2024
An algorithm for standardization of tumor Infiltrating lymphocyte evaluation in head and neck cancers
Xirou V, Moutafi M, Bai Y, Nwe Aung T, Burela S, Liu M, Kimple R, Shabbir Ahmed F, Schultz B, Flieder D, Connolly D, Psyrri A, Burtness B, Rimm D. An algorithm for standardization of tumor Infiltrating lymphocyte evaluation in head and neck cancers. Oral Oncology 2024, 152: 106750. PMID: 38547779, PMCID: PMC11060915, DOI: 10.1016/j.oraloncology.2024.106750.Peer-Reviewed Original ResearchMeSH KeywordsAgedAlgorithmsFemaleHead and Neck NeoplasmsHumansLymphocytes, Tumor-InfiltratingMaleMiddle AgedPrognosisRetrospective StudiesConceptsTumor-infiltrating lymphocytesHead and neck cancerTILs evaluationHPV-positiveNeck cancerPrognostic valueHead and neck squamous cell cancer casesTIL variablesAssociated with favorable prognosisHPV-negative headHPV-negative populationHematoxylin-eosin-stained sectionsCox regression analysisPotential clinical implicationsInter-observer variabilityInfiltrating lymphocytesClinicopathological factorsFavorable prognosisValidation cohortTumor cellsCancer casesProspective settingQuPath softwareRetrospective collectionPredictive significance
2023
Emerging Prognostic and Predictive Significance of Stress Keratin 17 in HPV-Associated and Non HPV-Associated Human Cancers: A Scoping Review
Lozar T, Wang W, Gavrielatou N, Christensen L, Lambert P, Harari P, Rimm D, Burtness B, Kuhar C, Carchman E. Emerging Prognostic and Predictive Significance of Stress Keratin 17 in HPV-Associated and Non HPV-Associated Human Cancers: A Scoping Review. Viruses 2023, 15: 2320. PMID: 38140561, PMCID: PMC10748233, DOI: 10.3390/v15122320.Peer-Reviewed Original ResearchConceptsSquamous cell carcinomaTriple-negative breast cancerCancer typesPredictive significancePrognostic factorsClinical outcomesPrognostic significanceCell carcinomaHuman cancersCervical squamous cell carcinomaNeck squamous cell carcinomaAvailable clinical evidenceCochrane Central RegisterInferior clinical outcomesPositive prognostic factorNegative predictive factorNegative prognostic factorWeb of ScienceCentral RegisterControlled TrialsCervical cancerClinical evidencePredictive factorsPancreatic cancerEligible studiesDigital spatial profiling links beta-2-microglobulin expression with immune checkpoint blockade outcomes in head and neck squamous cell carcinoma
Gavrielatou N, Vathiotis I, Aung T, Shafi S, Burela S, Fernandez A, Moutafi M, Burtness B, Economopoulou P, Anastasiou M, Foukas P, Psyrri A, Rimm D. Digital spatial profiling links beta-2-microglobulin expression with immune checkpoint blockade outcomes in head and neck squamous cell carcinoma. Cancer Research Communications 2023, 3: 558-563. PMID: 37057033, PMCID: PMC10088911, DOI: 10.1158/2767-9764.crc-22-0299.Peer-Reviewed Original ResearchMeSH KeywordsCarcinomaHead and Neck NeoplasmsHumansImmune Checkpoint InhibitorsNeoplasm Recurrence, LocalSquamous Cell Carcinoma of Head and NeckConceptsDigital spatial profilingB2M expressionOverall survivalM HNSCCImmunotherapy outcomesNeck squamous cell carcinoma (HNSCC) treatmentHigh beta-2 microglobulinSquamous cell carcinoma treatmentCell death protein 1Neck squamous cell carcinomaM expressionPretreatment biopsy samplesImmune checkpoint inhibitorsPD-L1 expressionImmune checkpoint markersDeath protein 1Squamous cell carcinomaB2MBeta-2-microglobulinBeta 2 microglobulin expressionImproved PFSCheckpoint inhibitorsMetastatic headCheckpoint markersImproved survival
2022
Quantitative assessment of Siglec-15 expression in lung, breast, head, and neck squamous cell carcinoma and bladder cancer.
