MAPK、MMP-2和MMP-9在唾液腺腺样囊性癌中的表达及临床意义

Expression and clinical significance of MAPK,MMP-2 and MMP-9 in salivary adenoid cystic carcinoma

目的:研究人唾液腺腺样囊性癌组织中MAPK(p-ERK1/2、p-P38及p-JNK)、MMP-2和MMP-9的表达情况,探讨其与临床病理特征的关系。方法:应用免疫组织化学SP法检测27例腺样囊性癌组织标本(癌组)和15例正常唾液腺组织标本(对照组)中p-ERK1/2、p-P38、p-JNK、MMP-2和MMP-9的表达情况。采用SPSS17.0软件包对数据进行统计学分析。结果:p-ERK1/2、p-P38、p-JNK、MMP-2和MMP-9在腺样囊性癌组中的阳性表达率(分别为81.48%、88.89%、70.37%、81.49%和77.78%)均显著高于在正常唾液腺对照组中的阳性表达率(分别为20%、26.67%、26.67%、26.67%和26.67%),差异有统计学意义(分别为P<0.01、P<0.01、P<0.05、P<0.01和P<0.01)。腺样囊性癌组织中p-ERK1/2、p-P38、MMP-2和MMP-9在Ⅲ～Ⅳ期组的阳性表达率(分别为88.89%、100%、94.44%和94.44%)显著高于Ⅰ～Ⅱ期组(分别为44.44%、66.67%、55.56%和44.44%),差异有统计学意义(分别为P<0.01、P<0.01、P<0.01和P<0.05),但p-JNK的表达与临床分期无统计学关系(P>0.05);p-ERK1/2、p-P38、p-JNK、MMP-2和MMP-9的表达与患者的性别、年龄、原发肿瘤部位、病理分型以及有无神经侵袭、复发和转移亦均无相关性(均为P>0.05);p-ERK1/2、p-P38、p-JNK与MMP-2和MMP-9的表达分别呈显著正相关(分别为r=0.786,P<0.001;r=0.796,P<0.001;r=0.824,P<0.001和r=0.768,P<0.001;r=0.581,P<0.01;r=0.604,P<0.01)。结论:p-ERK1/2、p-P38、p-JNK、MMP-2和MMP-9的高表达与腺样囊性癌的临床分期及进展密切相关。MAPK/MMPs通路可能参与腺样囊性癌的发生、发展、侵袭及转移过程。

PURPOSE： To investigate the expression of MAPK（p-ERK1/2、p-P38 and p-JNK）,matrix metalloproteinase-2（MMP-2） and matrix metalloproteinase-9（MMP-9） in human salivary adenoid cystic carcinoma（SACC） tissues,and to explore their relation with clinicopathological features.METHODS： SP immunochemistry staining method was employed to detect protein expression of MAPK,MMP-2 and MMP-9 in the paraffin-embedded specimens from 27 cases with human SACC and 15 cases with normal human salivary epithelial tissues.All data were analyzed by SPSS17.0 software package.RESULTS： Positive expression rates of p-ERK1/2,p-P38,p-JNK,MMP-2 and MMP-9 were 81.48%,88.89%,70.37%,81.49% and 77.78% in SACC tissues and 20%,26.67%,26.67%,26.67% and 26.67% in normal salivary tissues,respectively.The expression of p-ERK1/2,p-P38,p-JNK,MMP-2 and MMP-9 in SACC tissues increased compared with normal salivary tissues respectively（P0.01,P0.01,P0.05,P0.01 and P0.01）.Positive expression rates of p-ERK1/2,p-P38,MMP-2 and MMP-9 at the third and forth clinical stage（88.89%,100%,94.44% and 94.44%） were higher than that at the first and second clinical stage（44.44%,66.67%,55.56% and 44.44%） in SACC.The differences were statistically significant（P0.01,P0.01,P0.01 and P0.05,respectively）;Positive expression rate of p-JNK was not significantly correlated with clinical stages（P0.05）;Positive expression rates of p-ERK1/2,p-P38,p-JNK,MMP-2 and MMP-9 were not significantly correlated with patient＇s gender,age,primary site,pathological type,neural invasion,local recurrence as well as distant metastasis（P0.05）.p-ERK1/2,p-P38 and p-JNK had a positive relationship with MMP-2 and MMP-9 in protein expression in SACC,respectively（r=0.786,P0.001;r=0.796,P0.001;r =0.824,P0.001 and r=0.768,P0.001;r=0.581,P0.01;r=0.604;P0.01,respectively）.CONCLUSION： Increased expression of p-ERK1/2,p-P38,p-JNK,MMP-2 and MMP-9 may be associated with clinical progression of SACC,and they may participate in the process of SACC initiation,progression,invasion and metastasis by activating the MAPK/MMPs pathway.