Heterogeneity of Mismatch Repair Status and Microsatellite Instability between Primary Tumour and Metastasis and Its Implications for Immunotherapy in Colorectal Cancers |
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Authors: | Camille Evrard,Sté phane Messina,David Sefrioui,É ric Frouin,Marie-Luce Auriault,Romain Chautard,Aziz Zaanan,Marion Jaffrelot,Christelle De La Fouchardiè re,Thomas Aparicio,Romain Coriat,Julie Godet,Christine Silvain,Violaine Randrian,Jean-Christophe Sabourin,Rosine Guimbaud,Elodie Miquelestorena-Standley,Thierry Lecomte,Valé rie Moulin,Lucie Karayan-Tapon,Gaë lle Tachon,David Tougeron |
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Abstract: | Deficient mismatch repair system (dMMR)/microsatellite instability (MSI) is found in about 5% of metastatic colorectal cancers (mCRCs) with a major therapeutic impact for immune checkpoint inhibitor (ICI) use. We conducted a multicentre study including all consecutive patients with a dMMR/MSI mCRC. MSI status was determined using the Pentaplex panel and expression of the four MMR proteins was evaluated by immunohistochemistry (IHC). The primary endpoint was the rate of discordance of dMMR/MSI status between primary tumours and paired metastases. We included 99 patients with a dMMR/MSI primary CRC and 117 paired metastases. Only four discrepancies (3.4%) with a dMMR/MSI primary CRC and a pMMR/MSS metastasis were initially identified and reviewed by expert pathologists and molecular biologists. Two cases were false discrepancies due to human or technical errors. One discordant case could not be confirmed due to the low level of tumour cells. The last case had a confirmed discrepancy with a dMMR/MSI primary CRC and a pMMR/MSS peritoneal metastasis. Our study demonstrated a high concordance rate of dMMR/MSI status between primary CRCs and their metastases. The analysis of one sample, either from the primary tumour or metastasis, with consistent dMMR and MSI status seems to be sufficient prior to treatment with ICI. |
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Keywords: | colorectal cancer microsatellite instability deficient mismatch repair immunohistochemistry inter-tumoral heterogeneity |
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