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

European Journal of Human Genetics volume 30, pages 824–832 (2022)Cite this article

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A Comment to this article was published on 21 June 2022

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.

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Fig. 1: Genetic ancestry analysis.
Fig. 2: MSI-target gene analyses.

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Data availability

Data supporting the results reported in this manuscript can be found within the article and its Supplementary Files.

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Acknowledgements

The authors acknowledge Dr. Adriane Feijó and Dr. Luciane Sussuchi for their assistance in preparing the figures.

Funding

This study was partially supported by Barretos Cancer Hospital Internal Research Funds (PAIP) of participant authors and the Public Ministry of Labor – Campinas, São Paulo (Research, Prevention, and Education of Occupational Cancer). RMR was the recipient of a National Council of Technological and Scientific Development (CNPq) scholarship. AMC had financial support from the São Paulo Government (São Paulo Research Foundation – FAPESP) through the grants numbers 2019/21722–0 and 2018/22097–0.

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Authors and Affiliations

  1. Molecular Oncology Research Center, Barretos Cancer Hospital, Barretos, São Paulo, Brazil

    Gustavo Noriz Berardinelli, Ronílson Durães, Cristovam Scapulatempo-Neto, Denise Peixoto Guimarães & Rui Manuel Reis

  2. Molecular Diagnostic Laboratory, Barretos Cancer Hospital, Barretos, São Paulo, Brazil

    Gustavo Noriz Berardinelli & Rui Manuel Reis

  3. Department of Oncology, Barretos Cancer Hospital, Barretos, São Paulo, Brazil

    Ronílson Durães & Arinilda Bragagnoli

  4. Population-based Cancer Registry of Barretos Region, Barretos Cancer Hospital, Barretos, São Paulo, Brazil

    Allini Mafra da Costa

  5. Nucleus of Epidemiology and Biostatistics, Barretos Cancer Hospital, Barretos, São Paulo, Brazil

    Marco Antônio de Oliveira

  6. IPATIMUP – Instituto de Patologia e Imunologia Molecular da Universidade do Porto, Porto, Portugal

    Rui Pereira

  7. i3S - Instituto de Investigação e Inovação em Saúde, Universidade do Porto, Porto, Portugal

    Rui Pereira

  8. Department of Endoscopy, Barretos Cancer Hospital, Barretos, São Paulo, Brazil

    Denise Peixoto Guimarães

  9. Life and Health Sciences Research Institute, University of Minho, Gualtar Campus, 4710-057, Braga, Portugal

    Rui Manuel Reis

  10. ICVS/3B’s-PT Government Associate Laboratory, Gualtar Campus, 4710-057, Braga/Guimarães, Portugal

    Rui Manuel Reis

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  1. Gustavo Noriz Berardinelli
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Contributions

GNB participated in study design, collection of the data, analyzed the data, and prepared the manuscript. RD participated in the collection of the clinical data and analyzed the data. AMC participated in the collection of the data and analyzed the data. AB participated in re-evaluation of the clinical data and analyzed the data. MO participated in the statistical analyses and analyzed the data. RP participated in the ancestry analyses and analyzed the data. CS-N participated in the collection of the data and re-evaluation of the diagnoses. DPG participated in re-evaluation of the diagnoses and analyzed the data. RMR participated in study design, coordination, analyses of the data, and prepared the manuscript. All authors read and approved the final manuscript.

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Correspondence to Rui Manuel Reis.

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The study was evaluated and approved by Institutional Ethics Committee (protocol number: 600/2012 - CAAE: 02468812.30000.5437).

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Berardinelli, G.N., Durães, R., Mafra da Costa, A. et al. Association of microsatellite instability (MSI) status with the 5-year outcome and genetic ancestry in a large Brazilian cohort of colorectal cancer. Eur J Hum Genet 30, 824–832 (2022). https://doi.org/10.1038/s41431-022-01104-y

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