Quang Loc Bui

Objectives: Detecting and diagnosing Lynch syndrome in colorectal cancer patients is essential for enhancing the quality of diagnosis, treatment, and management. This study aims to characterize mismatch repair (MMR) protein expression and MMR gene variants in Vietnamese patients. Methods: A total of 218 patients diagnosed with colorectal cancer at the Nuclear Medicine and Oncology Center, Bach Mai Hospital (Hanoi, Vietnam) were included in this descriptive, retrospective study. Tumor tissue samples were evaluated for MMR protein expression. Cases with loss of MMR protein expression underwent genomic sequencing for MMR gene mutations. Results: Among 218 colorectal cancer patients, 135 were men (61.9 %) and 83 were women (38.1 %), aged 16–86 years. The prevalence of MMR deficiency (dMMR) was 14.7 %. The expression loss rates of the MLH1, MSH2, MSH6, PMS2, MLH1/PMS2, and MSH2/MSH6 proteins were 9.4 %, 3.1 %, 3.1 %, 21.9 %, 46.9 %, and 15.6 %, respectively. Within the dMMR group, four variants were identified in the MLH1 gene, one in the MSH2 gene, two in the PMS2 gene, and one in the EPCAM gene, and all were classified as germline pathogenic variants associated with Lynch syndrome. Conclusion: This is a study to apply next-generation sequencing (NGS) technology to diagnose Lynch syndrome from dMMR cases in Vietnamese colorectal cancer patients. Our research supports the screening and diagnosis of Lynch syndrome through testing using MMR protein expression and assessing pathogenic variants in MMR genes.

Background: Several studies reported improved outcomes with conventional treatments (CT, i.e., chemotherapy ± targeted therapy) administered after immune checkpoints inhibitors (ICI) in certain tumor types. No data are available concerning patients (pts) with metastatic colorectal cancer (mCRC) harboring mismatch repair deficiency/microsatellite instability (dMMR/MSI). We aimed to assess the outcomes of dMMR/MSI mCRC pts receiving CT after ICI failure. Methods: We conducted a retrospective multicenter study investigating the outcomes of all dMMR/MSI mCRC pts who received post-ICI CT between 2015 and 2020. Results: 31 pts (male 61%, median age 56 years) were included. ICI was an anti-PD(L)1 monotherapy in 71% of pts, and 61% received >2 lines before post-ICI CT. The overall response rate and disease control rate were 13% and 45%, with a median progression-free survival (PFS) and overall survival of 2.9 and 7.4 months, respectively. No association of the outcomes with either ICI efficacy or anti-angiogenic agents was observed. Prolonged PFS (range 16.1–21.3 months) was observed in 4 pts (13%). Conclusions: Although conducted on a limited number of patients, our results do not support an association of previous ICI treatment with an enhanced efficacy of CT in dMMR/MSI mCRC. However, prolonged disease control was observed in several cases, suggesting that some pts might derive an unexpected benefit from post-ICI treatments.