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Increased centrosome number in BRCA-related breast cancer specimens determined by immunofluorescence analysis.

Increased centrosome number in BRCA-related breast cancer specimens determined by immunofluorescence analysis.
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Watanabe G, Chiba N, Nomizu T, Furuta A, Sato K, Miyashita M, Tada H, Suzuki A, Ohuchi N, Ishida T,


Watanabe G, Chiba N, Nomizu T, Furuta A, Sato K, Miyashita M, Tada H, Suzuki A, Ohuchi N, Ishida T, (click to view)

Watanabe G, Chiba N, Nomizu T, Furuta A, Sato K, Miyashita M, Tada H, Suzuki A, Ohuchi N, Ishida T,

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Cancer science 2018 03 30() doi 10.1111/cas.13595

Abstract

BRCA-related breast carcinoma can be prevented through prophylactic surgery and an intensive follow-up regimen. However, BRCA genetic tests cannot be routinely performed, and some BRCA mutations could not be defined as deleterious mutations or normal variants. Therefore, an easy functional assay of BRCA will be useful to evaluate BRCA status. Since it has been reported that BRCA functions in the regulation of centrosome number, we focused on centrosome number in cancer tissues. Here, 70 breast cancer specimens with known BRCA status were analyzed via immunofluorescence of γ-tubulin (a marker of centrosome) foci. The number of foci per cell was higher in cases with BRCA mutation as compared to wild-type cases, i.e., 1.9 [95% confidence interval (CI): 1.5-2.3] vs. 0.5 (95% CI: 0.2-0.8) (P < 0.001). Specifically, foci numbers per cell in BRCA1 and 2 mutation cases were 1.2 (95% CI: 0.6-1.8) and 2.2 (95% CI: 1.7-2.6), respectively, both higher than those in wild-type cases (P = 0.042 and < 0.0001, respectively). The predictive value of γ-tubulin foci as determined by area under the curve (AUC = 0.86) for BRCA status was superior to BRCAPRO (AUC = 0.69), Myriad Table (AUC = 0.61), and KOHBRA BRCA risk calculator (AUC = 0.65) pretest values. The use of γ-tubulin foci to predict BRCA status had sensitivity = 83% (19/23), specificity = 89% (42/47), and positive predictive value = 77% (20/26). Thus, γ-tubulin immunofluorescence, a functional assessment of BRCA, can be used as a new prospective test of BRCA status. This article is protected by copyright. All rights reserved.

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