The differences between suspicious Lynch and sporadic dMMR colorectal cancers

Background

Few studies have systematically compared the difference between germline and sporadic dMMR colorectal cancers on clinical-pathological features, prognosis, lymphocytic reactions, somatic mutation frequencies and neoantigen burdens.

Methods

We retrospectively collected dMMR colorectal patients identified by postoperative immunohistochemistry screening. According to genetic test or clinical-pathological criterias, patients were then grouped as suspicious Lynch or sporadic dMMR. We compared the clinico-pathologic and prognostic differences between the two groups. By evaluating the four components of lymphocytic reaction {i.e., Crohn's-like reaction (CRO), immunoreactions in the invasive margin (IM), in the tumour stroma (TS) and cancer center (CC)} and counting CD3 + /CD4 + /CD8 + /Foxp3+ tumor-infiltrating lymphocytes, we investigated their immune response and lymphocyte subgroup differences. By whole exome sequencing and neoantigen detection pipeline, we contrasted their discrepancies on mutational frequencies and neoantigen burdens.

Results

213 of the 381 dMMR pts were grouped: 94 sporadic dMMR and 119 suspicious Lynch. Sporadic dMMR patients were significantly older (P 

Conclusions

There were more somatic mutations and neoantigens in suspicious Lynch patients and causing their more intense immunoreactions, which might benefit their survival.

Clinical trial identification

No

Legal entity responsible for the study

Sun Yat-sen University Cancer Center

Funding

Nature Science Foundation of China (Grant number: 81101591).

Disclosure

All authors have declared no conflicts of interest.