title: ARID1A immunohistochemistry improves outcome prediction in invasive urothelial carcinoma of urinary bladder.
abstract: AT-rich interactive domain 1A (ARID1A) is tumor suppressor gene that interacts with BRG1 adenosine triphosphatase to form a SWI/SNF chromatin remodeling protein complex. Inactivation of ARID1A has been described in several neoplasms, including epithelial ovarian and endometrial carcinomas, and has been correlated with prognosis. In the current study, ARID1A expression in urothelial carcinoma (UC) of the bladder and its association with clinicopathological parameters and outcome are addressed. Five tissue microarrays were constructed from 136 cystectomy specimens performed for UC at our institution. Nuclear ARID1A staining was evaluated using immunohistochemistry. An H-score was calculated as the sum of the products of intensity (0-3) multiplied by extent of expression (0%-100%). Average H-score per case was used for statistical analysis. ARID1A expression was categorized in low and high using Youden index to define the cut point. ARID1A expression significantly increased from normal to noninvasive UC to invasive UC. For both tumor progression and cancer death, Youden index yielded an H-score of 288 as the optimal cut point for ARID1A expression. Low ARID1A expression showed a tendency for lower risk of tumor progression and cancer mortality. Adding ARID1A expression to pathologic features offers a better model for predicting outcome than pathologic features alone. Low ARID1A expression was more frequently seen in earlier stage disease. There was a tendency for low ARID1A expression to predict better outcome. More importantly, the findings indicate that adding ARID1A expression to pathologic features increases the goodness of fit of the predictive model.
authors.affiliation: Department of Pathology, Johns Hopkins University, Baltimore 21231, MD.
authors.forename: Sheila F
authors.initials: SF
authors.lastname: Faraj
authors.affiliation: Department of Pathology, Johns Hopkins University, Baltimore 21231, MD; Norte University School of Medicine, Asunción 1614, Paraguay.
authors.forename: Alcides
authors.initials: A
authors.lastname: Chaux
authors.affiliation: Department of Pathology, Johns Hopkins University, Baltimore 21231, MD.
authors.forename: Nilda
authors.initials: N
authors.lastname: Gonzalez-Roibon
authors.affiliation: Department of Pathology, Johns Hopkins University, Baltimore 21231, MD.
authors.forename: Enrico
authors.initials: E
authors.lastname: Munari
authors.affiliation: Department of Pathology, Johns Hopkins University, Baltimore 21231, MD.
authors.forename: Carla
authors.initials: C
authors.lastname: Ellis
authors.affiliation: Department of Oncology, Johns Hopkins University, Baltimore 21231, MD.
authors.forename: Tina
authors.initials: T
authors.lastname: Driscoll
authors.affiliation: Department of Oncology, Johns Hopkins University, Baltimore 21231, MD.
authors.forename: Mark P
authors.initials: MP
authors.lastname: Schoenberg
authors.affiliation: Department of Oncology, Johns Hopkins University, Baltimore 21231, MD.
authors.forename: Trinity J
authors.initials: TJ
authors.lastname: Bivalacqua
authors.affiliation: Department of Pathology, Johns Hopkins University, Baltimore 21231, MD; Department of Urology, Johns Hopkins University, Baltimore 21231, MD; Department of Gynecologic Pathology Division, Johns Hopkins University, Baltimore 21231, MD.
authors.forename: Ie-Ming
authors.initials: IeM
authors.lastname: Shih
authors.affiliation: Department of Pathology, Johns Hopkins University, Baltimore 21231, MD; Department of Oncology, Johns Hopkins University, Baltimore 21231, MD; Department of Urology, Johns Hopkins University, Baltimore 21231, MD. Electronic address: gnetto1@jhmi.edu.
authors.forename: George J
authors.initials: GJ
authors.lastname: Netto
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D002295:Carcinoma, Transitional Cell / Q000378:metabolism / Q000473:pathology* / Q000601:surgery; D015653:Cystectomy; D004268:DNA-Binding Proteins; D018450:Disease Progression; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D008297:Male; D008875:Middle Aged; D009687:Nuclear Proteins / Q000378:metabolism*; D011379:Prognosis; D014157:Transcription Factors / Q000378:metabolism*; D016896:Treatment Outcome; D001749:Urinary Bladder Neoplasms / Q000378:metabolism / Q000473:pathology* / Q000601:surgery; D019459:Urothelium / Q000378:metabolism / Q000473:pathology* / Q000601:surgery
chemical_list: C112476:ARID1A protein, human; D004268:DNA-Binding Proteins; D009687:Nuclear Proteins; D014157:Transcription Factors
keywords: ARID1A; BAF250A; Bladder cancer; NMI-BC; Prognosis