食管癌前病变及原位癌组织中Ki67、p53、iNOS的异常表达

目的研究食管癌高发区癌前病变及癌活检组织标本中Ki67、p53蛋白的异常表达，探讨其与食管癌变的关系及作为早期癌变生物学标志物的可能性。方法对来自食管癌高发区河北磁县的正常食管黏膜组织和轻度、中度、重度不典型增生上皮以及原位癌活检组织共366例，应用免疫组化技术对食管癌变过程中Ki67、p53蛋白的异常表达进行研究。结果在正常黏膜、轻度、中度、重度不典型增生及原位癌组织中，Ki67异常表达检出率分别为0(0/25)、40.5%(30/74)、61.3%(65/106)、76.5%(39/51)和90.0%(72/80)，其中异常表达程度在中度以上者分别占0(0/25)、2.7%(2/74)、11.2%(12/106)、41.2%(21/51)和58.8%(47/80)；p53蛋白异常表达的阳性率分别为4%(1/25)、39.1%(27/69)、57.5%(61/106)、52.9%(27/51)和67.9%(53/78)，其中异常表达程度在中度以上者分别占0(0/25)、10.1%(7/69)、24.5%(26/106)、39.2%(20/51)和48.7%(38/78)。p53蛋白及Ki67在正常黏膜中的表达，与不典型增生总体及原位癌组织的差异均有显著性(P＜0.001)。等级相关分析结果显示，p53、Ki67表达异常与组织学分级均显著相关（相关系数r分别为0.3597和0.5837，P值均＜0.001)，而且p53蛋白与Ki67表达之间也具有显著相关性（r=0.5432，P＜0.001）。结论Ki67、p53蛋白异常表达与食管癌癌变过程显著相关，p53基因表达异常及细胞增殖异常与食管上皮的早期癌变有关。p53及Ki67表达改变的时相分布，有可能成为在食管癌前人群中确立高危个体和选择重点化学预防个体的分子生物学标记。p53改变可促使上皮细胞增殖。

Abnormal expression of p53,Ki67 and iNOS in human esophage al carcimoma in situ and pre-malignant lesions

OBJECTIVE: To investigate alterations in expression of Ki67, p53 and iNOS proteins in esophageal carcinogenesis. METHODS: The expression of Ki67, p53 and iNOS proteins was detected by immunohistochemical staining of 366 endoscopic biopsy specimens of the esophagus collected from high incidence area of esophageal cancer in China. If the intensity of staining was scored as > or = ++, it was regarded as overexpression. RESULTS: The overespression rate of Ki67 was 0 for normal epithelium(NE), 2.7% for mild dysplasia (MD), 11.2% for moderate dysplasia (MoD), 41.2% for severe dysplasia (SD), and 58.8% for carcinoma in-situ(CIS), respectively. That of p53 and iNOS proteins was 0 and 0 for NE, 10.1% and 4.0% for MD, 24.5% and 7.5% for MoD, 39.2% and 2.5% for SD, 48.7% and 1.4% for CIS, respectively. There was significant difference in the expression of Ki67 and p53 between normal epithelium and dysplasia of various degrees and CIS. Overexpression of Ki67 and p53 correlated well with the pathological grading of the lesions. Positive correlation was also found between p53 and Ki67 overexpressions. CONCLUSION: Overexpression of Ki67 and p53, but not iNOS, is associated with carcinogenesis of the esophagus. They are early events in esophageal carcinogenesis and useful biomarkers for early detection.