Shafi S, Aung T, Xirou V, Gavrielatou N, Vathiotis I, Fernandez A, Moutafi M, Yaghoobi V, Herbst R, Liu L, Langermann S, Rimm D. Quantitative assessment of Siglec-15 expression in lung, breast, head, and neck squamous cell carcinoma and bladder cancer. Laboratory Investigation 2022, 102: 1143-1149. PMID: 36775354, DOI: 10.1038/s41374-022-00796-6.Peer-Reviewed Original ResearchConceptsSiglec-15 expressionNon-small cell lung cancerNeck squamous cell carcinomaProgression-free survivalSquamous cell carcinomaCancer typesOverall survivalCell carcinomaBladder cancerImmune cellsSiglec-15PD-1/PD-L1 blockadePotential future clinical trialsQuantitative immunofluorescencePD-L1 blockadeStromal immune cellsImmune checkpoint blockadeCell lung cancerFuture clinical trialsNew potential targetsCheckpoint blockadePD-L1Lung cancerClinical trialsIntra-tumoral heterogeneity
2021
PARP inhibitors in head and neck cancer: Molecular mechanisms, preclinical and clinical data
Moutafi M, Economopoulou P, Rimm D, Psyrri A. PARP inhibitors in head and neck cancer: Molecular mechanisms, preclinical and clinical data. Oral Oncology 2021, 117: 105292. PMID: 33862558, DOI: 10.1016/j.oraloncology.2021.105292.Peer-Reviewed Original ResearchConceptsPoly (ADP-ribose) polymerase (PARP) inhibitorsCheckpoint inhibitorsCell death 1 (PD-1) checkpoint inhibitorsDeath-1 checkpoint inhibitorsDeath ligand 1 (PD-L1) expressionPARP inhibitorsPD-1 checkpoint inhibitorsNeck squamous cell carcinomaCornerstone of treatmentLigand 1 expressionImmune modulating effectsSquamous cell carcinomaSuccessful treatment outcomeDesign of trialsOutcome of therapyTreatment landscapeCell carcinomaNeck cancerTreatment outcomesClinical dataTherapeutic strategiesDNA damageRecent approvalImmune primingNucleotide excision repair
2018
Utility of CD8 score by automated quantitative image analysis in head and neck squamous cell carcinoma
Hartman DJ, Ahmad F, Ferris R, Rimm D, Pantanowitz L. Utility of CD8 score by automated quantitative image analysis in head and neck squamous cell carcinoma. Oral Oncology 2018, 86: 278-287. PMID: 30409313, PMCID: PMC6260977, DOI: 10.1016/j.oraloncology.2018.10.005.Peer-Reviewed Original ResearchConceptsCD8 T cellsImmune cell densityOropharyngeal HNSCCT cellsNeck squamous cell carcinomaCD8 cell densityImmune cell infiltratesSquamous cell carcinomaWhole tissue sectionsEntire tumor sectionHPV infectionMedian survivalCell infiltrateHNSCC patientsCell carcinomaHNSCC casesClinicopathologic parametersOnly predictorTumor sectionsBetter outcomesClinical practiceTumor microenvironmentCell densityClinical validationCells/
2017
Assessing Tumor-Infiltrating Lymphocytes in Solid Tumors
Hendry S, Salgado R, Gevaert T, Russell PA, John T, Thapa B, Christie M, van de Vijver K, Estrada MV, Gonzalez-Ericsson PI, Sanders M, Solomon B, Solinas C, Van den Eynden GGGM, Allory Y, Preusser M, Hainfellner J, Pruneri G, Vingiani A, Demaria S, Symmans F, Nuciforo P, Comerma L, Thompson EA, Lakhani S, Kim SR, Schnitt S, Colpaert C, Sotiriou C, Scherer SJ, Ignatiadis M, Badve S, Pierce RH, Viale G, Sirtaine N, Penault-Llorca F, Sugie T, Fineberg S, Paik S, Srinivasan A, Richardson A, Wang Y, Chmielik E, Brock J, Johnson DB, Balko J, Wienert S, Bossuyt V, Michiels S, Ternes N, Burchardi N, Luen SJ, Savas