141P - Microsatellite instability and its relationship with systemic inflammation as prognostic factors in localised colorectal cancer

Background

Microsatellite instability-high (MSI-H) is a well-known favorable prognostic marker in localized colorectal cancer (CRC) patients, mainly due to local anti-tumor immunity of cytotoxic T cells. The tumor-induced systemic inflammation is also proven to be responsible for pro-tumor immunity. Despite the importance of tumor microenvironment, the relationships between MSI status, systemic inflammation, and their prognostic effects in CRC patients have not been widely studied.

Methods

We retrospectively analyzed a total of 1130 patients who had diagnosed as stage I to III CRC and had surgical resection from Jan 2007 to Oct 2016 at Gil Medical Center in South Korea. MSI status was evaluated by polymerase-chain reaction (PCR) of mononucleotide repeats. Neutrophil-lymphocyte ratio (NLR), from the blood cell count drawn before any treatment, was used to represent systemic inflammation. Univariable and multivariable analysis were performed with Cox’s proportional hazard model to identify prognostic factors in localized CRC patients.

Results

Among 1130 patients of stage I to III CRC, 84 (7.4%) patients had MSI-H CRC, and the majority of MSI-H CRCs were found in stage II patients (12.2%, n=46/378). MSI-H was significantly associated with high NLR (20.2% vs 7.4%, p<0.001) as well as right-sided (67.4% vs 20.9%, p<0.001), poorly differentiated (17.4% vs 2.8%, p<0.001), less perineural invasion (11.6% vs 22.4%, p=0.020), and low BMI (5.8% vs 14.3%, p=0.028). Combining MSI and NLR, MSS/NLR≥5 group showed worst PFS and OS consistently throughout stage I to III (p=0.017). Interestingly, MSI-H/NLR≥5 group showed worse PFS and OS than MSS/NLR<5 group in stage II patients (p=0.006). In multivariable analysis, MSS/NLR≥5 group was related significantly with poor PFS (HR 4.19, 95% CI 1.37-12.83, p=0.012), and showed a trend toward poor OS (HR 4.42, 95% CI 0.84-23.11, p=0.079).

Conclusions

MSI-H was significantly associated with high NLR, and its prognostic effect outweighed that of MSI-H, especially in stage II CRC. Therefore, we should consider more about factors of tumor microenvironment such as high NLR, as one of criteria to classify high-risk stage II CRC, which needs adjuvant chemotherapy.

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.