Sakurai Masato, Zhao Yan, Oki Eiji, Kakeji Yoshihiro, Oda Shinya, Maehara Yoshihiko
Department of Surgery and Science, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan.
Eur J Gastroenterol Hepatol. 2007 Aug;19(8):701-9. doi: 10.1097/MEG.0b013e3281ac20a8.
Microsatellite instability (MSI) is associated with various human malignancies and regarded as reflecting cellular deficiency in DNA mismatch repair (MMR). Analysis of MSI has been prevalent in the field of oncology, and numerous data have accumulated in the literature. It has been reported that the MSI+ phenotype is relatively frequent in gastric cancer. The reported frequencies of MSI+ gastric tumors, however, are diverse.
To determine the frequencies of the MSI+ phenotype and defective MMR in gastric cancer, we examined tumors derived from 167 patients with sporadic gastric cancer, using our unique fluorescent technique, 'high-resolution fluorescent microsatellite analysis'.
High-resolution fluorescent microsatellite analysis allowed us the unequivocal designation of MSI. The frequencies of MSI-H and MSI-L were 11 and 9.6%, respectively. In addition to the distinction based on the frequency of microsatellite changes, MSI was classifiable into two distinct categories, type A and type B, according to the mode of length changes in the dinucleotide microsatellites. Type A and type B MSI were observed in 14 and 6.6%, respectively. The overall frequency of MSI was 21%. Intriguingly, MSI did not correlate with any of commonly used clinicopathological variables. In addition, neither MSI-H nor MSI-L correlated with family history of malignancies or patient history of multiple cancers. Instead, type B MSI was significantly more frequent in patients with family history of gastric cancer. Type A MSI appeared to occur more frequently in tumors of patients with a history of double cancer, which, however, was not statistically significant.
In gastric cancer, contribution of defective MMR to the risk of multiple cancer or familial predisposition appears more limited than has been expected. The relationship between MSI and high risk of cancer may have been oversimplified, at least in gastric cancer.
微卫星不稳定性（MSI）与多种人类恶性肿瘤相关，被认为反映了DNA错配修复（MMR）中的细胞缺陷。MSI分析在肿瘤学领域已很普遍，文献中积累了大量数据。据报道，MSI+表型在胃癌中相对常见。然而，报道的MSI+胃癌肿瘤的频率各不相同。
为了确定胃癌中MSI+表型和MMR缺陷的频率，我们使用独特的荧光技术“高分辨率荧光微卫星分析”，检测了167例散发性胃癌患者的肿瘤。
高分辨率荧光微卫星分析使我们能够明确地确定MSI。MSI-H和MSI-L的频率分别为11%和9.6%。除了根据微卫星变化频率进行区分外，根据二核苷酸微卫星长度变化的模式，MSI可分为两种不同类型，A 型和 B 型。分别在14%和6.6%的病例中观察到 A 型和 B 型MSI。MSI的总体频率为21%。有趣的是，MSI与任何常用的临床病理变量均无相关性。此外，MSI-H和MSI-L均与恶性肿瘤家族史或多癌患者病史无关。相反，B型MSI在有胃癌家族史的患者中明显更常见。A型MSI似乎在有双癌病史患者的肿瘤中更频繁出现，然而，这在统计学上并不显著。
在胃癌中，MMR缺陷对多癌风险或家族易感性的影响似乎比预期的更有限。至少在胃癌中，MSI与癌症高风险之间的关系可能被过度简化了。
