Prognostic significance of microsatellite alterations at 1p36 in cholangiocarcinoma

AIM： To investigate loss of heterozygosity （LOH） and microsatellite instability （MSI） on the chromosomal region 1p36-pter in cholangiocarcinoma （CCA） patients and determine the association between microsatellite alterations and clinicopathological parameters. METHODS： Ten polymorphic microsatellite markers were determined for LOH and MSI using GS-3000 gel scan fragment autoanalyzer. RESULTS： Sixty-eight out of 90 cases （75.6%） showed LOH in one or more loci. LOH was found most frequently at DIS199 （40.0%）, DIS507 （34.6%）, DIS2845 （30.5%）, and DIS2734 （30.1%）. MSI was found in 34 of 90 cases （37.8%） at one or more loci. Fine mapping at lp36 showed two distinctive regions of common loss, which were D1S2845 and the 25.5-cM region between D1S507 and D1S2734, indicating the existence of putative tumor suppressor genes that is likely to play important roles in the development of CCA. Patients with LOH at D1S234 showed less lymphatic invasion （P = 0.017）, whereas patients with LOH at D1S2676 exhibited more lymphatic invasion than those without （P = 0.031）. LOH at D1S2845 showed a significant correlation with nerve invasion （P = 0.029）. Moreover, patients who demonstrated MSI at D1S228 showed a poor prognosis （P = 0.0026）. CONCLUSION： Allelic loss plays a major role in microsatellite alterations at chromosome lp36, which may contribute to carcinogenesis and pathogenesis of liver fluke related CCA and these alterations can be used as molecular prognostic indicators for CCA patients.

瞄准：在 cholangiocarcinoma (CCA ) 在染色体区域 1p36 磅上调查杂合现象(LOH ) 和微卫星不稳定性(MSI ) 的损失病人并且决定在微卫星改变和 clinicopathological 参数之间的协会。方法：十个多态的微卫星标记用 GS-3000 胶化扫描碎片自动分析器为 LOH 和 MSI 被决定。结果：68 在至少一部位从 90 个案例(75.6%) 显示出 LOH。LOH 最经常被发现在 D1S199 (40.0%) ， D1S507 (34.6%) ， D1S2845 (30.5%) ，和 D1S2734 (30.1%) 。MSI 在至少一部位在 90 个案例(37.8%) 中的 34 个中被发现。在 1p36 的好印射显示出普通损失的二个特殊区域，它是在 D1S507 和 D1S2734 之间的 D1S2845 和 25.5 厘米的区域，显示通常认为的肿瘤的存在压制或对可能的基因在 CCA 的发展起重要作用。有在 D1S234 的 LOH 的病人显示出不太淋巴的侵略(P = 0.017 ) ，而没有，有在 D1S2676 的 LOH 的病人比那些展出了更淋巴的侵略(P = 0.031 ) 。在 D1S2845 的 LOH 与神经侵略显示出重要关联(P = 0.029 ) 。而且，在 D1S228 表明了 MSI 的病人显示出差的预后(P = 0.0026 ) 。结论：突变而产生之遗传的损失在染色体 1p36 在微卫星改变起一个主要作用，它可以贡献肝吸虫的致癌作用和致病相关 CCA 和这些改变能为 CCA 病人被用作分子的预示的指示物。