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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