P, Klauschen F, Watson PH, Nelson BH, Criscitiello C, O’Toole S, Larsimont D, de Wind R, Curigliano G, André F, Lacroix-Triki M, van de Vijver M, Rojo F, Floris G, Bedri S, Sparano J, Rimm D, Nielsen T, Kos Z, Hewitt S, Singh B, Farshid G, Loibl S, Allison KH, Tung N, Adams S, Willard-Gallo K, Horlings HM, Gandhi L, Moreira A, Hirsch F, Dieci MV, Urbanowicz M, Brcic I, Korski K, Gaire F, Koeppen H, Lo A, Giltnane J, Rebelatto MC, Steele KE, Zha J, Emancipator K, Juco JW, Denkert C, Reis-Filho J, Loi S, Fox SB. Assessing Tumor-Infiltrating Lymphocytes in Solid Tumors. Advances In Anatomic Pathology 2017, 24: 311-335. PMID: 28777143, PMCID: PMC5638696, DOI: 10.1097/pap.0000000000000161.Peer-Reviewed Original ResearchMeSH KeywordsBiomarkers, TumorBiopsyBrain NeoplasmsCarcinoma, Non-Small-Cell LungCarcinoma, Squamous CellEndometrial NeoplasmsFemaleGastrointestinal NeoplasmsHead and Neck NeoplasmsHumansImmunohistochemistryLung NeoplasmsLymphocytes, Tumor-InfiltratingMelanomaMesotheliomaOvarian NeoplasmsPathologyPhenotypePredictive Value of TestsSkin NeoplasmsSquamous Cell Carcinoma of Head and NeckUrogenital NeoplasmsConceptsTumor-infiltrating lymphocytesDifferent tumor typesSolid tumorsTumor typesTIL assessmentImmune responsePrimary brain tumorsCommon solid tumorsInvasive breast carcinomaRoutine clinical biomarkersWorking Group guidelinesPrognostic implicationsBreast carcinomaGroup guidelinesGynecologic systemGastrointestinal tractSimple biomarkerBrain tumorsGenitourinary systemPredictive valueClinical biomarkersStandardized methodologyTumorsAvailable evidenceImmunotherapyErbB activation signatures as potential biomarkers for anti-ErbB3 treatment in HNSCC
Alvarado D, Ligon GF, Lillquist JS, Seibel SB, Wallweber G, Neumeister VM, Rimm DL, McMahon G, LaVallee TM. ErbB activation signatures as potential biomarkers for anti-ErbB3 treatment in HNSCC. PLOS ONE 2017, 12: e0181356. PMID: 28723928, PMCID: PMC5517012, DOI: 10.1371/journal.pone.0181356.Peer-Reviewed Original ResearchConceptsNeuregulin-1NRG1 expressionErbB3 activationNeck squamous cell carcinomaSquamous cell carcinomaEnhanced anti-tumor activitySubset of HNSCCUnmet medical needHNSCC cell linesHNSCC patient samplesAnti-tumor activityGrowth factor αLigand neuregulin-1Cell carcinomaEGFR/ErbB familyHNSCC modelsCetuximab treatmentErbB receptor inhibitionReceptor inhibitionReceptor levelsRespective signaling pathwaysSolid tumorsTumor typesHNSCCPotential biomarkers
2014
Induction cetuximab, paclitaxel, and carboplatin followed by chemoradiation with cetuximab, paclitaxel, and carboplatin for stage III/IV head and neck squamous cancer: a phase II ECOG-ACRIN trial (E2303)
Wanebo HJ, Lee J, Burtness BA, Ridge JA, Ghebremichael M, Spencer SA, Psyrri D, Pectasides E, Rimm D, Rosen FR, Hancock MR, Tolba KA, Forastiere AA. Induction cetuximab, paclitaxel, and carboplatin followed by chemoradiation with cetuximab, paclitaxel, and carboplatin for stage III/IV head and neck squamous cancer: a phase II ECOG-ACRIN trial (E2303). Annals Of Oncology 2014, 25: 2036-2041. PMID: 25009013, PMCID: PMC4176450, DOI: 10.1093/annonc/mdu248.Peer-Reviewed Original ResearchConceptsEvent-free survivalStage III/IV headResponse/survivalInduction therapyComplete responseStage III/IV HNSCCNeck squamous cell carcinomaPrimary site biopsiesTreatment-related deathsPathologic complete responseNeck squamous cancerSquamous cell carcinomaProtein expression statusEligible patientsSite biopsiesOverall survivalCell carcinomaPromising survivalSquamous cancerDisease progressionChemoradiationRadiation therapyPatientsWeek 9CetuximabPrognostic Biomarkers in Phase II Trial of Cetuximab-Containing Induction and Chemoradiation in Resectable HNSCC: Eastern Cooperative Oncology Group E2303
