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Immunocytochemistry for ARID1A as a potential biomarker in urine cytology of bladder cancer.

Abstract：

BACKGROUND:Mutations of AT-rich interactive domain 1 (ARID1A) have been associated with a worse outcome after intravesical treatment with bacille Calmette-Guérin in patients with non-muscle-invasive bladder cancer (NMIBC). Loss of ARID1A protein expression in urine cytology may serve as an indication of an ARID1A mutation. Therefore, the authors examined the expression of ARID1A in urine cytology and histological specimens of bladder cancer for correlation with ARID1A mutational status. METHODS:The authors constructed a tissue microarray containing samples from 164 tissue samples from 150 patients with NMIBC and 100 tissue samples from 81 patients with muscle-invasive bladder cancer. A second cohort consisted of archived cytological specimens and matched tissue sections from 62 patients with high-grade NMIBC. The authors established immunohistochemistry and immunocytochemistry (ICC) protocols, respectively, for the analysis of ARID1A protein expression in histological and cytological specimens. Confirmatory next-generation sequencing (NGS) was performed on tumor specimens using a targeted NGS panel containing all exonic regions of ARID1A. RESULTS:The prevalence of ARID1A loss of expression on the tissue microarray was 3.6% in NMIBC (6 of 164 tissue samples) and 10% in muscle-invasive bladder cancer (10 of 100 tissue samples) (P = .059). Loss of ARID1A expression in cytology was concordantly immunohistochemistry negative in 6 of 8 matched tissue specimens. NGS confirmed an ARID1A mutation on all 6 histology samples with loss of ARID1A expression. When NGS demonstrated an absence of ARID1A mutation, histology was concordantly positive (16 of 16 cases). CONCLUSIONS:The authors have suggest ARID1A ICC as a promising surrogate marker for ARID1A mutational status in patients with urothelial carcinoma. Pitfalls in ICC scoring include benign umbrella cells that often are negative for ARID1A. Further prospective studies are needed to determine the clinical relevance of ARID1A ICC in urinary cytology.

journal_name

Cancer Cytopathol

journal_title

Cancer cytopathology

authors

Dugas SG,Müller DC,Le Magnen C,Federer-Gsponer J,Seifert HH,Ruiz C,Savic Prince S,Vlajnic T,Zellweger T,Mertz KD,Bacon JVW,Wyatt AW,Rentsch CA,Bubendorf L

doi

10.1002/cncy.22167

subject

Has Abstract

pub_date

2019-09-01 00:00:00

pages

578-585

issue

eissn

1934-662X

issn

1934-6638

journal_volume

127

pub_type

杂志文章

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Immunocytochemistry for ARID1A as a potential biomarker in urine cytology of bladder cancer.