CAJ | 학술논문

目的检测β-连环蛋白(β -catenin)在胰腺正常导管(NP)、胰腺上皮内瘤变(PanINs)、胰腺导管内乳头状黏液性肿瘤( IPMNs)及胰腺导管腺癌(PDAC)中的表达水平,分析其在胰腺癌发生过程中的作用.方法收集正常胰腺组织12例、IPMN 52例(IPMA 20例,IPMB 13例,IPMC 19例)、PanINs118灶(PanIN-1 73灶,PanIN-2 29灶,PanIN-3 16灶)、PDAC 50例,采用免疫组化SP法检测β-catenin在上述组织中的表达,并分析其在胰腺癌的表达与临床病理特征及患者术后生存期的关系.结果 NP中β-catenin主要表达于细胞膜,表达量为(4.38±2.11)分；PanINs、PDAC和IPMN的β-catenin膜表达明显降低或缺失,PanIN-1、PanIN-2、PanIN-3、PDAC、IPMA、IPMB、IPMC的膜表达量分别为(5.22±2.21)、(2.24 ±2.31)、(1.44±1.37)、(2.71 ±2.08)、(4.85±2.28)、(4.15±2.51)、(2.68±2.75)分.PanIN-1的胞质表达率为12.3％ (9/73),胞核表达率为0；PanIN-2为34.5％ (10/29)和3.4％ (1/29)；PanIN-3为43.8％ (7/16)和12.5％ (2/16)；PDAC为44.0％ (22/50)和10.0％( 5/50).在由PanINs至PDAC的进展过程中β-catenin膜表达逐渐降低,而胞质、胞核异位表达率逐渐升高.β-catenin膜表达与肿瘤大小、神经浸润、淋巴转移有关(P＜0.05)；胞质异位表达率与肿瘤大小有关(P＜0.05)；胞核异位表达率与肿瘤的分化程度有关(P＜0.01)；胞膜、胞质表达均与患者的术后生存期显著相关(P＜0.05).结论 Wnt/β-catenin通路异常活化导致的β-catenin膜表达减弱及异位表达率增加是PDAC发生、发展的重要机制,并促进PDAC的恶性生长与转移,β-catenin的表达与PDAC患者的预后相关.
목적 검측β-련배단백(β -catenin)재이선정상도관(NP)、이선상피내류변(PanINs)、이선도관내유두상점액성종류( IPMNs)급이선도관선암(PDAC)중적표체수평,분석기재이선암발생과정중적작용.방법 수집정상이선조직12례、IPMN 52례(IPMA 20례,IPMB 13례,IPMC 19례)、PanINs118조(PanIN-1 73조,PanIN-2 29조,PanIN-3 16조)、PDAC 50례,채용면역조화SP법검측β-catenin재상술조직중적표체,병분석기재이선암적표체여림상병리특정급환자술후생존기적관계.결과 NP중β-catenin주요표체우세포막,표체량위(4.38±2.11)분；PanINs、PDAC화IPMN적β-catenin막표체명현강저혹결실,PanIN-1、PanIN-2、PanIN-3、PDAC、IPMA、IPMB、IPMC적막표체량분별위(5.22±2.21)、(2.24 ±2.31)、(1.44±1.37)、(2.71 ±2.08)、(4.85±2.28)、(4.15±2.51)、(2.68±2.75)분.PanIN-1적포질표체솔위12.3％ (9/73),포핵표체솔위0；PanIN-2위34.5％ (10/29)화3.4％ (1/29)；PanIN-3위43.8％ (7/16)화12.5％ (2/16)；PDAC위44.0％ (22/50)화10.0％( 5/50).재유PanINs지PDAC적진전과정중β-catenin막표체축점강저,이포질、포핵이위표체솔축점승고.β-catenin막표체여종류대소、신경침윤、림파전이유관(P＜0.05)；포질이위표체솔여종류대소유관(P＜0.05)；포핵이위표체솔여종류적분화정도유관(P＜0.01)；포막、포질표체균여환자적술후생존기현저상관(P＜0.05).결론 Wnt/β-catenin통로이상활화도치적β-catenin막표체감약급이위표체솔증가시PDAC발생、발전적중요궤제,병촉진PDAC적악성생장여전이,β-catenin적표체여PDAC환자적예후상관.
Objective To detect the expressions of β-catenin protein in different pancreatic tissues ( NP,PanINs,IPMNs and PDAC) and evaluate its significance during the carcinogenesis of PDAC.Methods The expression of β-catenin protein in 12 samples of normal pancreatic tissues,52 samples of IPMN (IPMA 20 foci,IPMB 13 foci,IPMC 19 foci),PanINs 118 foci (PanIN-1 73 foci,PanIN-2 29 foci,PanIN-3 16 foci),50 cases of PDAC was determined by using immunohistochemistry. The correlation between β-catenin expression and clinicopathologic characteristics of PDAC was analyzed. Results β-catenin was mainly expressed in cell membrane of NP,the quantity was 4.38 ± 2.11 ; in PanINs,PDAC and IPMN,β-catenin membrane expression was significantly decreased or absent,the β-catenin membrane expressions of PanIN-1,PanIN-2,PanIN-3,PDAC,IPMA,IPMB,IPMC were 5.22 ±2.21,2.24 ±2.31,1.44 ±1.37,2.71 ±2.08,4.85 ±2.28,4.15 ±2.51,2.68 ±2.75.The cytoplasm expression of PanIN-1 was 12.3％ (9/73),while the nuclear expression was 0 ; and the corresponding values were 34.5％ (10/29) and 3.4％ ( 1/29 ) in PanIN-2; 43.8％ (7/16) and 12.5％ (2/16) in PanIN-3; 44.0％ (22/50) and 10.0％ (5/50) in PDAC.The IHCS of β-catenin membrane expression decreased with the severe tissue atypia along the progressive multistage.The β-catenin membrane expression was significantly associated with tumor size,neural infiltration and lymphatic metastasis ( P ＜ 0.05 ).Ectopic cytoplasm expression was significantly associated with tumor size (P ＜0.05 ). Ectopic nuclear expression was significantly associated with tumor differentiation (P＜0.01).The membrane or ectopic cytoplasm expression of β-catenin was significantly associated with postoperative survival.Conclusions Abnormal Wnt/β-catenin signal activation induces decreased β-catenin membrane expression and increased ectopic expression,which is an important mechanism of pathogenesis and development of PDAC,and promotes the growth and metastasis of PDAC.The expression of β-catenin was associated with postoperative survival.