Erken evre oral kavite kanserlerinde lizil oksidazların boyun metastazı ve prognoz üzerine ilişkisinin araştırılması.
Öz
Giriş: Dudak ve dil kanserleri, yılda 377.713 yeni vakayla dünya çapında en sık görülen on altıncı malignitedir. Sigara kullanımının azalmasına, erken tanıya ve adjuvan tedavi yöntemlerindeki ilerlemelere rağmen batı toplumunda özellikle genç erişkinlerde dil kanserlerinin görülme sıklığında önemli artışlar görülmektedir. Bu çalışmada erken evre T1-T2 dil kanseri nedeniyle ameliyat edilen hastaların tümör hücrelerinde LOX ve LOXL-2 ekspresyonunun boyun metastazı ve prognoz üzerine etkisinin araştırılması amaçlandı.
Yöntem: Çalışmaya T1-T2 dil kanseri nedeniyle opere edilen 22 N(+) ve 21 N(-) olmak üzere toplam 43 hasta dahil edildi. Deneklerin parafin kesitlerinde sitoplazmik LOX ve LOXL-2 seviyeleri araştırıldı. LOX ve LOXL-2 vakalarının tümör T evresi, N evresi, nüks ve sağkalım sonuçları ile ilişkisi analiz edildi.
Bulgular: Çalışmaya T1-T2 dil kanseri nedeniyle opere edilen 22 N(+) ve 21 N(-) olmak üzere toplam 43 hasta dahil edildi. LOX ekspresyonu 16 hastada (n=43, %37,2) [12 N(+) ve 4 N(-)] ve LOXL-2 ekspresyonu ise 15 hastada (n=43, %34,8) [12N(+) ve 3 N(-)] tespit edildi. LOX ve LOXL-2 ekspresyonuna göre yapılan analizde LOX ve LOXL-2 ekspresyonunun tümör evresi T1 olan grupta T2 olanlara göre ve boyunda mestastatik lenf nodu bulunan N(+) grupta istatistiksel olarak anlamlı derecede yüksek olduğu belirlendi (p < 0,05). Neoplastik hücrelerde LOX ve LOXL-2 ekspresyonunun sitoplazmik boyanma oranı nüks olan hastalarda istatistiksel olarak anlamlı derecede yüksek bulundu (p<0.05).
Sonuç: Çalışmamızda yüksek LOX ve LOXL-2 ekspresyonunun lokal nüks, boyun lenf nodu metastazı ve sağkalım süresi üzerine istatistiksel olarak anlamlı etkisi olduğu gösterilmiştir. Çalışmamız hem hedefe yönelik yeni biyolojik ajanların geliştirilmesi hem de kişiye özel takip ve tedavi protokollerinin oluşturulması açısından araştırmacılara yol gösterecektir.
Anahtar Kelimeler
Lizil oksidaz ekspresyonu Erken evre dil kanseri Baş ve boyun kanseri
Proje Numarası
22870
Kaynakça
- Lydiatt,W.M.,Patel,S.G.,O'Sullivan,B.,Brandwein,M.S.,Ridge,J.A.,Migliacci,J.C.,...&Shah,J.P.(2017).Headandneckcancers—majorchangesintheAmericanJointCommitteeoncancereightheditioncancerstagingmanual.CA:acancerjournalforclinicians,67(2),122-137.
- Sung,H.,Ferlay,J.,Siegel,R.L.,Laversanne,M.,Soerjomataram,I.,Jemal,A.,&Bray,F.(2021).Globalcancerstatistics2020:GLOBOCANestimatesofincidenceandmortalityworldwidefor36cancersin185countries.CA:acancerjournalforclinicians,71(3),209-249.
- GlobalCancerObservatory.https://gco.iarc.fr/(accessedmay11,2022).
- Ettinger,K.S.,Ganry,L.,&Fernandes,R.P.(2019).Oralcavitycancer.OralandMaxillofacialSurgeryClinics,31(1),13-29.
