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

在30个食管鳞状细胞癌（ESC）细胞系中，28个（93.3%）显示p16基因的畸变：在15个原发性食管肿瘤中，7个（41%）检测到p16基因的畸变，而所有来自这些肿瘤的细胞系均显示畸变。我们在9个细胞系中检测到纯合缺失，这些细胞系是从没有它们的肿瘤中建立的，并且所有这些缺失甚至在早期传代的培养物中也观察到。这些结果表明，肿瘤中表现出纯合缺失的细胞通过建立细胞系而扩增的可能性。关于p53突变，在29个细胞系中，22个（75.9%）显示p53突变。与这些新鲜肿瘤材料中的结果相比，细胞系中的突变发生率明显较高，且突变谱也不同。在从无突变肿瘤建立的7个细胞系中，在5个细胞系中检测到新获得的突变，这表明突变可能发生在建立细胞系的过程中。 ...更多信息 APC基因缺失、p53基因突变、CyclinD 1基因扩增和MDM 2基因扩增患者的预后明显低于无基因异常者。p53突变和MDM 2扩增的联合分析获得了最佳的预测性。联合Rb基因和CyclinD 1基因检测发现Rb基因缺失对食管癌患者的预后有重要意义，并探讨了基因异常与食管癌患者组织学效应的关系。无p53突变的患者中62.5%（15/24）出现组织学效应（>0级），而19例p53突变患者中6例（31.6%）出现组织学效应。手术切除标本及治疗前活检标本中p53免疫组化阳性病例也有顺铂耐药的趋势。p53基因突变及其调控基因可作为食管鳞癌化疗敏感性的标志，根据p53基因突变及其调控基因的检测结果选择化疗方案。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