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1、ClinicalSignificanceofCellCycle–andApoptosis-RelatedMarkersinBiliaryTractCancerCholangiocarcinomaisthesecondmostcommonprimaryhepatictumor,anditsincidenceisincreasing.Preventionofthiscancerisverydifficult,andonlyafewriskfactorshavebeensofaridentified.Cholangiocarcinoma
2、arisesfromthebiliaryepithelialcellsandcanoccuranywherealongthebiliarytract.Tumorsaredividedanatomicallyintointrahepaticandextrahepaticcholangiocarcinomas,aswellasadenocarcinomasofthegallbladder.Despitetheirsimilarmorphologicfeatures,differenceshavebeenfoundamongtheses
3、ubtypesinrelationtotheirclinicalcourse,geneticprofiles,andimmunophenotypes.MaterialsandMethodsMaterialsandMethodsFormalin-fixedandparaffin-embeddedtumorandcontrolspecimenswereretrievedfromthearchivesoftheInstituteofPathology,UniversityofBern,Bern,Switzerland.Alltumora
4、ndcontrolspecimenswerereviewedbyonepathologist(E.K.)..TheTMAconsistedof128cholangiocarcinomacasesincluding42intrahepaticand70extrahepaticcholangiocarcinomasand16gallbladdercarcinomas,aswellas29normalcontrolsamples.The128patientscomprised70menand58womenwithamean±SDageo
5、f64±2years(range,30-90years).AssessmentofBehaviorMedicalchartswereavailablefor57(44.5%)of128patients.Ofthese57patients,45(79%)diedofthedisease,and6(11%)werealivewithrecurrentormetastaticdisease.Anadditional6patients(11%)werealivewithoutdisease.Themedianfollow-upwas11.
6、5months(mean±SD,21.05±4.9months;range,0-108months).ImmunohistochemicalStainingTheTMAsectionswereusedforimmunohistochemicalstainingwith7differentantibodies.TheprimaryantibodiesandtheirdilutionsarelistedinTable1.ImmunohistochemicalStaining.Theprimaryantibodywasomittedfo
7、rnegativecontrolexperiments.Forapositivecontrolexperiment,aTMAwithvariousnormaltissuesampleswasstainedinparallel.Nuclearimmunoreactivityforp53,p16,p21,andp27wasvisuallyscored.Acasewasconsideredpositiveifimmunoreactivitywasdetectedinatleast10%ofthetumorcellnuclei,onthe
8、basisofpreviousreports.Onlyforp27,thecutoffwas50%ofpositivetumorcellnuclei.Forbcl-2andbax,staininginmorethan10%oftumorcellsw
