Association of microsatellite instability (MSI) status with the 5-year outcome and genetic ancestry in a large Brazilian cohort of colorectal cancer

Gustavo Noriz Berardinelli, Ronílson Durães, Allini Mafra da Costa, Arinilda Bragagnoli, Marco Antônio de Oliveira, Rui Pereira, Cristovam Scapulatempo-Neto, Denise Peixoto Guimarães, Rui Manuel Reis*

*Corresponding author for this work

Research output: Contribution to journalArticleResearchpeer-review

8 Citations (Scopus)

Abstract

Colorectal cancer (CRC) has a high incidence and mortality worldwide. Microsatellite instability (MSI) is crucial in CRC, with distinct molecular and clinicopathological features in patients. Nowadays, it is a predictive marker for immunotherapy. We proposed to evaluate the 5-year outcome of MSI status in 1002 Brazilian CRC, and associate it with genetic ancestry, molecular and clinicopathological features. MSI evaluation was performed using molecular markers. MSI+ tumors were analyzed for alterations in 23 MSI-targeted genes. Genetic ancestry was evaluated using an Ancestry-Informative markers panel. MSI status was analyzed in relation to CRC specific survival and other clinical and genetic variables. MSI+ status was observed in 10.5% of cases. MSI+ status was significantly associated with the anatomic site right colon, mucinous histological type, clinical stage II, histological grade III/undifferentiated, no recurrence of disease, and live cases without cancer. No association of MSI status with genetic ancestry components was observed. MSI-targeted genes analyses showed the most frequently altered genes: ATM, EGFR, MRE11, ROCK1, and TGFBRII. There was a statistically significant difference in cancer-specific survival between cases according to MSI status. This study constitutes the most comprehensive analyses of the MSI impact on the Brazilian CRC. MSI+ frequency in Brazilian CRC agreed with the literature and was associated with several clinicopathological features related with less aggressive tumors, independently of their genetic ancestry.

Original languageEnglish
Pages (from-to)824-832
Number of pages9
JournalEuropean Journal of Human Genetics
Volume30
Issue number7
DOIs
Publication statusPublished - Jul 2022
Externally publishedYes

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