DistinctWNT/β-cateninsignalingactivationintheserratedneoplasiapathwayandtheadenoma-carcinomasequenceofthecolorectum.
结直肠锯齿状肿瘤通路和腺瘤-癌途径中不同的WNT/β-catenin信号激活
文献作者MurakamiT,MitomiH,SaitoT,TakahashiM,SakamotoN,FukuiN,YaoT,WatanabeS
文献译者张晓阳医院病理科
文献目录ModernPathology；Jan;28(1):2-:-58
摘要平坦锯齿状腺瘤/息肉（SSP/P）是导致结直肠癌发生的锯齿状肿瘤通路的一种早期前驱病变。传统的腺瘤-癌途径与WNT信号通路激活有关，但该通路在锯齿状病变中的作用仍存争议。为了澄清WNT信号激活与MLH1甲基化或BRAF/KRAS突变在锯齿状或传统通路中的区别，我们进行β-catenin免疫染色，甲基化特异性PCR检测MLH1和WNT信号相关基因如AXIN2，APC和MCC及分泌性卷曲相关蛋白（SFRPs）；并且对27例SSA/Ps，14例SSA/Ps伴高级别异型增生，9例SSA/Ps伴粘膜下癌，19例经典腺瘤，26例腺瘤伴高级别异型增生和25例腺瘤伴粘膜下癌行直接BRAF/KRAS测序。锯齿状系列组织中核β-catenin标记显著低于对应腺瘤组织，但从SSA/Ps到SSA/Ps伴高级别异型增生或伴粘膜下癌中β-catenin标记增量明显。SSA/Ps系列中MLH1和SFRP4甲基化的发生率显著高于相应腺瘤系列。与相应腺瘤系列相比，SSA/Ps伴高级别异型增生和粘膜下癌时更常见AXIN2和MCC甲基化。从SSA/Ps经SSA/Ps伴高级别异型增生过渡到SSA/Ps伴粘膜下癌可见AXIN2和MCC甲基化阶梯式增加。SSA/Ps系列中，核β-catenin表达和AXIN2或MCC甲基化之间具有显著相关性。与腺瘤系列相比，SSA/Ps系列中BRAF突变更为常见，而KRAS突变不常见。SSA/P系列中，BRAF突变与AXIN2甲基化呈负相关。总之，通过SFRP4，MCC,和AXIN2甲基化调节的WNT/β-catenin信号激活可能对锯齿状和传统通路结直肠肿瘤发挥不同的作用。
AbstractSessileserratedadenoma/polyp(SSA/P)isconsideredasanearlyprecursorintheserratedneoplasiapathwayleadingtocolorectalcancerdevelopment.Theconventionaladenoma-carcinomasequenceisassociatedwithactivationoftheWNTsignalingpathway,althoughitsroleinserratedlesionsisstillcontroversial.ToclarifydifferencesinWNTsignalingactivationinassociationwithMLH1methylationorBRAF/KRASmutationsbetweenserratedandconventionalroutes,weperformedβ-cateninimmunostaining,methylation-specificPCRforMLH1andWNTsignalingassociatedgenessuchasAXIN2,APC,andMCCandsecretedfrizzled-relatedproteins(SFRPs),anddirectsequencingofBRAF/KRASin27SSA/Ps,14SSA/Pswithhigh-gradedysplasiaand9SSA/Pswithsubmucosalcarcinoma,aswellas19conventionaladenomas,26adenomaswithhigh-gradedysplasiaand25adenomaswithsubmucosalcarcinoma.Nuclearβ-cateninlabelingsweresignificantlylowerintheserratedseriesthanintheiradenomacounterparts,andasignificantincrementinthoselabelingswasfoundfromSSA/Pstothosewithhigh-gradedysplasiaorsubmucosalcarcinoma.ThefrequencyofMLH1andSFRP4methylationwassignificantlyhigherinSSA/Pseries,as怎样判断得了白殿风北京治疗白癜风要多少钱啊