Open AccessIncreased centrosome number in BRCA ‐related breast cancer specimens determined by immunofluorescence analysis
Author(s) -
Watanabe Gou,
Chiba Natsuko,
Nomizu Tadashi,
Furuta Akihiko,
Sato Kaolu,
Miyashita Minoru,
Tada Hiroshi,
Suzuki Akihiko,
Ohuchi Noriaki,
Ishida Takanori
Publication year - 2018
Publication title -
cancer science
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.035
H-Index - 141
eISSN - 1349-7006
pISSN - 1347-9032
DOI - 10.1111/cas.13595
Subject(s) - centrosome , breast cancer , immunofluorescence , medicine , oncology , cancer , confidence interval , area under the curve , cancer research , pathology , biology , antibody , immunology , cell cycle
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. As 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 using immunofluorescence of γ‐tubulin (a marker of centrosome) foci. The number of foci per cell was higher in cases with BRCA mutation compared to wild‐type cases, that is, 1.9 (95% confidence interval [CI], 1.5‐2.3) vs 0.5 (95% CI, 0.2‐0.8) ( P < .001). Specifically, foci numbers per cell in BRCA1 and BRCA2 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 = .042 and P < .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.