Department of Pathology, Seoul National University College of Medicine, 28 Yongon-dong, Songno-gu, Seoul, Korea.
Dis Colon Rectum. 2012 Feb;55(2):181-90. doi: 10.1097/DCR.0b013e31823c46ce.
The contribution of chromosomal instability, microsatellite instability, and epigenetic instability to the development of synchronous colorectal carcinomas is controversial.
This study aimed to investigate the relative roles of microsatellite instability and epigenetic instability in the development of synchronous colorectal cancers.
This was a retrospective study of medical records with histologic, immunohistochemical, and molecular examination of stored tissue samples.
The study took place at Seoul National University Hospital, Korea.
A total of 46 patients with synchronous colorectal cancers and 105 patients with solitary colorectal cancers were included.
Clinicopathologic and molecular characteristics including microsatellite instability, mismatch repair gene expression, CpG island methylator phenotype, and mutation of KRAS and BRAF were analyzed.
Patients with synchronous tumors were more likely to be men than those with solitary tumors and had a tendency toward colocalization of individual tumors in the left or right colon. MSI-deficient cancers were more frequent in synchronous than in solitary cancers. The frequencies of CpG island methylator phenotype-high and KRAS and BRAF mutations were not different between synchronous and solitary cancers. No differences between synchronous cancers and solitary cancers were observed in overall survival or progression-free survival. Within the synchronous cancer group, patients with individual tumors discordant for microsatellite instability status had the worst clinical outcome, whereas those with individual tumors concordant for microsatellite instability-deficient status had the best clinical outcome.
The study was limited by its retrospective nature. Molecular analysis was performed only on cancerous lesions.
Our findings suggest that microsatellite instability plays a more important role than does epigenetic instability in the development of synchronous colorectal cancers, and that information regarding concordant or discordant microsatellite instability status between individual tumors might help to predict clinical outcome of synchronous colorectal cancers.
染色体不稳定性、微卫星不稳定性和表观遗传不稳定性对结直肠同步癌的发生发展的作用仍存在争议。
本研究旨在探讨微卫星不稳定性和表观遗传不稳定性在结直肠同步癌发生发展中的相对作用。
这是一项回顾性的病历研究，对储存的组织样本进行组织学、免疫组织化学和分子检查。
韩国首尔国立大学医院。
共纳入 46 例结直肠同步癌患者和 105 例结直肠单发癌患者。
分析临床病理和分子特征，包括微卫星不稳定性、错配修复基因表达、CpG 岛甲基化表型和 KRAS 和 BRAF 突变。
与单发癌患者相比，同步癌患者中男性更多，且左、右半结肠癌的肿瘤病灶更倾向于聚集。微卫星不稳定性缺失型癌症在同步癌中比单发癌更常见。CpG 岛甲基化表型高和 KRAS 和 BRAF 突变在同步癌和单发癌之间的频率没有差异。同步癌患者的总生存或无进展生存与单发癌患者之间无差异。在同步癌组中，微卫星不稳定性状态不一致的单个肿瘤患者的临床结局最差，而微卫星不稳定性缺失状态一致的单个肿瘤患者的临床结局最好。
本研究受限于回顾性设计。分子分析仅在癌性病变上进行。
我们的研究结果表明，微卫星不稳定性在结直肠同步癌的发生发展中比表观遗传不稳定性更为重要，而单个肿瘤之间微卫星不稳定性状态的一致性或不一致性的信息可能有助于预测结直肠同步癌的临床结局。
