Abstract 377P
Background
Tumor DNA mismatch repair (MMR) deficiency testing has become an indispensable test in metastatic colorectal cancer (mCRC) due to the high efficacy of immunotherapy in patients with deficient MMR (dMMR) status. However, a significant portion of dMMR CRC tumors exhibit primary or acquired resistance. Heterogeneous MMR status may associate with refractoriness to immunotherapy. We aimed to study the concordance in MMR status between primary and paired metastasis in mCRC.
Methods
Our study included 84 mCRC patients with both primary and matched metastatic sites. Immunohistochemistry was used to determine the MMR patterns of primary lesions and metastases. A pooled analysis including 913 cases was used to determine the frequency and organ-specific heterogeneity of MMR status. The relationship between MMR phenotype heterogeneity and clinical outcomes was investigated.
Results
10 (11.9%) of the patients had MMR status heterogeneity between primary and metastatic tumours. Prevalence of heterogeneous MMR patterns is significantly higher in patients with dMMR primary tumors than patients with proficient MMR (pMMR) primary tumors and which was also verified in the pooled analysis (P<0.001). MMR status discordance between primary and metastatic tumours was more common in patients with peritoneal metastases (10.67%). For the patients with dMMR primary tumours, the discrepancy regarding MMR status was observed in patients with liver, lung, ovary, peritoneum, and distant lymph node metastasis. For the patients with pMMR primary tumours, the discrepancy was more likely to be limited to liver ((26/440) or peritoneal (7/112) metastasis (P=0.02).The patients with isolated heterogeneous expression of MSH6 and PMS2, as well as paired heterogeneous expression of MSH2/MSH6 and MLH1/PMS2, were relatively higher. Patients with MMR status heterogeneity or not had comparable OS (P=0.452).
Conclusions
Heterogeneous MMR patterns exist in a subset of mCRC patients, especially in patients with dMMR primary tumors. Testing the metastatic site might be valuable in cases of peritoneal metastasis as the discordance of MMR status potentially could affect immune surveillance and immunotherapy.
Clinical trial identification
Editorial acknowledgement
Legal entity responsible for the study
The authors.
Funding
Has not received any funding.
Disclosure
All authors have declared no conflicts of interest.