- Goldenberg,D.,Ardekian,L.,Rachmiel,A.,Peled,M.,Joachims,H.Z.,&Laufer,D.(2000).Carcinomaofthedorsumofthetongue.Head&Neck:JournalfortheSciencesandSpecialtiesoftheHeadandNeck,22(2),190-194.ISO690
- Calabrese,L.,Giugliano,G.,Bruschini,R.,Ansarin,M.,Navach,V.,Grosso,E.,...&Chiesa,F.(2009).Compartmentalsurgeryintonguetumours:descriptionofanewsurgicaltechnique.ActaOtorhinolaryngologicaItalica,29(5),259.ISO690
- Yuen,A.P.W.,Wei,W.I.,Wong,Y.M.,&Tang,K.C.(1997).Electiveneckdissectionversusobservationinthetreatmentofearlyoraltonguecarcinoma.Head&Neck:JournalfortheSciencesandSpecialtiesoftheHeadandNeck,19(7),583-588.ISO690
- AbuGhanem,S.,Yehuda,M.,Carmel,N.N.,Leshno,M.,Abergel,A.,Gutfeld,O.,&Fliss,D.M.(2016).Electiveneckdissectionvsobservationinearly-stagesquamouscellcarcinomaoftheoraltonguewithnoclinicallyapparentlymphnodemetastasisintheneck:asystematicreviewandmeta-analysis.JAMAOtolaryngology–Head&NeckSurgery,142(9),857-865.
- HusseinAA,HelderMN,deVisscherJG,etal.Globalincidenceoforalandoropharynxcancerinpatientsyoungerthan45yearsversusolderpatients:asystematicreview.EurJCancer.2017;82:115-127.
- SatgunaseelanL,AllansonBM,AsherR,etal.Theincidenceofsquamouscellcarcinomaoftheoraltongueisrisinginyoungnon-smokingwomen:aninternationalmulti-institutionalanalysis.OralOncol.2020;110:104875.
- KamaliA,GahmC,PalmgrenB,MarklundL,HalleM,Hammarstedt-NordenvallL.RegionalrecurrenceinearlystageI-IIoraltonguecancer:asingleinstitutionalstudyandreviewoftheliterature.ActaOtolaryngol.2017Jul;137(7):755-761.doi:10.1080/00016489.2017.1279751.Epub2017Feb22.PMID:28361597.
- LeQT,DenkoNC,GiacciaAJ:Hypoxicgeneexpressionandmetastasis.CancerMetastasisRev23:293-310,2004
- ErlerJT,BennewithKL,NicolauM,etal:Lysyloxidaseisessentialforhypoxia-inducedmetastasis.Nature440:1222-1226,2006
- KirschmannDA,SeftorEA,FongSF,NievaDR,SullivanCM,EdwardsEM,SommerP,CsiszarK,HendrixMJ.Amolecularroleforlysyloxidaseinbreastcancerinvasion.CancerRes2002;62:4478–83.
- Lee,Y.S.,Park,Y.,Kwon,M.,Roh,J.L.,Choi,S.H.,Nam,S.Y.,&Kim,S.Y.(2017).Expressionoflysyloxidasepredictiveofdistantmetastasisoflaryngealcancer.Otolaryngology–headandnecksurgery,156(3),489-497.ISO690
- Sanada,T.,Islam,A.,Kaminota,T.,Kirino,Y.,Tanimoto,R.,Yoshimitsu,H.,...&Hato,N.(2020).Elevatedexosomallysyloxidaselike2isapotentialbiomarkerforheadandnecksquamouscellcarcinoma.TheLaryngoscope,130(5),E327-E334.
- GilkesDM,SemenzaGL,WirtzD.Hypoxiaandtheextracellularmatrix:driversoftumourmetastasis.NatRevCancer.2014;14:430-439.
- LuceroH,KaganH.Lysyloxidase:anoxidativeenzymeandeffectorofcellfunction.CellMolLifeSci.2006;63:2304-2316.
- ErlerJT,BennewithKL,NicolauM,etal.Lysyloxidaseisessentialforhypoxia-inducedmetastasis.Nature.2006;440:1222-1226.
- Albinger‐Hegyi,A.,Stoeckli,S.J.,Schmid,S.,Storz,M.,Iotzova,G.,Probst‐Hensch,N.M.,...&Hegyi,I.(2010).Lysyloxidaseexpressionisanindependentmarkerofprognosisandapredictoroflymphnodemetastasisinoralandoropharyngealsquamouscellcarcinoma(OSCC).Internationaljournalofcancer,126(11),2653-2662.
- J.J.Cruz,A.Ocana,E.DelBarco,etal.Targeting receptor tyrosine kinases and their signal transduction routes in head and neck cancer Ann. Oncol., 18 (3) (2007), pp. 421-430
- Sanada,T.,Islam,A.,Kaminota,T.,Kirino,Y.,Tanimoto,R.,Yoshimitsu,H.,...&Hato,N.(2020).Elevatedexosomallysyloxidaselike2isapotentialbiomarkerforheadandnecksquamouscellcarcinoma.TheLaryngoscope,130(5),E327-E334.
