胃肠道癌症中的微卫星状态检测：在错配修复蛋白免疫组化结果为阴性/局灶性的情况下，聚合酶链反应/二代测序是必需的
Microsatellite Status Detection in Gastrointestinal Cancers: PCR/NGS Is Mandatory in Negative/Patchy MMR Immunohistochemistry.
作者信息
Zito Marino Federica, Amato Martina, Ronchi Andrea, Panarese Iacopo, Ferraraccio Franca, De Vita Ferdinando, Tirino Giuseppe, Martinelli Erika, Troiani Teresa, Facchini Gaetano, Pirozzi Felice, Perrotta Michele, Incoronato Pasquale, Addeo Raffaele, Selvaggi Francesco, Lucido Francesco Saverio, Caraglia Michele, Savarese Giovanni, Sirica Roberto, Casillo Marika, Lieto Eva, Auricchio Annamaria, Cardella Francesca, Docimo Ludovico, Galizia Gennaro, Franco Renato
机构信息
Pathology Unit, Department of Mental and Physical Health and Preventive Medicine, University of Campania "L. Vanvitelli", 80138 Naples, Italy.
Department of Precision Medicine, University of Campania "L. Vanvitelli", 80138 Naples, Italy.
出版信息
Cancers (Basel). 2022 Apr 28;14(9):2204. doi: 10.3390/cancers14092204.
BACKGROUND
Microsatellite instability (MSI) is a predictive biomarker for immune checkpoint inhibitors. The main goal was to investigate the discordance between IHC and PCR/NGS for MSI testing in gastrointestinal cancers.
METHODS
Two series were analyzed through IHC for mismatch-repair-system proteins (MMRP) and PCR, with one series of 444 colorectal cancers (CRC) and the other of 176 gastric cancers (GC). All cases with discordant results between IHC and PCR were analyzed by NGS. IHC staining was evaluated as follows: proficient MMR (pMMR), with all MMR positive; deficient MMR (dMMR), with the loss of one heterodimer; and cases with the loss/patchy expression of one MMR (lo-paMMR). Cases with instability in at least two markers by PCR were MSI-high (MSI-H) and with instability in one marker, MSI-low (MSI-L). Cases without instability were evaluated as microsatellite-stable (MSS).
RESULTS
In the CRC cohort, 15 out of 444 cases were dMMR and 46 lo-paMMR. Among the 15 dMMR, 13 were MSI-H and 2 MSS. Among the 46 lo-paMMR, 13 were MSI-H and 33 were MSS. In the GC cohort, 13 out of 176 cases were dMMR and 6 cases lo-paMMR. Among the 13 dMMR, 12 were MSI-H and only 1 was MSS. All six lo-paMMR cases were MSS. All NGS results were in agreement with PCR.
CONCLUSIONS
In clinical practice, MMR-IHC could be used as a screening test and additional molecular analysis is mandatory exclusively in cases carrying loss/patchy MMR-IHC.
背景
微卫星不稳定性（MSI）是免疫检查点抑制剂的一种预测性生物标志物。主要目的是研究免疫组化（IHC）与聚合酶链反应（PCR）/二代测序（NGS）在胃肠道癌症MSI检测中的不一致性。
方法
通过免疫组化检测错配修复系统蛋白（MMRP）并结合聚合酶链反应对两个系列进行分析，一个系列为444例结直肠癌（CRC），另一个系列为176例胃癌（GC）。对免疫组化和聚合酶链反应结果不一致的所有病例进行二代测序分析。免疫组化染色评估如下：错配修复功能完整（pMMR），所有错配修复蛋白均为阳性；错配修复功能缺陷（dMMR），有一个异二聚体缺失；以及有一个错配修复蛋白缺失/斑驳表达的病例（lo-paMMR）。聚合酶链反应显示至少两个标记不稳定的病例为微卫星高度不稳定（MSI-H），一个标记不稳定的病例为微卫星低度不稳定（MSI-L）。无不稳定情况的病例评估为微卫星稳定（MSS）。
结果
在结直肠癌队列中，444例病例中有15例为dMMR，46例为lo-paMMR。在15例dMMR病例中，13例为MSI-H，2例为MSS。在46例lo-paMMR病例中，13例为MSI-H，33例为MSS。在胃癌队列中，176例病例中有13例为dMMR，6例为lo-paMMR。在13例dMMR病例中，12例为MSI-H，仅1例为MSS。所有6例lo-paMMR病例均为MSS。所有二代测序结果均与聚合酶链反应结果一致。
结论
在临床实践中，MMR免疫组化可作为一种筛查试验，仅在存在MMR免疫组化缺失/斑驳的病例中必须进行额外的分子分析。
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