Impact of DNA mismatch repair proteins deficiency on number and ratio of lymph nodal metastases in colorectal adenocarcinoma

Background: Approximately 15 % of colorectal adenocarcinomas (CRCs) are characterized by an altered expression of DNA mismatch repair (MMR) proteins (i.e. MMR deficiency [MMRd]). Lymph node ratio (LNR) represents one of the most important prognostic markers in non-advanced CRCs. No significant data are available regarding LNR distribution depending on MMR status.Purpose of the study: The aim of the present work was to compare pathological and clinical characteristics of MMRd tumors versus MMR proficient (MMRp) cases. Particular attention was paid to how these molecular sub-groups relate to the LNR.Materials and methods: A mono-Institutional series of 1037 consecutive surgically treated stage I-IV CRCs were retrospectively selected and data were obtained from pathological reports. Cases were characterized for MMR/ MSI status by means of immunohistochemistry or for microsatellite instability (MSI) analysis.Results: MMRd/MSI tumors (n = 194; 18.7 %) showed significant differences in comparison to MMRp lesions for sex (female prevalence 50.5 % vs 40.7 %; p = 0.013), age (74.2 vs 69.2; p < 0.001), location (right side; p < 0.001), diameter (larger than MMRp; p < 0.001), growth pattern (expansive pattern of growth; p < 0.001), peri-(p = 0.0002) and intra-neoplastic (p = 0.0018) inflammatory infiltrate, presence of perineural invasion (p < 0.001), stage (lower stage at presentation; p < 0.001), grade (higher prevalence of high-grade tumors; p < 0.001), and LNR (lower; p < 0.001).Conclusions: MMRd/MSI tumors are a distinct molecular CRC subtype characterized by a significantly lower LNR in comparison to MMRp lesions. These data further support the prognostic impact of MMRd/MSI status in early-stage CRCs.

Automated summary

This study aimed to compare the pathological and clinical characteristics of MMR-deficient (MMRd) tumors and MMR proficient (MMRp) cases, with a particular focus on the relationship between these molecular subgroups and lymph node ratio (LNR). The study found significant differences between MMRd and MMRp tumors in terms of sex, age, size, growth pattern, inflammatory infiltrate, perineural invasion, stage, grade, and LNR. In conclusion, MMRd tumors are a distinct molecular subtype of colorectal cancer characterized by a significantly lower LNR, further supporting the prognostic impact of MMRd status in early-stage CRC.