Analysis of Cell Cycle Related Gene and Cell Culture in Esophageal Cancer. (Carcinogenesis, Tumor Progression and Prognostic Factor)

在30个食管鳞癌(ESC)细胞系中，28个(93.3%)发生了p16基因的异常；在15个原发性食管瘤中，有7个(41%)出现了p16基因的异常，而所有来源于这些肿瘤的细胞系都出现了异常。我们在9个没有纯合缺失的肿瘤细胞系中检测到了纯合子缺失，即使在传代早期的培养中也观察到了所有这些缺失。这些结果表明，在肿瘤中出现纯合子缺失的细胞可能是通过建立细胞系而扩增的。关于p53突变，在29个细胞系中，有22个(75.9%)出现了p53突变。与新鲜肿瘤材料的结果相比，细胞株的突变率明显较高，突变谱也不同。在从无突变的肿瘤中建立的7个细胞系中，有5个新获得的突变被检测到，这表明突变可能发生在建立…的过程中APC基因缺失、P53基因突变、细胞周期蛋白D1扩增和MDM2扩增患者的预后明显低于无基因异常患者。联合分析P53突变和MDM2扩增可获得最好的预测性。通过对Rb基因和细胞周期蛋白D_1基因的联合分析，发现Rb基因缺失对患者的预后有重要影响。最后，我们对乳腺癌患者的基因异常与组织学疗效的关系进行了检验。62.5%(15/24)的无P53突变患者组织学效果为0级，而19例P53突变患者中有6例(31.6%)有组织学效果。免疫组织化学P53阳性病例在切除标本和治疗前活检标本中也倾向于对顺铂耐药。P53突变及其调控基因可能是食管鳞癌化疗敏感性的指标，可根据P53突变及其调控基因的检测结果选择化疗方案。较少

Of the 30 esophageal squamous cell carcinoma (ESC) cell lines, 28 (93.3%) showed aberration of the p16 gene : Of the 15 primary esophageal tumors, aberrations of the p16 gene were detected in 7 (41%), while all cell lines derived from these tumors showed aberrations. We detected homozygous deletions in 9 cell lines which were established from tumors without them, and all of these deletions were observed even in cultures at early passage. These results suggest a possibility that cells exhibiting homozygous deletions in tumors expanded through the establishment of cell lines.With regard to p53 mutation, of the 29 cell lines 22 (75.9%) showed p53 mutation. Compared with the results in these fresh tumor materials, the mutation incidence in cell lines was significantly high and the mutation spectrum was also different. In 7 cell lines established from mutation-free tumors, newly acquired mutations were detected in 5, which suggests that mutations might occur during the process of establishi … More ng cell lines.The prognosis for patients with loss of APC locus, p53 mutation, CyclinD1 amplification and MDM2 amplification was significantly lower than that of patients without gene abnormality. Best predictability was obtained by a combined analysis of p53 mutation and MDM2 amplification. Loss of Rb gene revealed to be significant on the prognosis for patients, when a combined analysis of Rb and CyclinD1 gene was made.Finaly, we checked the relation of gene abnormalities and histological effect of esophaegal cancer patients. Histological effect (grade>0) were noted in 62.5% (15/24) of the patients without p53 mutation, whereas, 6 out of 19 patients (31.6%) with p53 mutation had histological effect. The positive cases of immunohistochemical p53 staining in resected specimens and pre-treatment biopsy sample also tended to resist cisplatin. p53 mutation and its regulating genes may be a marker of chemosensitivity in esophageal SCC patients and chemotherapy may be selected according to the findings of p53 mutation and p53 regulating genes. Less