Abstract 462P
Background
Deficient mismatch repair system (dMMR)/microsatellite instability (MSI) is found in about 5% of metastatic colorectal cancers (mCRCs). dMMR/MSI status has a major therapeutic impact for immune checkpoints inhibitors use in metastatic setting. Small case studies have reported discrepancies in dMMR/MSI status between primary tumor and metastases in mCRCs.
Methods
We conducted a retrospective multicenter study including all consecutive patients with a dMMR/MSI CRC and at least one available metastatic tumor sample. 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 tumors and matched metastases.
Results
We included 99 patients with a dMMR/MSI mCRC with 98 primary tumor samples and 117 metastatic tumor samples (liver: 28, peritoneum: 54, lung: 5 and others: 30). For all 215 samples MMR IHC and/or molecular MSI tests were performed and 91.2% had both tests. Only 4 discrepancies (1.9%) with a dMMR/MSI primary CRC and a pMMR/MSS metastasis were initially identified. Expert pathologists and molecular biologists extensively reviewed these discordant cases. Two cases were false discrepancies: one with two synchronous primary CRC (dMMR/MSI and pMMR/MSS) and one with pMMR/MSS peritoneal metastasis that was not confirmed after pathological proofreading (atypical mesothelial hyperplasia). Another discordant case with a dMMR/MSI primary CRC and MSS peritoneal metastasis could not be confirmed due to the low level of tumor cells. The last case had a confirmed discrepancy with a dMMR/MSI primary CRC and a pMMR/MSS peritoneal metastasis.
Conclusions
Our study demonstrated a high concordance rate of dMMR/MSI status between primary CRCs and their metastases. Most discrepancies were explained by human or technical errors and must be reviewed. Analysis of one sample, either from primary tumor or metastasis, with consistent dMMR/MSI status seems enough prior treatment with immune checkpoint inhibitors.
Clinical trial identification
Editorial acknowledgement
Legal entity responsible for the study
Pr David Tougeron.
Funding
Has not received any funding.
Disclosure
D. Tougeron: Financial Interests, Personal, Advisory Board: Amgen; MSD; Pierre Fabre; Non-Financial Interests, Personal, Other, Congress: Merck; Roche; Financial Interests, Personal, Sponsor/Funding: Bayer; Ipsen. G. Tachon: Financial Interests, Personal, Invited Speaker: AstraZeneca; Financial Interests, Personal, Training: Roche; Pfizer. D. Sefrioui: Financial Interests, Personal, Advisory Board: Servier; Ipsen; Financial Interests, Personal, Principal Investigator: Astellas; Financial Interests, Personal, Training: Roche. A. Zaanan: Financial Interests, Personal, Invited Speaker: Merck; Pierre Fabre; Financial Interests, Personal, Advisory Board: Baxter; Havas Life; Financial Interests, Personal, Principal Investigator: Amgen; Roche. T. Aparicio: Non-Financial Interests, Personal, Other, Congress: Roche; Financial Interests, Personal, Advisory Board: Sirtec; Financial Interests, Personal, Invited Speaker: Sanofi; Amgen. V. Randrian: Financial Interests, Personal, Invited Speaker: Amgen. R. Guimbaud: Financial Interests, Personal, Invited Speaker: Ipsen; Pierre Fabre; Financial Interests, Personal, Advisory Board: AstraZeneca; MSD; Financial Interests, Personal, Principal Investigator: BMS; Incyte. E. Standley: Financial Interests, Personal, Funding: Fondation pour la recherche medicale. T. Lecomte: Financial Interests, Personal, Advisory Board: Amgen; Servier; Financial Interests, Personal, Invited Speaker: Sanofi; Non-Financial Interests, Personal, Other, Congress: Amgen. L. Karayan Tapon: Financial Interests, Personal, Invited Speaker: AstraZeneca. C. Evrard: Financial Interests, Personal, Other, Congress: Pfizer; Amgen; Financial Interests, Personal, Invited Speaker: Merck. All other authors have declared no conflicts of interest.