Yoshida T, Sugai T, Habano W, Nakamura S, Uesugi N, Funato O, Saito K
Division of Pathology, School of Medicine, Iwate Medical University, Morioka, Japan.
J Gastroenterol. 2000;35(10):768-74. doi: 10.1007/s005350070036.
Although the genetic basis for gallbladder carcinogenesis has not been clarified, considerable evidence has shown that genetic alterations play an important role in the development and progression of human cancers. In this study, we analyzed 30 gallbladder carcinomas to investigate the role of genetic alterations in their tumorigenesis, and to study correlations with their clinicopathological features. Tissue samples were obtained from 30 patients with gallbladder carcinoma (11 men and 19 women; mean age, 62 years; age range, 38-80 years). Genomic DNAs were extracted from fresh tumor tissue. We examined loss of heterozygosity (LOH) in the p53, APC, DCC, RB, and NM23-H1 gene regions by polymerase chain reaction (PCR)-LOH assay using an automated fluorescent DNA sequencer employing four microsatellite markers (p53, APC, DCC, NM23-H1). Five additional microsatellite markers were used for the determination of microsatellite instability (MSI). LOH was found at p53 in 9 of 15 informative cases (60%), at DCC in 10 of 22 (45%), at APC in 5 of 15 (33%), at RB in 1 of 8 (13%), and at NM23-H1 in 1 of 15 (7%). MSI was observed in 5 of 30 cases (17%) in at least one chromosomal loci of these nine microsatellite markers. None of the patients with MSI-positive tumors showed lymph node metastasis, and there was an inverse correlation between MSI and the presence of LOH in gallbladder carcinoma. These results suggest that there are two independent genetic pathways in gallbladder carcinogenesis; that is, an MSI pathway and an LOH pathway.
尽管胆囊癌发生的遗传基础尚未阐明，但大量证据表明基因改变在人类癌症的发生和发展中起重要作用。在本研究中，我们分析了30例胆囊癌，以研究基因改变在其肿瘤发生中的作用，并研究其与临床病理特征的相关性。组织样本取自30例胆囊癌患者（11例男性和19例女性；平均年龄62岁；年龄范围38 - 80岁）。从新鲜肿瘤组织中提取基因组DNA。我们使用自动荧光DNA测序仪，通过聚合酶链反应（PCR）-杂合性缺失（LOH）分析，利用四个微卫星标记（p53、APC、DCC、NM23-H1）检测p53、APC、DCC、RB和NM23-H1基因区域的杂合性缺失。另外使用五个微卫星标记来测定微卫星不稳定性（MSI）。在15例信息充分的病例中，9例（60%）p53基因存在LOH，22例中的10例（45%）DCC基因存在LOH，15例中的5例（33%）APC基因存在LOH，8例中的1例（13%）RB基因存在LOH，15例中的1例（7%）NM23-H1基因存在LOH。在这30例病例中，5例（17%）在这九个微卫星标记的至少一个染色体位点观察到MSI。MSI阳性肿瘤患者均未出现淋巴结转移，并且胆囊癌中MSI与LOH的存在呈负相关。这些结果表明胆囊癌发生存在两条独立的遗传途径；即，MSI途径和LOH途径。
