grade endometrial carcinomasEndometrial hyperplasia patientsEndometrioid endometrial carcinomaEndometrial hyperplasiaSerum levelsHyperplasia patientsHealthy patientsSerum concentrationsQuantitative real-time PCRHealthy controlsReal-time PCREndometrium biopsyTFF3 expressionPatientsTFF3 proteinEarly detectionGene expression profilingProtein levelsQRT-PCRExpression levelsTrastuzumab treatment in patients with advanced or recurrent endometrial carcinoma overexpressing HER2/neu
Santin AD, Bellone S, Roman JJ, McKenney JK, Pecorelli S. Trastuzumab treatment in patients with advanced or recurrent endometrial carcinoma overexpressing HER2/neu. International Journal Of Gynecology & Obstetrics 2008, 102: 128-131. PMID: 18555254, DOI: 10.1016/j.ijgo.2008.04.008.Peer-Reviewed Original ResearchMeSH KeywordsAgedAntibodies, MonoclonalAntibodies, Monoclonal, HumanizedAntineoplastic AgentsCA-125 AntigenDisease ProgressionEndometrial NeoplasmsFemaleGene Expression Regulation, NeoplasticGenes, erbB-2HumansImmunohistochemistryIn Situ Hybridization, FluorescenceNeoplasm Recurrence, LocalReceptor, ErbB-2TrastuzumabConceptsMetastatic endometrial carcinomaHER2/neuEndometrial carcinomaSingle agentCA-125 evaluationHER2/neu receptorRecurrent metastatic diseaseRecurrent endometrial carcinomaEffect of trastuzumabSerial CT scansViable therapeutic optionC-erbB2 gene amplificationSalvage chemotherapyClinical responseMetastatic diseaseTrastuzumab treatmentTherapeutic optionsStudy criteriaDisease progressionCT scanPatientsTrastuzumabNeu receptorChemotherapyRadiation treatmentRecurrent endometrial carcinoma regression with the use of the aromatase inhibitor anastrozole
Bellone S, Shah HR, McKenney JK, Stone PJ, Santin AD. Recurrent endometrial carcinoma regression with the use of the aromatase inhibitor anastrozole. American Journal Of Obstetrics And Gynecology 2008, 199: e7-e10. PMID: 18550023, DOI: 10.1016/j.ajog.2008.04.012.Peer-Reviewed Original Research
2005
Amplification of c‐erbB2 oncogene
Santin AD, Bellone S, Van Stedum S, Bushen W, Palmieri M, Siegel ER, De Las Casas LE, Roman JJ, Burnett A, Pecorelli S. Amplification of c‐erbB2 oncogene. Cancer 2005, 104: 1391-1397. PMID: 16116605, DOI: 10.1002/cncr.21308.Peer-Reviewed Original ResearchMeSH KeywordsAge FactorsAgedBiomarkers, TumorBiopsy, NeedleCystadenocarcinoma, PapillaryFemaleGene AmplificationGene Expression Regulation, NeoplasticGenes, erbB-2HumansImmunohistochemistryIn Situ Hybridization, FluorescenceMiddle AgedProbabilityPrognosisReceptor, ErbB-2Risk AssessmentSampling StudiesSensitivity and SpecificityStatistics, NonparametricSurvival AnalysisUterine NeoplasmsConceptsNeu gene amplificationHER-2/neu geneEndometrial carcinomaGene amplificationSerous papillary endometrial carcinomaTumor cellsHER-2/neuNeu genePapillary endometrial carcinomaKaplan-Meier curvesImportant prognostic indicatorAfrican American patientsDisease-related deathLog-rank testShorter survival timeFISH-negative patientsNovel treatment strategiesC patientsSame tumor samplesAggressive variantPatient survivalPoor outcomePoor prognosisPrognostic indicatorClinical managementHigh serum levels of interleukin-6 in endometrial carcinoma are associated with uterine serous papillary histology, a highly aggressive and chemotherapy-resistant variant of endometrial cancer
Bellone S, Watts K, Cane' S, Palmieri M, Cannon MJ, Burnett A, Roman JJ, Pecorelli S, Santin AD. High serum levels of interleukin-6 in endometrial carcinoma are associated with uterine serous papillary histology, a highly aggressive and chemotherapy-resistant variant of endometrial cancer. Gynecologic Oncology 2005, 98: 92-98. PMID: 15904949, DOI: 10.1016/j.ygyno.2005.03.016.Peer-Reviewed Original ResearchConceptsUterine serous papillary carcinomaIL-6 gene expression levelsEndometrioid carcinomaInterleukin-6Primary endometrioid carcinomaEnzyme-linked immunosorbent assayEndometrial carcinomaHealthy femalesUSPC patientsMean serum IL-6 levelPrimary USPC cell linesIL-6 serum concentrationsSerum IL-6 levelsAnti-tumor immune functionBenign abdominal diseasesChemotherapy-resistant variantsControl endometrial cellsNormal healthy femalesSerous papillary histologyUSPC cell linesIL-6 concentrationsIL-6 levelsBenign disease patientsHigher serum levelsSerous papillary carcinoma