Psyrri A, Lee JW, Pectasides E, Vassilakopoulou M, Kosmidis EK, Burtness BA, Rimm DL, Wanebo HJ, Forastiere AA. Prognostic Biomarkers in Phase II Trial of Cetuximab-Containing Induction and Chemoradiation in Resectable HNSCC: Eastern Cooperative Oncology Group E2303. Clinical Cancer Research 2014, 20: 3023-3032. PMID: 24700741, PMCID: PMC4049169, DOI: 10.1158/1078-0432.ccr-14-0113.Peer-Reviewed Original ResearchMeSH KeywordsAdultAgedAntibodies, Monoclonal, HumanizedAntineoplastic Combined Chemotherapy ProtocolsBiomarkers, TumorCarboplatinCarcinoma, Squamous CellCetuximabChemoradiotherapyDisease-Free SurvivalDrug Resistance, NeoplasmFemaleFluorescent Antibody TechniqueHead and Neck NeoplasmsHumansInduction ChemotherapyKaplan-Meier EstimateMaleMiddle AgedMitogen-Activated Protein Kinase KinasesPaclitaxelPhosphatidylinositol 3-KinasesPrognosisProportional Hazards ModelsProto-Oncogene Proteins c-aktRas ProteinsSignal TransductionSquamous Cell Carcinoma of Head and NeckTissue Array AnalysisConceptsProgression-free survivalEvent-free survivalPhase II trialOverall survivalII trialTissue microarrayStage III/IV headMultivariable Cox proportional hazards modelsMultivariable Cox regression analysisNeck squamous cell cancerRAS/MAPK/ERKCox proportional hazards modelInsulin-like growth factor 1 receptorLarge prospective studiesCox regression analysisInferior overall survivalKaplan-Meier methodSquamous cell cancerLog-rank testGrowth factor 1 receptorProportional hazards modelPI3K/Akt pathwayFactor 1 receptorPI3K/AktEGF receptorMarkers of Epithelial to Mesenchymal Transition in Association with Survival in Head and Neck Squamous Cell Carcinoma (HNSCC)
Pectasides E, Rampias T, Sasaki C, Perisanidis C, Kouloulias V, Burtness B, Zaramboukas T, Rimm D, Fountzilas G, Psyrri A. Markers of Epithelial to Mesenchymal Transition in Association with Survival in Head and Neck Squamous Cell Carcinoma (HNSCC). PLOS ONE 2014, 9: e94273. PMID: 24722213, PMCID: PMC3983114, DOI: 10.1371/journal.pone.0094273.Peer-Reviewed Original ResearchMeSH KeywordsAutomationBiomarkers, TumorCarcinoma, Squamous CellCohort StudiesEpithelial-Mesenchymal TransitionFemaleGene Expression ProfilingGene Expression Regulation, NeoplasticHead and Neck NeoplasmsHumansImage Processing, Computer-AssistedImmunohistochemistryKaplan-Meier EstimateMaleMultivariate AnalysisNeoplasm MetastasisPhenotypePrognosisProportional Hazards ModelsSquamous Cell Carcinoma of Head and NeckTreatment OutcomeConceptsProgression-free survivalSquamous cell carcinomaOverall survivalCell carcinomaE-cadherinPrimary squamous cell carcinomaNeck squamous cell carcinomaHigh-risk HNSCCKaplan-Meier analysisNovel therapeutic approachesMesenchymal transition phenotypeHigh metastatic potentialLow E-cadherinImproved OSInferior OSIndependent predictorsPoor prognosisCarcinoma prognosisClinicopathological parametersInclusion criteriaTherapeutic approachesTransition phenotypeMetastatic potentialMesenchymal transitionProtein expression analysis