Investigation of the relationship of lysyl oxidases on neck metastasis and prognosis in early stage oral cavity cancers.
Öz
Introduction: Cancers of the lip and tongue are the sixteenth most common malignancy worldwide, with 377,713 new cases per year. Despite the decrease in smoking, early diagnosis, and advances in adjuvant treatment methods, significant increases in tongue cancers incidence are observed in western society, especially in young adults. This study aims to investigate the effect of LOX and LOXL-2 expression in tumor cells of patients operated on for early-stage T1-T2 tongue cancer on neck metastasis and prognosis.
Methods: A total of 43 patients, 22 N(+) and 21 N(-) operated for T1-T2 tongue cancer were included in the study. He sought to discover cytoplasmic level LOX and LOXL-2 in the paraffin sections of subjects. The relationship of LOX and LOXL-2 cases with tumor T stage, N stage, recurrence, and survival outcomes were analyzed.
Results: A total of 43 patients, 22 N(+) and 21 N(-) operated for T1-T2 tongue cancer were included in the study. LOX expression was observed in 16 patients (n=43, 37.2%) (12 N(+) and 4 N(-)) and in 15 patients (n=43, 34.8%) (12N(+) and 3 N(-) )) LOXL-2 expression was detected. In the analysis performed according to LOX and LOXL-2 expression, it was determined that LOX and LOXL-2 expression was statistically significantly higher in the group with tumor stage T1 than in those with T2 and in the N(+) group with pathological lymph nodes in the neck compared to those with N(-) (p <0.05).
The cytoplasmic staining rate of LOX and LOXL-2 expression in neoplastic cells was found to be statistically significantly higher in patients with recurrence (p <0.05).
Conclusion: In our study, high LOX and LOXL-2 expression has been shown to have a statistically significant effect on regional recurrence, neck lymph node metastasis, and survival time. Our study will guide researchers in terms of both the development of new targeted biological agents and the creation of individualized follow-up and treatment protocols.
Anahtar Kelimeler
Lysyl oxidase expression Early stage tongue cancer Head and neck cancer
Destekleyen Kurum
Ege Üniversitesi Bilimsel Araştırma Projeleri Koordinatörlüğü
Proje Numarası
22870
Kaynakça
- Lydiatt,W.M.,Patel,S.G.,O'Sullivan,B.,Brandwein,M.S.,Ridge,J.A.,Migliacci,J.C.,...&Shah,J.P.(2017).Headandneckcancers—majorchangesintheAmericanJointCommitteeoncancereightheditioncancerstagingmanual.CA:acancerjournalforclinicians,67(2),122-137.
- Sung,H.,Ferlay,J.,Siegel,R.L.,Laversanne,M.,Soerjomataram,I.,Jemal,A.,&Bray,F.(2021).Globalcancerstatistics2020:GLOBOCANestimatesofincidenceandmortalityworldwidefor36cancersin185countries.CA:acancerjournalforclinicians,71(3),209-249.
- GlobalCancerObservatory.https://gco.iarc.fr/(accessedmay11,2022).
- Ettinger,K.S.,Ganry,L.,&Fernandes,R.P.(2019).Oralcavitycancer.OralandMaxillofacialSurgeryClinics,31(1),13-29.
- Goldenberg,D.,Ardekian,L.,Rachmiel,A.,Peled,M.,Joachims,H.Z.,&Laufer,D.(2000).Carcinomaofthedorsumofthetongue.Head&Neck:JournalfortheSciencesandSpecialtiesoftheHeadandNeck,22(2),190-194.ISO690
- Calabrese,L.,Giugliano,G.,Bruschini,R.,Ansarin,M.,Navach,V.,Grosso,E.,...&Chiesa,F.(2009).Compartmentalsurgeryintonguetumours:descriptionofanewsurgicaltechnique.ActaOtorhinolaryngologicaItalica,29(5),259.ISO690
- Yuen,A.P.W.,Wei,W.I.,Wong,Y.M.,&Tang,K.C.(1997).Electiveneckdissectionversusobservationinthetreatmentofearlyoraltonguecarcinoma.Head&Neck:JournalfortheSciencesandSpecialtiesoftheHeadandNeck,19(7),583-588.ISO690
- AbuGhanem,S.,Yehuda,M.,Carmel,N.N.,Leshno,M.,Abergel,A.,Gutfeld,O.,&Fliss,D.M.(2016).Electiveneckdissectionvsobservationinearly-stagesquamouscellcarcinomaoftheoraltonguewithnoclinicallyapparentlymphnodemetastasisintheneck:asystematicreviewandmeta-analysis.JAMAOtolaryngology–Head&NeckSurgery,142(9),857-865.
