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

Gou Watanabe, Natsuko Chiba, Tadashi Nomizu, Akihiko Furuta, Kaolu Sato, Minoru Miyashita, Hiroshi Tada, Akihiko Suzuki, Noriaki Ohuchi, Takanori Ishida

Research output: Contribution to journalArticle

2 Citations (Scopus)

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.

Original languageEnglish
Pages (from-to)2027-2035
Number of pages9
JournalCancer science
Volume109
Issue number6
DOIs
Publication statusPublished - 2018 Jun

Keywords

  • BRCA-related breast cancer
  • BRCA1
  • BRCA2
  • centrosome
  • immunofluorescence

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

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