Department of Pathology, Yale University School of Medicine, New Haven, CT 06520-8023, USA.
Department of Pathology, Yale University School of Medicine, New Haven, CT 06520-8023, USA.
Hum Pathol. 2014 Mar;45(3):549-55. doi: 10.1016/j.humpath.2013.10.022. Epub 2013 Oct 30.
Tissue identity testing by short tandem repeat (STR) polymorphism offers discriminating power in resolving tissue mix-up or contamination. However, one caveat is the presence of microsatellite unstable tumors, in which genetic alterations may drastically change the STR wild-type polymorphism leading to unexpected allelic discordance. We examined how tissue identity testing results can be altered by the presence of microsatellite instability (MSI). Eleven cases of MSI-unstable (9 intestinal and 2 endometrial adenocarcinomas) and 10 cases of MSI-stable tumors (all colorectal adenocarcinomas) were included. All had been previously tested by polymerase chain reaction testing at 5 National Cancer Institute (NCI) recommended MSI loci and/or immunohistochemistry for DNA mismatch repair proteins (MLH1, MSH2, MSH6, and PMS2). Tissue identity testing targeting 15 STR loci was performed using AmpF/STR Identifiler Amplification. Ten of 11 MSI-unstable tumors demonstrated novel alleles at 5 to 12 STR loci per case and frequently with 3 or more allelic peaks. However, all affected loci showed identifiable germline allele(s) in MSI-high tumors. A wild-type allelic profile was seen in 7 of 10 MSI-stable tumors. In the remaining 3 cases, isolated novel alleles were present at a unique single locus in addition to germline alleles. Loss of heterozygosity was observed frequently in both MSI-stable (6/11 cases) and MSI-unstable tumors (8/10 cases). In conclusion, MSI may significantly alter the wild-type allelic polymorphism, leading to potential interpretation errors of STR genotyping. Careful examination of the STR allelic pattern, high index of suspicion, and follow-up MSI testing are crucial to avoid erroneous conclusions and subsequent clinical and legal consequences.
短串联重复序列（STR）多态性的组织同一性检测在解决组织混合或污染方面提供了区分能力。然而，需要注意的是存在微卫星不稳定肿瘤，其中遗传改变可能会极大地改变 STR 野生型多态性，导致意想不到的等位基因不和谐。我们研究了微卫星不稳定性（MSI）的存在如何改变组织同一性检测结果。包括 11 例 MSI 不稳定（9 例肠和 2 例子宫内膜腺癌）和 10 例 MSI 稳定的肿瘤（均为结直肠腺癌）。所有这些肿瘤都已经通过聚合酶链反应检测在 5 个美国国立癌症研究所（NCI）推荐的 MSI 位点进行了测试，或者通过免疫组织化学检测 DNA 错配修复蛋白（MLH1、MSH2、MSH6 和 PMS2）进行了测试。使用 AmpF/STR Identifiler 扩增针对 15 个 STR 位点进行组织同一性检测。11 例 MSI 不稳定肿瘤中的 10 例在每个病例中有 5 到 12 个 STR 位点显示新的等位基因，并且经常有 3 个或更多等位基因峰。然而，所有受影响的位点在 MSI 高肿瘤中都显示出可识别的种系等位基因。在 10 例 MSI 稳定肿瘤中，7 例显示出野生型等位基因谱。在其余 3 例中，除了种系等位基因外，还存在独特单一位点的孤立新等位基因。杂合性丢失在 MSI 稳定（11 例中的 6 例）和 MSI 不稳定肿瘤（10 例中的 8 例）中均频繁发生。总之，MSI 可能会显著改变野生型等位基因多态性，导致 STR 基因分型的潜在解释错误。仔细检查 STR 等位基因模式、高度怀疑和后续 MSI 检测对于避免错误结论和随后的临床和法律后果至关重要。
