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Familial Cancer

, Volume 17, Issue 3, pp 395–402 | Cite as

Universal determination of microsatellite instability using BAT26 as a single marker in an Argentine colorectal cancer cohort

  • María Laura GonzálezEmail author
  • Natalia Causada-Calo
  • Juan Pablo Santino
  • Mev Dominguez-Valentin
  • Fabiana Alejandra Ferro
  • Inés Sammartino
  • Pablo Germán Kalfayan
  • Maria Alicia Verzura
  • Tamara Alejandra Piñero
  • Andrea Romina Cajal
  • Walter Pavicic
  • Carlos Vaccaro
Original Article
  • 179 Downloads

Abstract

Microsatellite instability (MSI) is a hallmark tool for Lynch syndrome (LS) screening and a prognostic marker for sporadic colorectal cancer (CRC). In regions with limited resources and scarce CRC molecular characterization as South America, the implementation of universal MSI screening is under debate for both its purposes. We sought to estimate the frequency of BAT26 in colorectal adenocarcinomas and to determine associated clinical and histological features. Consecutive patients from a CRC registry were included. BAT26 determination was performed in all cases; if instability was found, immunohistochemistry (IHC) and BRAF mutation analyses were done, as appropriate. Differences were assessed by chi-squared or Fisher’s exact test, or by T test or Mann–Whitney. Multiple logistic regression was used to identify factors independently associated with BAT26-unstable tumors. We included 155 patients; mean age was 65.6 (SD 14.4) and 56.1% were male. The frequency of BAT26-unstable tumors was 22% (95% CI 15.7–29.3). Factors independently associated with BAT26-unstable tumors were right colon localization (OR 3.4, 95% CI 1.3–8.7), histological MSI features (OR 5.1, 95% CI 1.9–13.6) and Amsterdam criteria (OR 23.2, 95% CI 1.9–286.7). IHC was altered in 85.3% BAT26-unstable tumors and 70.6% lacked MLH1 expression; 47.8% of these harbored BRAF V600E mutation. We provide evidence to link the frequency of BAT26 to an increased diagnostic yield (up to 1.4-folds) of suspected LS cases in comparison to the revised Bethesda guidelines alone. In regions with limited resources, clinical and histological features associated with BAT26-unstable status could be useful to direct MSI screening in sporadic CRCs and may help guide clinical care and future research.

Keywords

Microsatellite instability BAT26 Colorectal cancer Lynch syndrome Universal screening 

Notes

Acknowledgements

The authors would like to thank all members of the ProCanHe group and patients from the CRC Registry.

Author contributions

MLG: concept and design, data interpretation, manuscript writing and scientific discussion. NCC: statistical analysis and data interpretation, manuscript writing. JPS: histopathological and IHQ analysis. MDV: contributed to manuscript writing and scientific discussion. FAF and IS: data collection. PGK and MAV: scientific discussion. TAP and ARC: BAT26 and BRAF V600E determination. CV: concept and design, manuscript revision and scientific discussion.

Compliance with ethical standards

Conflict of interest

María L. González and Carlos Vaccaro received a grant from the Instituto Nacional del Cáncer, Argentina. The remaining authors declare no conflict of interest.

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Copyright information

© Springer Science+Business Media B.V. 2017

Authors and Affiliations

  • María Laura González
    • 1
    • 2
    Email author
  • Natalia Causada-Calo
    • 1
    • 2
    • 3
  • Juan Pablo Santino
    • 1
    • 5
  • Mev Dominguez-Valentin
    • 4
  • Fabiana Alejandra Ferro
    • 1
  • Inés Sammartino
    • 1
  • Pablo Germán Kalfayan
    • 1
  • Maria Alicia Verzura
    • 1
  • Tamara Alejandra Piñero
    • 1
    • 7
  • Andrea Romina Cajal
    • 1
    • 7
  • Walter Pavicic
    • 1
  • Carlos Vaccaro
    • 1
    • 6
  1. 1.Programa de Cáncer Hereditario (ProCanHe), Hospital Italiano de Buenos AiresBuenos AiresArgentina
  2. 2.Gastroenterology DepartmentHospital Italiano de Buenos AiresBuenos AiresArgentina
  3. 3.Department of Medicine, Farncombe Family Digestive Research InstituteMcMaster UniversityHamiltonCanada
  4. 4.Department of Tumor Biology, Institute for Cancer ResearchThe Norwegian Radium HospitalOsloNorway
  5. 5.Pathology DepartmentHospital Italiano de Buenos AiresBuenos AiresArgentina
  6. 6.Surgery DepartmentHospital Italiano de Buenos AiresBuenos AiresArgentina
  7. 7.Instituto Universitario, Hospital Italiano de Buenos AiresBuenos AiresArgentina

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