Details

Autor(en) / Beteiligte

• Latham, Alicia
• Shia, Jinru
• Patel, Zalak
• Reidy-Lagunes, Diane L
• Segal, Neil H
• Yaeger, Rona
• Ganesh, Karuna
• Connell, Louise
• Kemeny, Nancy E
• Kelsen, David P
• Hechtman, Jaclyn F
• Nash, Garrett M
• Paty, Philip B
• Zehir, Ahmet
• Tkachuk, Kaitlin A
• Sheikh, Rania
• Markowitz, Arnold J
• Mandelker, Diana
• Offit, Kenneth
• Berger, Michael F
• Cercek, Andrea
• Garcia-Aguilar, Julio
• Saltz, Leonard B
• Weiser, Martin R
• Stadler, Zsofia K

Titel

Characterization and Clinical Outcomes of DNA Mismatch Repair-deficient Small Bowel Adenocarcinoma

Ist Teil von

• Clinical cancer research, 2021-03, Vol.27 (5), p.1429-1437

Ort / Verlag

United States

Erscheinungsjahr

2021

Quelle

MEDLINE

Beschreibungen/Notizen

• 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. 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 ( , and ). Clinical variables were correlated with MMR/MSI status. 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; = 0.75), but significantly younger in Lynch syndrome (47.5 vs. 61; = 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 ( = 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 ( = 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 ( = 0.0002). 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.