Phenotypic attributes and survival in mismatch repair deficient/microsatellite instability-high colorectal carcinomas

Abstract

BACKGROUND

Mismatch repair deficient/microsatellite instability-high (MMR-D/MSI-H) colorectal cancers (CRCs) possess a distinctive genomic profile that results in a spectrum of phenotypic attributes setting them apart from their mismatch repair proficient (MMR-P) or microsatellite stable (MSS) counterparts. CRCs have several prognostic factors, including stage, tumor differentiation, location, lymphovascular and perineural invasion, tumor budding, tumor infiltrating lymphocytes, lymph node yield (LNY), and lymph node ratio (LNR).

AIM

To determine the unique phenotypic characteristics of MMR-D/MSI-H CRCs and leverage the conventional wisdom of LNY and LNR with the distinctive characteristics of MMR-D/MSI-H CRCs.

METHODS

This retrospective analysis involved 223 stage I-III CRC patients who underwent surgical resection without neoadjuvant treatment. Clinical and histological features were obtained from patient records and by re-examining the hematoxylin and eosin-stained slides. MMR/MSI status was evaluated for all patients using either MMR immunohistochemistry or MSI testing.

RESULTS

Of the 223 patients in our study, 87 (39.01%) were MMR-D/MSI-H CRCs while 136 (60.99%) were MMR-P/MSS CRCs. The MMR-D/MSI-H CRCs exhibited significant statistical differences compared to the MMR-P/MSS CRCs in several factors, including location, stage, tumor budding, lymphovascular and perineural invasion, lymphocytic response, LNY, LNR, and size of uninvolved lymph nodes. LNY and LNR were significantly higher in MMR-D/MSI-H group compared with the MMR-P/MSS group (P = 0.003 and P < 0.001, respectively). Also, the interquartile range of the largest uninvolved lymph node was 1 cm (0.8 cm-1.2 cm) in MMR-D/MSI-H CRCs compared to 0.7 cm (0.6 cm-0.97 cm) in MMR-P/MSS CRCs. The overall survival for the MMR-P/MSS CRC group was 71% at five years, and the MMR-D/MSI-H CRC group was 92% at five years (P < 0.001).

CONCLUSION

MMR-D/MSI-H CRCs possess a unique genomic profile that leads to distinct phenotypic characteristics, including an enhanced immune response. This distinctive profile underscores the substantial prognostic and predictive value of MMR-D/MSI-H status in CRC.

Keywords: Mismatch repair; Microsatellite instability; Lymph node yield; Lymph node ratio; Colorectal carcinoma

Core Tip: Mismatch repair deficient/microsatellite instability-high (MMR-D/MSI-H) colorectal cancers (CRCs) account for 15% of CRCs exhibiting peculiar clinicopathological features. The correlation between MMR-D/MSI-H status and distinct lymph node characteristics, including increased lymph node yield, low lymph node ratio, and larger uninvolved node size, suggests a potential link to the heightened immune response typical of these cancers. These findings reinforce the promising prognosis associated with MMR-D/MSI-H CRC, reflecting improved overall survival rates compared to mismatch repair proficient or microsatellite stable tumors and offering valuable insights for tailored therapeutic approaches in this specific subtype of CRC.