Microsatellite Status Detection in Gastrointestinal Cancers: PCR/NGS Is Mandatory in Negative/Patchy MMR Immunohistochemistry

胃肠道癌症中的微卫星状态检测:PCR/NGS 是阴性/不规则 MMR 免疫组织化学检测中的必需步骤

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作者:Federica Zito Marino, Martina Amato, Andrea Ronchi, Iacopo Panarese, Franca Ferraraccio, Ferdinando De Vita, Giuseppe Tirino, Erika Martinelli, Teresa Troiani, Gaetano Facchini, Felice Pirozzi, Michele Perrotta, Pasquale Incoronato, Raffaele Addeo, Francesco Selvaggi, Francesco Saverio Lucido, Miche

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.

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.

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

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.

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