CONTEXT: - The clinicopathologic and prognostic significance of ARID1A mutation in esophageal adenocarcinoma (EAC) is unknown. OBJECTIVE: - To determine the morphological correlates and prognostic significance of ARID1A-deficient EAC. DESIGN: - One hundred twenty cases of primary EAC were evaluated for a predetermined set of histologic features and immunohistochemistry for ARID1A, p53, and MLH1 performed on EAC, as well as adjacent Barrett esophagus and Barrett esophagus-associated dysplasia, when feasible. Associations between categorical clinicopathologic variables were analyzed by Fisher exact test, and survival analysis was performed by a Cox proportional hazards analysis. RESULTS: - The study group included 97 men and 23 women (mean age, 66 years). Loss of ARID1A expression was seen in 12 of 120 EACs (10%). ARID1A-deficient tumors showed a strong correlation with a medullary and mucinous phenotype, and 8 of 12 (67%) had at least one feature reminiscent of high microsatellite instability colon carcinomas (mucinous or medullary differentiation, marked intratumoral or peritumoral lymphoid infiltrate). A mutant p53 pattern was present in 52 of 120 EACs (43%) and showed no correlation with ARID1A deficiency (P > .05). MLH1 loss was present in only 2 of 120 EACs (2%); both of which were also deficient in ARID1A. ARID1A-deficient EACs showed a trend toward increased risk of nodal metastasis but had no effect on overall patient survival. CONCLUSIONS: - ARID1A-deficient EACs show a phenotype similar to colon cancer with high microsatellite instability but do not appear to have any prognostic significance. Concurrent MLH1 loss is not seen in most ARID1A-deficient tumors, suggesting that ARID1A may be a primary driver of carcinogenesis in a subset of EACs.
CONTEXT: - The clinicopathologic and prognostic significance of ARID1A mutation in esophageal adenocarcinoma (EAC) is unknown. OBJECTIVE: - To determine the morphological correlates and prognostic significance of ARID1A-deficient EAC. DESIGN: - One hundred twenty cases of primary EAC were evaluated for a predetermined set of histologic features and immunohistochemistry for ARID1A, p53, and MLH1 performed on EAC, as well as adjacent Barrett esophagus and Barrett esophagus-associated dysplasia, when feasible. Associations between categorical clinicopathologic variables were analyzed by Fisher exact test, and survival analysis was performed by a Cox proportional hazards analysis. RESULTS: - The study group included 97 men and 23 women (mean age, 66 years). Loss of ARID1A expression was seen in 12 of 120 EACs (10%). ARID1A-deficient tumors showed a strong correlation with a medullary and mucinous phenotype, and 8 of 12 (67%) had at least one feature reminiscent of high microsatellite instability colon carcinomas (mucinous or medullary differentiation, marked intratumoral or peritumoral lymphoid infiltrate). A mutant p53 pattern was present in 52 of 120 EACs (43%) and showed no correlation with ARID1A deficiency (P > .05). MLH1 loss was present in only 2 of 120 EACs (2%); both of which were also deficient in ARID1A. ARID1A-deficient EACs showed a trend toward increased risk of nodal metastasis but had no effect on overall patient survival. CONCLUSIONS: - ARID1A-deficient EACs show a phenotype similar to colon cancer with high microsatellite instability but do not appear to have any prognostic significance. Concurrent MLH1 loss is not seen in most ARID1A-deficient tumors, suggesting that ARID1A may be a primary driver of carcinogenesis in a subset of EACs.
Authors: Karolin Heinze; Tayyebeh M Nazeran; Sandra Lee; Pauline Krämer; Evan S Cairns; Derek S Chiu; Samuel Cy Leung; Eun Young Kang; Nicola S Meagher; Catherine J Kennedy; Jessica Boros; Friedrich Kommoss; Hans-Walter Vollert; Florian Heitz; Andreas du Bois; Philipp Harter; Marcel Grube; Bernhard Kraemer; Annette Staebler; Felix Kf Kommoss; Sabine Heublein; Hans-Peter Sinn; Naveena Singh; Angela Laslavic; Esther Elishaev; Alex Olawaiye; Kirsten Moysich; Francesmary Modugno; Raghwa Sharma; Alison H Brand; Paul R Harnett; Anna DeFazio; Renée T Fortner; Jan Lubinski; Marcin Lener; Aleksandra Tołoczko-Grabarek; Cezary Cybulski; Helena Gronwald; Jacek Gronwald; Penny Coulson; Mona A El-Bahrawy; Michael E Jones; Minouk J Schoemaker; Anthony J Swerdlow; Kylie L Gorringe; Ian Campbell; Linda Cook; Simon A Gayther; Michael E Carney; Yurii B Shvetsov; Brenda Y Hernandez; Lynne R Wilkens; Marc T Goodman; Constantina Mateoiu; Anna Linder; Karin Sundfeldt; Linda E Kelemen; Aleksandra Gentry-Maharaj; Martin Widschwendter; Usha Menon; Kelly L Bolton; Jennifer Alsop; Mitul Shah; Mercedes Jimenez-Linan; Paul Dp Pharoah; James D Brenton; Kara L Cushing-Haugen; Holly R Harris; Jennifer A Doherty; Blake Gilks; Prafull Ghatage; David G Huntsman; Gregg S Nelson; Anna V Tinker; Cheng-Han Lee; Ellen L Goode; Brad H Nelson; Susan J Ramus; Stefan Kommoss; Aline Talhouk; Martin Köbel; Michael S Anglesio Journal: J Pathol Date: 2022-02-07 Impact factor: 9.883
Authors: Simon Schallenberg; Julian Bork; Ahlem Essakly; Hakan Alakus; Reinhard Buettner; Axel M Hillmer; Christiane Bruns; Wolfgang Schroeder; Thomas Zander; Heike Loeser; Florian Gebauer; Alexander Quaas Journal: BMC Cancer Date: 2020-01-06 Impact factor: 4.430