Division of Surgical Oncology, Tohoku University Graduate School of Medicine, Sendai, Japan.
Department of Cancer Biology, Institute of Development, Aging and Cancer, Tohoku University, Sendai, Japan.
Cancer Sci. 2018 Jun;109(6):2027-2035. doi: 10.1111/cas.13595. Epub 2018 May 15.
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.
BRCA 相关性乳腺癌可以通过预防性手术和强化随访方案来预防。然而，BRCA 基因检测不能常规进行，并且某些 BRCA 突变不能被定义为有害突变或正常变异。因此，易于进行 BRCA 的功能检测将有助于评估 BRCA 状态。据报道，BRCA 在调节中心体数量方面起作用，因此我们专注于癌症组织中的中心体数量。在这里，使用γ-微管蛋白（中心体的标志物）焦点的免疫荧光分析了 70 个具有已知 BRCA 状态的乳腺癌标本。与野生型病例相比，BRCA 突变病例的每个细胞焦点数更高，即 1.9（95%置信区间 [CI]，1.5-2.3）比 0.5（95%CI，0.2-0.8）（P<.001）。具体而言，BRCA1 和 BRCA2 突变病例中每个细胞的焦点数分别为 1.2（95%CI，0.6-1.8）和 2.2（95%CI，1.7-2.6），均高于野生型病例（P=0.042 和 P<.0001）。通过曲线下面积（AUC=0.86）确定的 γ-微管蛋白焦点作为 BRCA 状态的预测值优于 BRCAPRO（AUC=0.69）、Myriad Table（AUC=0.61）和 KOHBRA BRCA 风险计算器（AUC=0.65）预测试值。使用 γ-微管蛋白焦点预测 BRCA 状态的敏感性为 83%（19/23），特异性为 89%（42/47），阳性预测值为 77%（20/26）。因此，BRCA 的功能评估 γ-微管蛋白免疫荧光可以作为 BRCA 状态的新前瞻性检测方法。
