细胞凋亡及p53蛋白表达与Barrett食管及食管腺癌发病的关系

The Correlation between Apoptosis and p53 Protein in the Pathogenesis of Barrett Esophagus and Esophageal Adenocarcinoma

目的研究细胞凋亡及相关的p53蛋白表达与巴雷特食管、食管腺癌发生和进展的关系。方法将2009年1~12月就诊于南京军区福州总医院消化内科的50例巴雷特食管患者及25例食管腺癌患者纳入研究,通过活检或手术取得食管病灶处黏膜组织,另取上述患者（各10例）的正常食管鳞状上皮作为对照组。采用细胞凋亡原位检测技术（TUNEL染色法）检测细胞凋亡情况,用快捷免疫组织化学MaxVisionTM法检测p53蛋白表达,并进行组间比较和相关分析。结果巴雷特食管的凋亡指数与正常食管鳞状上皮比较差异无统计学意义（P=0.215）,而食管腺癌的凋亡指数显著低于巴雷特食管和正常食管上皮（P〈0.01）;p53蛋白在正常食管上皮不表达,在巴雷特食管上皮细胞核中呈弱表达,而在食管腺癌细胞核中呈强阳性表达,与正常食管及巴雷特食管比较,差异均有统计学意义（P〈0.01）;p53蛋白在正常食管黏膜、巴雷特食管及食管腺癌中表达呈递增趋势（r s=0.621,P〈0.01）。在巴雷特食管与食管腺癌中,p53蛋白表达与细胞凋亡呈负相关（r s=-0.660,P〈0.01）。结论巴雷特食管发生并向食管腺癌发展过程中,凋亡抑制机制可能起重要作用,而突变型p53可能通过抑制细胞凋亡参与巴雷特食管及食管腺癌的发生、发展。

Objective To investigate the role of apoptosis and p53 protein in the pathogenesis of Barrett esophagus（ BE） and esophageal adenocarcinoma（ EA）. Methods The apoptotic index（ AI） and the expression of p53 protein of 50 BE patients and 25 EA patients admitted to Fuzhou General Hospital of Nanjing Command from Jan. 2009 to Dec. 2009 were included in the study,esophageal mucosa lesion tissue were obtained through biopsy or operation,and normal esophageal squamous epithelium of the above patients（ 10 cases of each） were obtained as control. TUNEL method was used to test apoptosis and MaxVisionTM immunohistochemical staining assay was used to test p53 expression respectively. Comparison and analysis between the groups were done. Results The average AI of BE was higher than that of normal esophageal squamous epithelium,but there was not a statistical significance（ P = 0. 215）. The AI of EA was lower than that of normal esophageal squamous epithelium and BE（ P 0. 01）. The expression of p53 protein was not seen in normal esophageal squamous epithelium,low expression in BE,high expression in EA（ P 0. 01）. Moreover,we also observed an increasing tendency in the three groups（ r s = 0. 621,P 0. 01）. Simultaneously,a negative correlation（ r s =0. 660,P 0. 01） between p53 expression and AI was found in BE and EA. Conclusion Inhibition of apoptosis may play an important role in the occurrence of BE and its progress to EA. Mutant p53 may contribute to carcinogenesis of BE cells by inhibiting apoptosis.