Characterization and clinical outcomes of DNA mismatch repair-deficient small bowel adenocarcinoma Journal Article


Authors: Latham, A.; Shia, J.; Patel, Z.; Reidy-Lagunes, D. L.; Segal, N. H.; Yaeger, R.; Ganesh, K.; Connell, L.; Kemeny, N. E.; Kelsen, D. P.; Hechtman, J. F.; Nash, G. M.; Paty, P. B.; Zehir, A.; Tkachuk, K. A.; Sheikh, R.; Markowitz, A. J.; Mandelker, D.; Offit, K.; Berger, M. F.; Cercek, A.; Garcia-Aguilar, J.; Saltz, L. B.; Weiser, M. R.; Stadler, Z. K.
Article Title: Characterization and clinical outcomes of DNA mismatch repair-deficient small bowel adenocarcinoma
Abstract: Purpose: The prevalence and clinical characteristics of small bowel adenocarcinomas (SBA) in the setting of Lynch syndrome have not been well studied. We characterized SBA according to DNA mismatch repair and/or microsatellite instability (MMR/MSI) and germline mutation status and compared clinical outcomes. Experimental Design: A single-institution review identified 100 SBAs. Tumors were evaluated for MSI via MSIsensor and/or corresponding MMR protein expression via IHC staining. Germline DNA was analyzed for mutations in known cancer predisposition genes, including MMR (MLH1, MSH2, MSH6, PMS2, and EPCAM). Clinical variables were correlated with MMR/MSI status. Results: Twenty-six percent (26/100; 95% confidence interval, 18.4-35.4) of SBAs exhibited MMR deficiency (MMR-D). Lynch syndrome prevalence was 10% overall and 38.5% among MMR-D SBAs. Median age at SBA diagnosis was similar in non-Lynch syndrome MMR-D versus MMR-proficient (MMR-P) SBAs (65 vs. 61; P 1⁄4 0.75), but significantly younger in Lynch syndrome (47.5 vs. 61; P 1⁄4 0.03). The prevalence of synchronous/ metachronous cancers was 9% (6/67) in MMR-P versus 34.6% (9/ 26) in MMR-D SBA, with 66.7% (6/9) of these in Lynch syndrome (P 1⁄4 0.0002). In the MMR-P group, 52.2% (35/67) of patients presented with metastatic disease, compared with 23.1% (6/26) in the MMR-D group (P 1⁄4 0.008). In MMR-P stage I/II patients, 88.2% (15/17) recurred, compared with 18.2% (2/11) in the MMR-D group (P 1⁄4 0.0002). Conclusions: When compared with MMR-P SBA, MMR-D SBA was associated with earlier stage disease and lower recurrence rates, similar to observations in colorectal cancer. With a 38.5% prevalence in MMR-D SBA, germline Lynch syndrome testing in MMR-D SBA is warranted. © 2020 American Association for Cancer Research.
Journal Title: Clinical Cancer Research
Volume: 27
Issue: 5
ISSN: 1078-0432
Publisher: American Association for Cancer Research  
Date Published: 2021-03-01
Start Page: 1429
End Page: 1437
Language: English
DOI: 10.1158/1078-0432.Ccr-20-2892
PROVIDER: scopus
PMCID: PMC7925361
PUBMED: 33199489
DOI/URL:
Notes: Article -- Export Date: 1 April 2021 -- Source: Scopus
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MSK Authors
  1. Kenneth Offit
    661 Offit
  2. Leonard B Saltz
    702 Saltz
  3. Philip B Paty
    409 Paty
  4. Arnold J Markowitz
    118 Markowitz
  5. Neil Howard Segal
    156 Segal
  6. Zsofia Kinga Stadler
    245 Stadler
  7. Diane Lauren Reidy
    224 Reidy
  8. Jinru Shia
    580 Shia
  9. Martin R Weiser
    403 Weiser
  10. Rona Denit Yaeger
    157 Yaeger
  11. Ahmet Zehir
    268 Zehir
  12. Garrett Nash
    177 Nash
  13. Michael Forman Berger
    558 Berger
  14. David P Kelsen
    470 Kelsen
  15. Nancy Kemeny
    470 Kemeny
  16. Jaclyn Frances Hechtman
    189 Hechtman
  17. Karuna   Ganesh
    33 Ganesh
  18. Louise Catherine Connell
    24 Connell
  19. Kaitlyn Ann Tkachuk
    13 Tkachuk
  20. Zalak Patel
    8 Patel
  21. Rania A Sheikh
    4 Sheikh