2013
Molecular profile of head and neck squamous cell carcinomas bearing p16 high phenotype
Rampias T, Pectasides E, Prasad M, Sasaki C, Gouveris P, Dimou A, Kountourakis P, Perisanidis C, Burtness B, Zaramboukas T, Rimm D, Fountzilas G, Psyrri A. Molecular profile of head and neck squamous cell carcinomas bearing p16 high phenotype. Annals Of Oncology 2013, 24: 2124-2131. PMID: 23406730, DOI: 10.1093/annonc/mdt013.Peer-Reviewed Original ResearchMeSH KeywordsBeta CateninBiomarkers, TumorCarcinoma, Squamous CellCell Line, TumorCyclin-Dependent Kinase Inhibitor p16ErbB ReceptorsFemaleHead and Neck NeoplasmsHumansMaleNeoplasm ProteinsOncogene Proteins, ViralOropharyngeal NeoplasmsPapillomavirus E7 ProteinsPapillomavirus InfectionsPhosphorylationPTEN PhosphohydrolaseRepressor ProteinsRNA InterferenceRNA, Small InterferingSquamous Cell Carcinoma of Head and NeckTumor Suppressor Protein p53Wnt Signaling PathwayConceptsE6/E7Β-cateninHNSCC cellsTissue microarrayE6/E7 repressionEpidermal growth factor receptor (EGFR) pathwayNeck squamous cell cancerE6/E7 genesOropharyngeal cancer cellsNeck squamous cell carcinomaShort hairpin RNAGrowth factor receptor pathwayHPV16 E6/E7Squamous cell cancerSquamous cell carcinomaExpression of biomarkersExpression differencesPTEN upregulationAberrant EGFRE7 repressionHairpin RNAMedian OSOverall survivalPhosphorylated EGFRCell cancer
2011
Comparative Prognostic Value of Epidermal Growth Factor Quantitative Protein Expression Compared with FISH for Head and Neck Squamous Cell Carcinoma
Pectasides E, Rampias T, Kountourakis P, Sasaki C, Kowalski D, Fountzilas G, Zaramboukas T, Rimm D, Burtness B, Psyrri A. Comparative Prognostic Value of Epidermal Growth Factor Quantitative Protein Expression Compared with FISH for Head and Neck Squamous Cell Carcinoma. Clinical Cancer Research 2011, 17: 2947-2954. PMID: 21355076, DOI: 10.1158/1078-0432.ccr-10-2040.Peer-Reviewed Original ResearchCarcinomaCarcinoma, Squamous CellEpidermal Growth FactorFemaleGene DosageGene Expression Regulation, NeoplasticHead and Neck NeoplasmsHumansIn Situ Hybridization, FluorescenceMaleNeoplasms, Squamous CellPredictive Value of TestsPrognosisProteinsSquamous Cell Carcinoma of Head and NeckSurvival AnalysisTissue Array Analysis
2010
Nuclear Localization of Signal Transducer and Activator of Transcription 3 in Head and Neck Squamous Cell Carcinoma Is Associated with a Better Prognosis
Pectasides E, Egloff AM, Sasaki C, Kountourakis P, Burtness B, Fountzilas G, Dafni U, Zaramboukas T, Rampias T, Rimm D, Grandis J, Psyrri A. Nuclear Localization of Signal Transducer and Activator of Transcription 3 in Head and Neck Squamous Cell Carcinoma Is Associated with a Better Prognosis. Clinical Cancer Research 2010, 16: 2427-2434. PMID: 20371693, PMCID: PMC3030188, DOI: 10.1158/1078-0432.ccr-09-2658.Peer-Reviewed Original ResearchConceptsLonger progression-free survivalNeck squamous cell cancerNeck squamous cell carcinomaProgression-free survivalSquamous cell cancerSquamous cell carcinomaPittsburgh Medical CenterTranscription 3Early Detection Research NetworkCurative intentPrognostic roleSurgical resectionBetter prognosisSignal transducerCell cancerCell carcinomaFavorable outcomeSurvival prognosisClinicopathologic parametersMedical CenterIndependent cohortLower riskTest cohortHNSCCSurvival analysis
