title: ARID1A alteration in aggressive urothelial carcinoma and variants of urothelial carcinoma.
abstract: ARID1A mutation leads to loss of the products of this tumor-suppressor gene. Studies demonstrated ARID1A mutation in 20% of stage IV urothelial carcinomas (UCs) with worse prognosis. The expression of ARID1A in aggressive variants of UC is not studied properly. From 2000 to 2015, 81 variants of UC (29 micropapillary, 33 sarcomatoid, 31 small cell, 2 nested, and 3 plasmacytoid variants) were identified in the archives of Rhode Island Hospital. Immunohistochemistry for anti-ARID1A antibody (Sigma-Aldrich, St Louis, MO) was performed. The staining pattern was semiquantitatively scored, and results were analyzed by Fisher exact test (2 tailed) on contingency tables, survival curve, and log-rank test. Patients were predominantly male (78%) with mean age of 67.9 years. The plasmacytoid variant group occurred in younger ages (mean: 54 years). Half of the specimens contained concurrent conventional UCs. Normal urothelium invariably exhibited strong ARID1A nuclear staining. There was no difference in expression between upper and lower tracts. ARID1A expression was lower in the variants compared with conventional UCs (P<.0001). In micropapillary UCs, an inverse correlation between stage and ARID1A expression was noted, with significant correlation between ARID1A expression and overall survival (P=.0221). Sarcomatoid UCs and small cell CCs showed lower ARID1A expression compared with UCs that was not statistically significant, and neither showed any significant correlation with stage or overall survival. ARID1A expression is significantly decreased in higher stages of UC and its aggressive variants; therefore, ARID1A mutation appears to play an important role in the prognosis of UC and its aggressive variants. This finding may have therapeutic implications.
authors.affiliation: Department of Pathology and Laboratory Medicine, Warren Alpert Medical School of Brown University, Rhode Island Hospital, 593 Eddy St, Providence, RI 02903.
authors.forename: Jianhong
authors.initials: J
authors.lastname: Li
authors.affiliation: Department of Pathology and Laboratory Medicine, Warren Alpert Medical School of Brown University, Rhode Island Hospital, 593 Eddy St, Providence, RI 02903.
authors.forename: Shaolei
authors.initials: S
authors.lastname: Lu
authors.affiliation: Department of Pathology and Laboratory Medicine, Warren Alpert Medical School of Brown University, Rhode Island Hospital, 593 Eddy St, Providence, RI 02903.
authors.forename: Kara
authors.initials: K
authors.lastname: Lombardo
authors.affiliation: Department of Pathology and Laboratory Medicine, Warren Alpert Medical School of Brown University, Rhode Island Hospital, 593 Eddy St, Providence, RI 02903.
authors.forename: Rene
authors.initials: R
authors.lastname: Monahan
authors.affiliation: Department of Pathology and Laboratory Medicine, Warren Alpert Medical School of Brown University, Rhode Island Hospital, 593 Eddy St, Providence, RI 02903. Electronic address: aamin@lifespan.org.
authors.forename: Ali
authors.initials: A
authors.lastname: Amin
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D014408:Biomarkers, Tumor / Q000032:analysis* / Q000235:genetics; D002277:Carcinoma / Q000737:chemistry* / Q000235:genetics / Q000473:pathology / Q000628:therapy; D004268:DNA-Binding Proteins; D016208:Databases, Factual; D015536:Down-Regulation; D005260:Female; D020022:Genetic Predisposition to Disease; D006801:Humans; D007150:Immunohistochemistry; D007680:Kidney Neoplasms / Q000737:chemistry* / Q000235:genetics / Q000473:pathology / Q000628:therapy; D008297:Male; D008875:Middle Aged; D009154:Mutation; D009367:Neoplasm Staging; D009687:Nuclear Proteins / Q000032:analysis* / Q000235:genetics; D010641:Phenotype; D012189:Retrospective Studies; D012237:Rhode Island; D014157:Transcription Factors / Q000032:analysis* / Q000235:genetics; D016896:Treatment Outcome; D001749:Urinary Bladder Neoplasms / Q000737:chemistry* / Q000235:genetics / Q000473:pathology / Q000628:therapy; D019459:Urothelium / Q000737:chemistry* / Q000473:pathology
chemical_list: C112476:ARID1A protein, human; D014408:Biomarkers, Tumor; D004268:DNA-Binding Proteins; D009687:Nuclear Proteins; D014157:Transcription Factors
keywords: ARID1A; Micropapillary; Nested; Plasmacytoid; Sarcomatoid; Small cell; Urothelial carcinoma