Department of Haematology and Oncological Sciences L. and A. Seragnoli, Section of Anatomic Pathology at Bellaria Hospital, University of Bologna, via Altura 3, 40139 Bologna, Italy.
Int J Colorectal Dis. 2012 May;27(5):647-56. doi: 10.1007/s00384-011-1365-7. Epub 2011 Nov 23.
Stratifying patients defective in mismatch repair (dMMR) with high microsatellite instability (MSI-H) in colorectal cancer (CRC) is of increasing relevance and may provide a more tailored approach to CRC adjuvant therapy. Here, we describe the discovery of a new MSI marker for colorectal cancer located in the 3'-untranslated region (3'UTR, T20 mononucleotide repeat) of the metallothionein 1X gene (MT1XT20).
We studied 340 consecutive CRCs using three multiplexed polymerase chain reactions amplifying BAT25, BAT26, TGFBR2, MybT22, BAT40, MT1XT20, NR21, NR24, CAT25, D2S123, D5S346, D17S250, D18S58, CSF1PO, D7S820, and D18S51. Fragments length was evaluated by automated capillary electrophoresis.
Based on the NCI/ICG-HNPCC criteria for MSI classification, 40 CRCs were found to be MSI-high (11.8%), 46 (13.5%) CRCs were MSI-low, and 254 CRCs (74.7%) were stable (MSS). MT1XT20 showed very high sensitivity (97.3%) comparable to BAT26 (97.5%) and CAT25 (97.1%) and the best specificity (100%) as well as MybT22 and CAT25. Indeed, MT1XT20 instability was detected in 36 out of 37 cases (97.3%) of MSI-high colorectal cancers, whereas no MT1XT20 alterations were observed in 254 MSS or in 46 MSI-low cases. On the contrary, BAT40 was found to be unstable in 8/46 MSI-low cases, BAT25 in 6/46, BAT26 4/46, NR21 1/46, and NR24 in 1/45.
Our results suggest that MT1XT20 represents a sensitive and specific marker for MSI testing and could be included in a complete set of MSI markers for the confident identification of familial or sporadic dMMR patients in CRCs.
在结直肠癌（CRC）中对存在错配修复缺陷（dMMR）和高微卫星不稳定性（MSI-H）的患者进行分层，这一点变得越来越重要，并且可能为 CRC 辅助治疗提供更具针对性的方法。在这里，我们描述了一种新的 MSI 标记物的发现，该标记物位于金属硫蛋白 1X 基因（MT1XT20）的 3'-非翻译区（3'UTR，T20 单核苷酸重复），用于结直肠癌。
我们使用三种多重聚合酶链反应研究了 340 例连续的 CRC，这些反应扩增了 BAT25、BAT26、TGFBR2、MybT22、BAT40、MT1XT20、NR21、NR24、CAT25、D2S123、D5S346、D17S250、D18S58、CSF1PO、D7S820 和 D18S51。通过自动毛细管电泳评估片段长度。
根据 MSI 分类的 NCI/ICG-HNPCC 标准，发现 40 例 CRC 为 MSI-高（11.8%），46 例（13.5%）CRC 为 MSI-低，254 例（74.7%）为稳定（MSS）。MT1XT20 显示出非常高的灵敏度（97.3%），与 BAT26（97.5%）和 CAT25（97.1%）相当，特异性最好（100%），与 MybT22 和 CAT25 相当。事实上，在 37 例 MSI-高结直肠癌中检测到 36 例（97.3%）MT1XT20 不稳定，而在 254 例 MSS 或 46 例 MSI-低病例中未观察到 MT1XT20 改变。相反，在 46 例 MSI-低病例中发现 BAT40 不稳定 8 例，BAT25 不稳定 6 例，BAT26 不稳定 4 例，NR21 不稳定 1 例，NR24 不稳定 1 例。
我们的结果表明，MT1XT20 是一种用于 MSI 检测的敏感和特异的标志物，并且可以包含在一套完整的 MSI 标志物中，用于在 CRC 中自信地识别家族性或散发性 dMMR 患者。
