食管黏膜凋亡增殖和p53表达的增龄变化与食管鳞癌的关系

目的探讨食管黏膜增殖凋亡和p53表达的增龄变化以及这些变化与食管鳞癌的关系。方法按年龄分层选择连续胃镜检查对象818例,男414例,女404例。分为青中年组（258例）、老年前期组（296例）和老年组（264例）,进行食管活组织检查,应用TUNEL法检测凋亡指数（AI）,免疫组化法检测增殖指数（PI）和p53表达。结果食管正常上皮→单纯增生→轻中重度异型增生→鳞癌的发展过程中,AI等级逐渐下降,PI等级和p53表达逐渐增高。在食管正常上皮中,AI等级青中年组〉老年前期组〉老年组;PI等级比较,老年前期组分别高于青中年组和老年组（P〈0.01）;p53表达在老年前期组和老年组均高于青中年组（P〈0.01）。非条件logistic回归分析,食管鳞癌独立危险因素为增龄、PI等级和p53表达。当食管黏膜PI等级明显增高伴p53阳性时,鳞癌检出率明显增高,轻中重度异型增生有增高趋势,老年人尤为突出。结论食管黏膜正常上皮随增龄出现增殖凋亡和p53表达变化,与食管黏膜癌变过程变化相似,老年人食管黏膜PI明显增高伴p53阳性可作为食管鳞癌和癌前病变进一步随访和筛查的线索。

Relationship of apoptosis, proliferation of epithelial cells and the expression of p53 in esophageal mucous membrane with esophageal squamous cell carcinoma

Objective To investigate the realationship of apoptosis,proliferation of epithelial cells and the expression of p53 in esophageal mucous membrane with esophageal squamous cell carcinoma(ESCC).Methods 818 patients(414 male and 404 female)who received gastroscopy were selected and divided into youth and midlle-aged group(n=258),presenile group(n=296)and senile group(n=264).All cases received biopsy in esophagus.The specimens were examined by histopathology.Apoptosis index was detected by TUNEL,proliferating cell nuclear antigen(PCNA)and p53 detected by immunohistochemistry.Results In development of the normal epithelium of esophagus→simple hyperplasia→mild-moderate dysplasia→ESCC,the grade of apoptosis gradually declined and the grade of PCNA and p53 gradually rose.In normal epithelium of esophagus,the grade of apoptosis index was highest in youth and midlle-aged group,followed by presenile group,senile group.The grade of PCNA index in presenile group was higher than that in youth and midlle-aged group and senile group respectively(P<0.01);p53 expression grade in presinle group and senile group was higher than that in youth and middle-aged group(P<0.01).The independent risk factors of ESCC were aging,grade of PCNA index and the expression of p53.When increased PCNA grade was combined with positive p53 in esophageal mucous membrane,the rate of ESCC was obviously increased,and mild-moderate dysplasia trended to increase,especially in senile group.Conclusions There are changes of apoptosis,proliferation and expression of p53 in normal epithelium of esophageal mucous membrane accompanied by aging,similar with cancerative process.In senile,the high PCNA index with positive p53 may be a clue for further follow up and screening of ESCC and precancerous lesions.