SEL 1L和Smad 4蛋白表达与食管癌生物学行为的相关性研究

Expression and Clinical Significance of SEL 1L and Smad 4 Protein in Esophageal Cancer

目的探讨食管癌组织中的SEL 1L蛋白、Smad 4蛋白的表达与食管癌生物学行为的相关性。方法应用免疫组织化学S-P法检测90例手术切除的食管鳞状细胞癌,35例距癌灶边缘5cm以上切缘的正常黏膜,60例癌旁黏膜及20例内窥镜活检的食管鳞状上皮不典型增生组织中SEL 1L蛋白和Smad4蛋白的表达。结果(1)SEL 1L蛋白在食管鳞状细胞癌的表达阳性率为87.8%,在食管鳞状上皮不典型增生中的表达阳性率为90.0%,分别较食管正常黏膜(14.3%)和癌旁黏膜(13.3%)高(P<0.01)。SEL 1L蛋白表达与患者性别、年龄和肿瘤的位置、大小、分化程度、浸润深度、淋巴结转移及临床分期均无明显相关性(P>0.05)。(2)Smad 4蛋白在食管鳞状细胞癌的表达阳性率为48.9%,较食管正常黏膜(88.6%)、癌旁黏膜(83.3%)和食管鳞状上皮不典型增生(70.0%)低(P<0.01);临床分期ⅡB+Ⅲ期和有淋巴结转移的食管鳞状细胞癌组织Smad 4蛋白的阳性率明显低于临床分期Ⅰ+ⅡA期和无淋巴结转移的食管鳞状细胞癌组织(P<0.05);Smad 4蛋白的表达与肿瘤组织分化程度呈正相关(r=0.347,P<0.01),而与患者性别、年龄和肿瘤的位置、大小、浸润深度无明显相关性(P>0.05)。(3)食管鳞状细胞癌组织中SEL 1L蛋白和Smad 4蛋白的表达呈明显负相关(r=-0.314,P<0.01)。结论(1)SEL 1L蛋白过表达可能是食管鳞状细胞癌发生的早期表现,SEL 1L蛋白的检测可作为识别食管癌高风险患者的生物学标记物。(2)Smad 4蛋白的低表达在食管癌的发展及侵袭转移中具有重要作用。(3)SEL 1L蛋白和Smad 4蛋白在食管癌的发生发展过程中具有协同作用;联合检测食管癌中SEL 1L蛋白和Smad 4蛋白的表达,比单一检测一种蛋白对评估食管癌的发生、发展及预后更具有意义,也为临床治疗食管癌提供了一条新的思路。

Objective To investigate the relationship between the expression of SEL 1L protein ,Smad 4 protein and the biological behavior in esophageal cancer. Methods Immunohistochemical staining（S-P method） for SEL 1L protein and Smad 4 protein were performed in 90 esophageal carcinoma,35 normal esophageal tissues 5 cm distant from tumors,60 esophageal mucosa adjacent to tumors and 20 esophageal dysplasia. Results （ 1 ） The positive rate of SEL 1L protein was higher in esophageal carcinoma（ 87. 8% ）, esophageal dysplasia（ 90. 0% ） , compared with normal esophageal mucosa（ 14. 3% ） and esophageal mucosa adjacent to tumors（ 13.3% ） respectively. The difference was significant（ P 〈0.01 ）. The expression of SEL 1L protein in esophageal squamous cell cancer was not related to any clinicopathological parameters（ P 〉 0. 05 ）. （2）The positive rate of Smad 4 protein was lower in esophageal careinoma（48. 9% ）, compared with normal esophageal mucosa（ 88.6% ）, esophageal mucosa adjacent to tumors （83.3%） and esophageal dysplasia（70. 0% ）. The difference was significant（ P 〈0. 01 ）. The positive rates of Smad 4 protein were significantly lower in the tissue of clinical stage ⅡB ＋ Ⅲ stages and with lymph node metastasis than that of clinical stage Ⅰ ＋ Ⅱ A stages and with- out lymph node metastasis（ P 〈0. 05 ）. The expression of Smad 4 protein was positively correlated with degree of differentiation of carcinoma（ r = 0. 347, P 〈 0. 01 ）, moderately and poorly differentiated carcinomas had lower Smad 4 protein expression than well differentiated carcinomas, but not with gender,age, tumor location, tumor size and depth of tumor invasion （ P 〉 0.05 ）. （3） A negative correlation was found between the expression of SEL 1L protein and Smad 4 protein（ r = -0.314, P 〈0.01）. Conclusion （1） Overexpression of SEL 1L protein might be an early event during the formation of esophageal squamous cell cancer. SEL 1L protein might be an important biomarker in the identification of those patients at higher risk of developing esophageal carcinoma. （2） Lower expression of Smad 4 protein might play an important role in progression,invasion and metastasis of esophageal cancer. （ 3 ） SEL 1L protein and Smad 4 protein play important roles in carcinogenesis of esophageal cancer teghther. It was much more significant and a new treatment approach to investigate the expression of SEL 1L and Smad 4 combinedly in esophageal cancer than to investigate the expression of only one of them.