舌鳞癌中“瘤芽”的病理学特征及其与上皮-间质转化之间的关系

Study on tumor budding and its relationship with epithelial-mesenchymal transition in tongue squamous cell carcinoma

目的:探讨"瘤芽"(tumor budding)在舌鳞癌中的病理学特征及其与上皮-间质转化(EMT)的关系。方法:HE染色评估230例舌鳞癌组织标本中肿瘤侵袭前沿和"瘤芽"的分布情况;免疫组织化学染色检测E-cadherin和Vimentin在舌癌中的表达及分布;应用SPSS13.0软件包进行Sperman相关分析,探讨"瘤芽"与临床、病理参数之间的关系,Kaplan-Meier法和Logrank分析生存率。结果:在舌鳞癌组织切片中,可见"瘤芽"位于肿瘤侵袭前缘,为单个或小于5个成簇的癌细胞。在230例病例中,111例标本呈现出高"瘤芽"状态(≥5个"瘤芽"/HPF),119例标本表现出低"瘤芽"状态(<5个"瘤芽"/HPF);"瘤芽"与肿瘤大小(P<0.05)、分化程度(P<0.05)、临床分期(P<0.05)以及淋巴结转移(P<0.001)呈正相关;与患者预后呈负相关,可作为舌鳞癌患者的独立预后判断指标(P=0.0014);构成"瘤芽"的癌细胞形态可由多边形、鱼鳞状转变成长梭形、成纤维细胞样;"瘤芽"与E-cadherin的表达呈负相关(P<0.01),与Vimentin的表达呈正相关(P<0.01),提示"瘤芽"与EMT相关,是EMT在组织形态学上的一种表现。结论:"瘤芽"与EMT密切相关,代表恶性程度更高的癌细胞亚群,可作为舌鳞癌患者独立的预后判断指标。

PURPOSE： To assess the correlation of tumor budding with the clinicopathologic features,and the known molecular biomarkers（E-cadherin and Vimentin）,as well as to evaluate its prognostic significance for TSCC.METHODS：Archival clinical samples of 230 patients with TSCC were examined for tumor budding.Immunohistochemistry was performed to detect the expression of E-cadherin and Vimentin.Sperman correlation was carried out to assess the correlation of tumor budding with clinicopathologic parameters and patient＇s survival.The potential association between tumor budding and alterations of E-cadherin and Vimentin expression was also assessed with SPSS 13.0 software package.RESULTS： Of the 230 TSCC cases examined,tumor budding was observed in 165 cases（71.7%）,with a mean tumor bud count of 7.5（range from 1 to 48 buds）.High-intensity budding（≥5 tumor buds） was observed in 111 cases（48.3%）.Statistical analysis revealed that tumor budding was associated with tumor size（P0.05）,differentiation（P0.05）,clinical stage（P0.05）,lymph node metastasis（P0.01）,and correlated with decreased overall survival.In addition,significant associations were observed among tumor budding and the deregulation of E-cadherin（P0.001） and Vimentin（P0.001）.CONCLUSIONS： Tumor budding,which is associated with epithelial-mesenchymal transition,is a frequent event and appears to be an independent prognostic factor in TSCC.Supported by National Natural Science Foundation of China（81072223）.Dr.CHEN Xiao-hua and WANG Cheng contributed equally to this study.