2005
β-Catenin Functions Mainly as an Adhesion Molecule in Patients with Squamous Cell Cancer of the Head and Neck
Yu Z, Weinberger PM, Provost E, Haffty BG, Sasaki C, Joe J, Camp RL, Rimm DL, Psyrri A. β-Catenin Functions Mainly as an Adhesion Molecule in Patients with Squamous Cell Cancer of the Head and Neck. Clinical Cancer Research 2005, 11: 2471-2477. PMID: 15814622, DOI: 10.1158/1078-0432.ccr-04-2199.Peer-Reviewed Original ResearchConceptsSquamous cell cancerCyclin D1 levelsCell cancerNeck squamous cell cancerAdhesion moleculesD1 levelsDisease-free survivalIndependent prognostic factorLocal recurrence rateKaplan-Meier analysisMembranous expression patternLow cyclin D1Cancer tissue microarrayIncidence of mutationsProtein expression levelsMean followHazard ratioPrognostic factorsLocal recurrencePathologic dataCox regressionRecurrence rateMetastasis stageTissue microarrayBeta-catenin expression
2003
Frequent alterations of Smad signaling in human head and neck squamous cell carcinomas: a tissue microarray analysis.
Xie W, Bharathy S, Kim D, Haffty BG, Rimm DL, Reiss M. Frequent alterations of Smad signaling in human head and neck squamous cell carcinomas: a tissue microarray analysis. Oncology Research Featuring Preclinical And Clinical Cancer Therapeutics 2003, 14: 61-73. PMID: 14649540, DOI: 10.3727/000000003108748612.Peer-Reviewed Original ResearchConceptsNeck squamous cell carcinomaSquamous cell carcinomaCell carcinomaHNSCC specimensTGF-beta type II receptorTGF-beta/Smad signalingTissue microarray analysisTGF-beta/SmadProgression of HNSCCCell linesType II receptorHuman SCC linesDistant recurrenceTGF-beta signalingFrequent cancerCell cycle arrestPatient outcomesMetastatic spreadTissue microarrayHNSCCII receptorsSmall seriesEvidence of lossSCC linesActivation of Smad
2001
Novel inactivating mutations of transforming growth factor‐β type I receptor gene in head‐and‐neck cancer metastases
Chen T, Yan W, Wells R, Rimm D, McNiff J, Leffell D, Reiss M. Novel inactivating mutations of transforming growth factor‐β type I receptor gene in head‐and‐neck cancer metastases. International Journal Of Cancer 2001, 93: 653-661. PMID: 11477574, DOI: 10.1002/ijc.1381.Peer-Reviewed Original ResearchMeSH KeywordsActivin Receptors, Type IAmino Acid SequenceDisease ProgressionEndoplasmic ReticulumFemaleHead and Neck NeoplasmsHumansMaleMolecular Sequence DataMutationNeoplasms, Glandular and EpithelialNeoplasms, Unknown PrimaryProtein Serine-Threonine KinasesReceptor, Transforming Growth Factor-beta Type IReceptors, Transforming Growth Factor betaSequence Homology, Amino AcidSignal TransductionTransforming Growth Factor betaConceptsT beta RNeck cancer metastasisTGF-beta signalingCancer metastasisBeta RTGF betaBeta signalingLate-stage diseaseHuman epithelial neoplasmsCorresponding primary tumorsBreast cancer metastasisFine needle aspiratesTGF-beta type I receptorNovel inactivating mutationsBeta type I receptorType I receptorStage diseaseCarcinoma cell linesPrimary tumorCell cycle arrestEpithelial neoplasmsCodon 387MetastasisI receptorHuman tumors