食管癌多中心起源理论的分子学基础研究

采用免疫组化选择性ＤＮＡ序列分析方法，对来自河南省林州市２１例原发性食管鳞癌患者食管癌组织和癌旁基底细胞增生、间变和原位癌病灶的肿瘤抑制基因Ｐ５３进行比较研究。结果：２１例原发食管癌病灶中发现１４例Ｐ５３基因突变（６７％）。突变部位分别为第５外显子（４例，占２９％）、第６外显子（１例，占７％）、第７外显子（２例，占１４％）和第８外显子（６例，占４２％）。１例突变发生在第４内显子（７％）。对１４例癌旁上皮基底细胞增生、间变和原位癌病灶的Ｐ５３基因分析发现均有不同数量的基因突变。间变及原位癌组织的Ｐ５３基因突变与癌组织极为相似，但是基底细胞增生病变的Ｐ５３基因突变与癌组织不同，其突变部位均发生在第５外显子。提示：食管上皮不同部位的孤立病灶出现相似的分子学改变，支持食管癌多中心起源的理论，随着病变从基底细胞增生到间变到原位癌和早期浸润癌的发展，这些分子学变化可能在癌变的不同阶段起重要作用。

Studies of molecular basis on multiple center carcinogenesis of esophageal cancer

The special aim of the present study was to analyze the P53 gene mutation in the esophageal cancer tissue and the adjacent focal precancerous lesions at different sites from the same subject and to understand the molecular basis of multiple center carcinogenesis of the esophageal epithelium. P53 gene mutation analysis with immunohistoselective DNA sequence method was undertaken on the esopahgeal cancer tissue and the adjacent tissues with basal cell hyperplasia,dysplasia and carcinoma in situ from 21 subjects with primary esophageal squmaous cell carcinoma from Linzhou city,Henan Province.The results indicated that, of the 21 cases of primary esophageal cancer,14 cases were found with P53 gene mutation (67%).P53 mutation occurred on exon 5 (4 casese,29%),exon 6(1 case,7%),exon 7(2 cases,14%) and exon 8(6 cases,42%).One case was found of P53 mutation on intron 4(7%). The adjacent lesions of basal hyperplasis,dysplasia and carcinoma in situ from 14 cases were found with different pattern and different number of P53 gene mutation.The P53 gene mutation patterns in dysplasia and carcinoma in situ were very similar to that in the cancer tissue.The P53 mutation pattern in basal cell hyperplasia,however,was quite different from that in the cancer tissue.All the P53 mutations in basal cell hyperplasia occurred on exon 5,which was similar to those previously reported on the esophageal precancerous lesions from noncancer subjects.The present results indicated that the focal precancerous lesion adjacent to cancer tissue had similar molecular changes to that in the cancer tissue,thus supporting the multiple center carcinogenesis theory.With the lesions progressing from basal cell hyperplasia to dysplasia to carcinoma in situ and early invasive cancer,these moleculars changes may play an important role at the different stages of carcinogenesis.