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Immunocytochemistry for ARID1A as a potential biomarker in urine cytology of bladder cancer
- Source :
- Cancer cytopathologyReferences. 127(9)
- Publication Year :
- 2019
-
Abstract
- BACKGROUND Mutations of AT-rich interactive domain 1 (ARID1A) have been associated with a worse outcome after intravesical treatment with bacille Calmette-Guerin 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.
- Subjects :
- Male
Cancer Research
Pathology
medicine.medical_specialty
Urinary system
Immunocytochemistry
Urinary Bladder
030209 endocrinology & metabolism
03 medical and health sciences
0302 clinical medicine
Cytology
medicine
Biomarkers, Tumor
Humans
Urine cytology
Aged
Aged, 80 and over
Carcinoma, Transitional Cell
Bladder cancer
Tissue microarray
medicine.diagnostic_test
business.industry
High-Throughput Nucleotide Sequencing
Histology
Middle Aged
medicine.disease
Immunohistochemistry
DNA-Binding Proteins
Oncology
Urinary Bladder Neoplasms
Tissue Array Analysis
030220 oncology & carcinogenesis
Mutation
Female
business
Transcription Factors
Subjects
Details
- ISSN :
- 19346638
- Volume :
- 127
- Issue :
- 9
- Database :
- OpenAIRE
- Journal :
- Cancer cytopathologyReferences
- Accession number :
- edsair.doi.dedup.....6335e2ed409298d2b97658147bb0c19f