Clinicopathological significance of loss of ARID1A immunoreactivity in ovarian clear cell carcinoma

Daichi Maeda, Tsui Lien Mao, Masashi Fukayama, Shunsuke Nakagawa, Tetsu Yano, Yuji Taketani, Ie Ming Shih

Research output: Contribution to journalArticle

Abstract

Recent genome-wide analysis has demonstrated that somatic mutations in ARID1A (BAF250) are the most common molecular genetic changes in ovarian clear cell carcinoma (OCCC). ARID1A mutations, which occur in approximately half of OCCC cases, lead to deletion of the encoded protein and inactivation of the putative tumor suppressor. In this study, we determined the significance of loss of ARID1A immunoreactivity with respect to several clinicopathological features in a total of 149 OCCCs. First, we demonstrated that ARID1A immunohistochemistry showed concordance with the mutational status in 91% of cases with 100% sensitivity and 66% specificity. Specifically, among 12 OCCC cases for which ARIDA mutational status was known, ARIDIA immunoreactivity was undetectable in all 9 cases harboring ARID1A mutations and was undetectable in one of 3 cases with wild-type ARID1A. With respect to the entire cohort, ARID1A immunoreactivity was undetectable in 88 (59%) of 149 OCCCs. There was no significant difference between ARID1A negative and positive cases in terms of histopathologic features, age, clinical stage, or overall survival. In conclusion, this study provides further evidence that mutations in ARID1A resulted in loss of ARID1A protein expression in OCCC, although no significant differences between ARID1A positive and negative cases were observed with respect to any clinicopathological features examined.

Original languageEnglish (US)
Pages (from-to)5120-5128
Number of pages9
JournalInternational Journal of Molecular Sciences
Volume11
Issue number12
DOIs
StatePublished - Dec 2010

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mutations
cancer
Cells
Proteins
Carcinoma
Mutation
Tumors
Genes
proteins
suppressors
deletion
genome
deactivation
Molecular Biology
tumors
Immunohistochemistry
Genome
Sensitivity and Specificity
sensitivity
Neoplasms

Keywords

  • ARID1A
  • Ovarian
  • Pathology

ASJC Scopus subject areas

  • Computer Science Applications
  • Molecular Biology
  • Catalysis
  • Inorganic Chemistry
  • Spectroscopy
  • Organic Chemistry
  • Physical and Theoretical Chemistry
  • Medicine(all)

Cite this

Clinicopathological significance of loss of ARID1A immunoreactivity in ovarian clear cell carcinoma. / Maeda, Daichi; Mao, Tsui Lien; Fukayama, Masashi; Nakagawa, Shunsuke; Yano, Tetsu; Taketani, Yuji; Shih, Ie Ming.

In: International Journal of Molecular Sciences, Vol. 11, No. 12, 12.2010, p. 5120-5128.

Research output: Contribution to journalArticle

Maeda, Daichi ; Mao, Tsui Lien ; Fukayama, Masashi ; Nakagawa, Shunsuke ; Yano, Tetsu ; Taketani, Yuji ; Shih, Ie Ming. / Clinicopathological significance of loss of ARID1A immunoreactivity in ovarian clear cell carcinoma. In: International Journal of Molecular Sciences. 2010 ; Vol. 11, No. 12. pp. 5120-5128.
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abstract = "Recent genome-wide analysis has demonstrated that somatic mutations in ARID1A (BAF250) are the most common molecular genetic changes in ovarian clear cell carcinoma (OCCC). ARID1A mutations, which occur in approximately half of OCCC cases, lead to deletion of the encoded protein and inactivation of the putative tumor suppressor. In this study, we determined the significance of loss of ARID1A immunoreactivity with respect to several clinicopathological features in a total of 149 OCCCs. First, we demonstrated that ARID1A immunohistochemistry showed concordance with the mutational status in 91{\%} of cases with 100{\%} sensitivity and 66{\%} specificity. Specifically, among 12 OCCC cases for which ARIDA mutational status was known, ARIDIA immunoreactivity was undetectable in all 9 cases harboring ARID1A mutations and was undetectable in one of 3 cases with wild-type ARID1A. With respect to the entire cohort, ARID1A immunoreactivity was undetectable in 88 (59{\%}) of 149 OCCCs. There was no significant difference between ARID1A negative and positive cases in terms of histopathologic features, age, clinical stage, or overall survival. In conclusion, this study provides further evidence that mutations in ARID1A resulted in loss of ARID1A protein expression in OCCC, although no significant differences between ARID1A positive and negative cases were observed with respect to any clinicopathological features examined.",
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