{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,30]],"date-time":"2026-09-30T22:37:55Z","timestamp":1790807875809,"version":"4.1.0"},"reference-count":71,"publisher":"Wiley","issue":"21","license":[{"start":{"date-parts":[[2020,8,28]],"date-time":"2020-08-28T00:00:00Z","timestamp":1598572800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":["acsjournals.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Cancer"],"published-print":{"date-parts":[[2020,11]]},"abstract":"<jats:sec><jats:title>Background<\/jats:title><jats:p>The significance of DNA mismatch repair (MMR) deficiency in ampullary cancers (ACs) has not been established.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>In total, 127 ACs with invasive carcinomas measuring \u22653 mmthat had adequate tissue were analyzed immunohistochemically.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>MMR loss was detected in 18% of ACs (higher than in colorectal cancers). Twelve tumors with MLH1\u2010PMS2 loss were negative for <jats:italic>BRAF V600E<\/jats:italic> mutation, suggesting a Lynch syndrome association. MMR\u2010deficient tumors (n\u00a0=\u00a023), comparedwith MMR\u2010intact tumors (n\u00a0=\u00a0104), showed a striking male predominance (male:female ratio, 4.7). Although the deficient tumors had slightly larger invasion size (2.7 vs 2.1 cm), they also had more expansile growth and less invasiveness, including less perineural invasion, and they ultimately had lower tumor (T) classification and less lymph node metastasis (30% vs 53%; <jats:italic>P<\/jats:italic>\u00a0=\u00a0.04). More important, patients who had MMR\u2010deficient tumors had better clinical outcomes, with a 5\u2010year overall survival rate of 68% versus 45% (<jats:italic>P<\/jats:italic>\u00a0=\u00a0.03), which was even more pronounced in those who had higher Tclassification (5\u2010year overall survival, 69% vs 34%; <jats:italic>P<\/jats:italic>\u00a0=\u00a0.04). MMR deficiencyhad a statistically significant association with medullary phenotype, pushing\u2010border invasion, and tumor\u2010infiltrating immune cells, and it occurred more frequently in ampullary\u2010duodenal type tumors. Programed cell death\u2010ligand 1 (PD\u2010L1) levels analyzed in the 22 MMR\u2010deficient ACs revealed that all medullary carcinomas were positive. Nonmedullary MMR\u2010deficient carcinomas expressed PD\u2010L1 in 33% of tumors cells according to the criteria for a combined positive score \u22651, but all were negative according to the tumor proportion score\u22651 method.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusions<\/jats:title><jats:p>In ACs, MMR deficiency is even more frequent (18%) than in colon cancer and often has a Lynch\u2010suggestive profile, thus routine testing is warranted. Male gender, pushing\u2010border infiltration, ampullary\u2010duodenal origin, medullary histology, and tumor\u2010related inflammation have a significantly higher association with MMR deficiency. MMR\u2010deficient tumors have less aggressive behavior. PD\u2010L1 expression is common in medullary\u2010phenotype ACs, thus immunotherapy should be considered at least for this group.<\/jats:p><\/jats:sec>","DOI":"10.1002\/cncr.33135","type":"journal-article","created":{"date-parts":[[2020,8,28]],"date-time":"2020-08-28T17:00:33Z","timestamp":1598634033000},"page":"4788-4799","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":22,"title":["Frequency and clinicopathologic associations of DNA mismatch repair protein deficiency in ampullary carcinoma: Routine testing is indicated"],"prefix":"10.1002","volume":"126","author":[{"given":"Yue","family":"Xue","sequence":"first","affiliation":[{"name":"Department of Pathology Emory University Atlanta Georgia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7852-3851","authenticated-orcid":false,"given":"Serdar","family":"Balci","sequence":"additional","affiliation":[{"name":"Department of 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