摘要目的 探讨甲状腺激素受体相互作用蛋白6(TRIP6)在胰腺癌发生过程中的作用.方法 采用免疫组织化学SP法检测43例正常胰腺、18例胰腺上皮内瘤变(PanINs)及50例胰腺导管腺癌(PDAC)组织TRIP6蛋白的表达,以免疫组织化学评分(IHCS)表示其表达强弱程度,分析胰腺不同组织中TRIP6表达的差异以及PDAC组织TRIP6表达与临床病理特征的关系.结果 正常胰腺组织TRIP6阴性表达或仅有极少量表达;PanINs组织TRIP6表达随着组织异型程度增加由弱阳性表达逐渐增强;PDAC组织TRIP6强阳性表达.正常胰腺组织及PanIN-1、PanIN-2、PanIN-3、PDAC组织TRIP6表达的IHCS分别为(0.010±0.003)、(0.029±0.003)、(0.055 ±0.014)、(0.090±0.025)、(0.094±0.030)分,各组间的差异有统计学意义(P＜0.01).组间两两比较结果显示,正常胰腺组TRIP6表达量均显著低于其他4组,PanIN-1组表达量均显著低于除正常胰腺组外的其他3组,PanIN-2组表达量显著低于PanIN-3组和PDAC组,差异均有统计学意义(P值均＜0.05);PanIN-3组表达量虽然低于PDAC组,但差异无统计学意义(P=0.13).PDAC组织TRIP6表达与神经浸润(P＜0.01)、淋巴结转移(P=0.013)、远处转移(P=0.018)、胰腺癌分化程度(P =0.019)、术前CA19-9水平(P＜0.01)有关,而与患者性别、年龄及肿瘤大小、肿瘤部位、血管浸润、浸润深度、TNM分期无关.结论 TRIP6蛋白表达过强是PDAC发生过程中的早期事件,可能参与了PDAC发生、发展的全过程.

abstractsObjective To investigate the significance of Thyroid hormone receptor interactor 6 (TRIP6) in the development of pancreatic cancer.Methods The protein expression of TRIP6 was assessed immunohistochemically in 43 normal pancreatic (NP) tissues,18 pancreatic intraepithelial neoplasia (PanIN)tissues and 50 pancreatic ductal adenocarcinoma (PDAC) tissues using the immunohistochemical scores (IHCS) to evaluate the positivity of TRIP6 expression.And the expression of TRIP6 in different tissues was analyzed,and the correlations of TRIP6 expression in PDAC tissue with clinicopathological characteristics were analyzed.Results TRIP expression was negative or extremely low in normal pancreas,which changed from weak positivity to strong positivity with the increased degree of tissue atypia.TRIP6 was strongly expressed in PDAC.The IHCS of TRIP6 expression in NP,PanIN-1,PanIN-2,PanlN-3 and PDAC was(0.010 ±0.003),(0.029 ± 0.003),(0.055 ± 0.014),(0.090 ± 0.025) and (0.094 ± 0.030),and the differences were statistically significant (P ＜0.01).The results of paired comparison of either two of them above showed that the expression of TRIP6 in NP group was significantly lower than that in other four groups,the expression in PanIN-1 group was significantly lower than that in other three groups except NP group,the expression of PanIN-2 group was significantly lower than that of PanIN-3 group and PDAC group,and all the differences were statistically significant (all P ＜ 0.05).However,the expression of PanIN-3 group was lower than that of the PDAC group,but the difference was not statistically significant (P =0.13).The expression level of TRIP6 was associated with neural invasion (P＜0.01),lymph node metastasis (P=0.013),distant metastasis (P=0.018),differentiation of PDAC (P=0.019) and CA19-9 level(P＜0.01) in PDAC,but not with patients' gender,age,tumor size,location,vascular infiltration,infiltration depth and TNM stage.Conclusions Overexpression of TRIP6 is an early event in PDAC.TRIP6 may be involved in the whole process of PDAC development and progression.