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

Maeda D, Mao TL, Fukayama M, Nakagawa S, Yano T, Taketani Y, Shih IeM - Int J Mol Sci (2010)

Bottom Line: 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.

View Article: PubMed Central - PubMed

Affiliation: Department of Pathology, Graduate School of Medicine, the University of Tokyo, Tokyo, Japan; E-Mails: daichimaeda@gmail.com (D.M.); mfukayama-tky@umin.net (M.F.).

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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Related in: MedlinePlus

ARID immunoreactivity in three representative OCCCs which differ with respect to ARID1A mutational status. The OCCC with wild-type ARID1A shows intense and diffuse nuclear immunoreactivity in both tumor and stromal cells. In contrast, the other two cases, both with insertion mutations, exhibit undetectable ARID1A immunoreactivity while the stromal cells are positive, serving as internal positive controls.
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f1-ijms-11-05120: ARID immunoreactivity in three representative OCCCs which differ with respect to ARID1A mutational status. The OCCC with wild-type ARID1A shows intense and diffuse nuclear immunoreactivity in both tumor and stromal cells. In contrast, the other two cases, both with insertion mutations, exhibit undetectable ARID1A immunoreactivity while the stromal cells are positive, serving as internal positive controls.

Mentions: We employed immunohistochemistry to evaluate the expression of ARID1A in OCCC tissues. Results of ARID1A immunohistochemistry in OCCCs are summarized in Table 1. ARID1A immunoreactivity was detected exclusively in nuclei of cells, and when protein expression was observed, it was always seen in a diffuse pattern. Positive immunoreactivity of ARID1A was recorded in 61 (41%) of 149 cases. Specifically, 88 (59%), 36 (24%), and 25 (17%) of 149 cases had a staining intensity score of 0, 1+, and 2+, respectively. Histological features in representative cases with different ARID1A immunostaining intensities and their mutational status are shown in Figure 1. Intra-tumoral non-neoplastic mesenchymal cells were usually strongly positive for ARID1A, and they served as positive controls, especially for negative cases.


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

Maeda D, Mao TL, Fukayama M, Nakagawa S, Yano T, Taketani Y, Shih IeM - Int J Mol Sci (2010)

ARID immunoreactivity in three representative OCCCs which differ with respect to ARID1A mutational status. The OCCC with wild-type ARID1A shows intense and diffuse nuclear immunoreactivity in both tumor and stromal cells. In contrast, the other two cases, both with insertion mutations, exhibit undetectable ARID1A immunoreactivity while the stromal cells are positive, serving as internal positive controls.
© Copyright Policy - open-access
Related In: Results  -  Collection

License 1 - License 2
Show All Figures
getmorefigures.php?uid=PMC3100854&req=5

f1-ijms-11-05120: ARID immunoreactivity in three representative OCCCs which differ with respect to ARID1A mutational status. The OCCC with wild-type ARID1A shows intense and diffuse nuclear immunoreactivity in both tumor and stromal cells. In contrast, the other two cases, both with insertion mutations, exhibit undetectable ARID1A immunoreactivity while the stromal cells are positive, serving as internal positive controls.
Mentions: We employed immunohistochemistry to evaluate the expression of ARID1A in OCCC tissues. Results of ARID1A immunohistochemistry in OCCCs are summarized in Table 1. ARID1A immunoreactivity was detected exclusively in nuclei of cells, and when protein expression was observed, it was always seen in a diffuse pattern. Positive immunoreactivity of ARID1A was recorded in 61 (41%) of 149 cases. Specifically, 88 (59%), 36 (24%), and 25 (17%) of 149 cases had a staining intensity score of 0, 1+, and 2+, respectively. Histological features in representative cases with different ARID1A immunostaining intensities and their mutational status are shown in Figure 1. Intra-tumoral non-neoplastic mesenchymal cells were usually strongly positive for ARID1A, and they served as positive controls, especially for negative cases.

Bottom Line: 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.

View Article: PubMed Central - PubMed

Affiliation: Department of Pathology, Graduate School of Medicine, the University of Tokyo, Tokyo, Japan; E-Mails: daichimaeda@gmail.com (D.M.); mfukayama-tky@umin.net (M.F.).

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.

Show MeSH
Related in: MedlinePlus