- HusseinAA,HelderMN,deVisscherJG,etal.Globalincidenceoforalandoropharynxcancerinpatientsyoungerthan45yearsversusolderpatients:asystematicreview.EurJCancer.2017;82:115-127.
- SatgunaseelanL,AllansonBM,AsherR,etal.Theincidenceofsquamouscellcarcinomaoftheoraltongueisrisinginyoungnon-smokingwomen:aninternationalmulti-institutionalanalysis.OralOncol.2020;110:104875.
- KamaliA,GahmC,PalmgrenB,MarklundL,HalleM,Hammarstedt-NordenvallL.RegionalrecurrenceinearlystageI-IIoraltonguecancer:asingleinstitutionalstudyandreviewoftheliterature.ActaOtolaryngol.2017Jul;137(7):755-761.doi:10.1080/00016489.2017.1279751.Epub2017Feb22.PMID:28361597.
- LeQT,DenkoNC,GiacciaAJ:Hypoxicgeneexpressionandmetastasis.CancerMetastasisRev23:293-310,2004
- ErlerJT,BennewithKL,NicolauM,etal:Lysyloxidaseisessentialforhypoxia-inducedmetastasis.Nature440:1222-1226,2006
- KirschmannDA,SeftorEA,FongSF,NievaDR,SullivanCM,EdwardsEM,SommerP,CsiszarK,HendrixMJ.Amolecularroleforlysyloxidaseinbreastcancerinvasion.CancerRes2002;62:4478–83.
- Lee,Y.S.,Park,Y.,Kwon,M.,Roh,J.L.,Choi,S.H.,Nam,S.Y.,&Kim,S.Y.(2017).Expressionoflysyloxidasepredictiveofdistantmetastasisoflaryngealcancer.Otolaryngology–headandnecksurgery,156(3),489-497.ISO690
- Sanada,T.,Islam,A.,Kaminota,T.,Kirino,Y.,Tanimoto,R.,Yoshimitsu,H.,...&Hato,N.(2020).Elevatedexosomallysyloxidaselike2isapotentialbiomarkerforheadandnecksquamouscellcarcinoma.TheLaryngoscope,130(5),E327-E334.
- GilkesDM,SemenzaGL,WirtzD.Hypoxiaandtheextracellularmatrix:driversoftumourmetastasis.NatRevCancer.2014;14:430-439.
- LuceroH,KaganH.Lysyloxidase:anoxidativeenzymeandeffectorofcellfunction.CellMolLifeSci.2006;63:2304-2316.
- ErlerJT,BennewithKL,NicolauM,etal.Lysyloxidaseisessentialforhypoxia-inducedmetastasis.Nature.2006;440:1222-1226.
- Albinger‐Hegyi,A.,Stoeckli,S.J.,Schmid,S.,Storz,M.,Iotzova,G.,Probst‐Hensch,N.M.,...&Hegyi,I.(2010).Lysyloxidaseexpressionisanindependentmarkerofprognosisandapredictoroflymphnodemetastasisinoralandoropharyngealsquamouscellcarcinoma(OSCC).Internationaljournalofcancer,126(11),2653-2662.
- J.J.Cruz,A.Ocana,E.DelBarco,etal.Targeting receptor tyrosine kinases and their signal transduction routes in head and neck cancer Ann. Oncol., 18 (3) (2007), pp. 421-430
- Sanada,T.,Islam,A.,Kaminota,T.,Kirino,Y.,Tanimoto,R.,Yoshimitsu,H.,...&Hato,N.(2020).Elevatedexosomallysyloxidaselike2isapotentialbiomarkerforheadandnecksquamouscellcarcinoma.TheLaryngoscope,130(5),E327-E334.
Ayrıntılar
| Birincil Dil | İngilizce |
|---|---|
| Konular | Kulak Burun Boğaz |
| Bölüm | Araştırma Makaleleri |
| Yazarlar | |
| Proje Numarası | 22870 |
| Yayımlanma Tarihi | 8 Eylül 2025 |
| Gönderilme Tarihi | 28 Ocak 2025 |
| Kabul Tarihi | 24 Nisan 2025 |
| Yayımlandığı Sayı | Yıl 2025 Cilt: 64 Sayı: 3 |
