Department of Gastroenterology and Metabolism, Hiroshima University Hospital, Health Service Center, Hiroshima University, 1-2-3 Kasumi, Minami-ku, Hiroshima 734-8551, Japan.
Oncol Rep. 2011 Feb;25(2):453-9. doi: 10.3892/or.2010.1110. Epub 2010 Dec 14.
Whether multiple esophageal squamous cell carcinomas (SCCs) in a patient develop through an identical genetic pathway is still unclear. We examined multiple esophageal SCCs for alterations of p53, p16, IRF and mitochondrial DNA (mtDNA) and microsatellite instability (MSI). Thirty patients with multiple superficial esophageal SCCs, 23 with double lesions and 7 with triple lesions, were enrolled. Loss of heterozygosity (LOH) of p53 (TP53), p16 (D9S171), IRF (IRF) and other microsatellite loci including D1S191, D17S858, D18S58 and D18S61 of the tumors was examined by microsatellite assay. Mutations of p16 and mtDNA were examined with PCR single-strand conformation polymorphism (SSCP) analysis. LOH of p53, p16 and IRF were detected in 16 of 50 (32%), 5 of 38 (13%) and 5 of 48 (10%) tumors, respectively. Mutations of p16 were detected in 4 of 67 (6%) tumors. Six of 67 (9%) tumors had mtDNA alterations and none of the tumors showed high-frequency MSI. All 30 patients showed one or more gene alterations in one or more genetic loci. Discordant genetic patterns among individual lesions within a patient were observed in 28 of the 30 (93%) patients. The most discordant locus was TP53, present in 11 of 29 (38%) informative cases, followed by D18S61, present in 11 of 30 (37%) informative cases. These results suggest that the genetic pathways of multiple esophageal SCCs may differ even within the same patient.
在一个患者中，多个食管鳞状细胞癌（SCC）是否通过相同的遗传途径发展尚不清楚。我们检查了多个食管 SCC 的 p53、p16、IRF 和线粒体 DNA（mtDNA）以及微卫星不稳定性（MSI）的改变。纳入了 30 名患有多发性浅表性食管 SCC 的患者，23 名患有双病灶，7 名患有三病灶。通过微卫星分析检查肿瘤中 p53（TP53）、p16（D9S171）、IRF（IRF）和其他微卫星位点（包括 D1S191、D17S858、D18S58 和 D18S61）的杂合性丢失（LOH）。使用 PCR 单链构象多态性（SSCP）分析检查 p16 和 mtDNA 的突变。在 50 个肿瘤中检测到 16 个（32%）、38 个中的 5 个（13%）和 48 个中的 5 个（10%）肿瘤中的 LOH p53、p16 和 IRF。在 67 个肿瘤中检测到 4 个（6%）肿瘤中的 p16 突变。67 个肿瘤中有 6 个（9%）有 mtDNA 改变，没有一个肿瘤显示高频 MSI。所有 30 名患者在一个或多个遗传位点中均有一个或多个基因改变。在 30 名患者中的 28 名（93%）患者中观察到患者内个体病变之间的不一致遗传模式。最不一致的位点是 TP53，在 29 个有信息的病例中有 11 个（38%），其次是 D18S61，在 30 个有信息的病例中有 11 个（37%）。这些结果表明，即使在同一患者中，多个食管 SCC 的遗传途径也可能不同。
