Increased centrosome number in BRCA‐related breast cancer specimens determined by immunofluorescence analysis. Issue 6 (15th May 2018)

• Record Type: Journal Article
• Authors: Watanabe, Gou; Chiba, Natsuko; Nomizu, Tadashi; Furuta, Akihiko; Sato, Kaolu; Miyashita, Minoru; Tada, Hiroshi; Suzuki, Akihiko; Ohuchi, Noriaki; Ishida, Takanori
• Is Part Of: Cancer science. Volume 109:Issue 6(2018)
• Page Start: 2027
• Page End: 2035
• Publication Date: 2018-05-15
• Subjects: BRCA1 -- BRCA2 -- BRCA‐related breast cancer -- centrosome -- immunofluorescence; Cancer -- Periodicals; Neoplasms -- Periodicals; Research -- Periodicals; Electronic journals; 616.994005
• DOI: 10.1111/cas.13595
• Languages: English
• ISSNs: 1347-9032

Abstract

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. 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. Abstract : For predicting BRCA status by an immunostaining method, we focused the number of centrosome, because both of BRCA1 and 2 proteins control centrosome duplication. Our test was based on a quantitative analysis of centrosome numbers (γ‐tubulin foci) in cells in breast cancer tissue specimens. The number of foci per cell was higher in BRCA1 and/or 2 mutation as compared to wild‐type cases, i.e., 1.7 [95%; confidence interval (CI): 1.3‐2.2] vs 0.7 (95% CI: 0.4‐1.0) ( P < .001). The predictive value of our method for BRCA status (AUC = 0.86) was superior to that of existing pretests that are based on clinico‐pathological information, and had a sensitivity of 83%, specificity of 89%, and positive predictive value of 77%. We believe that this contribution is theoretically and practically relevant because, BRCA genetic tests have some problems, cost, privacy and counseling and cannot be routinely carried out in clinical practice; therefore, a more straightforward and broadly applicable test is needed.