Department of Medicine, Memorial Sloan Kettering Cancer Center, New York, NY, USA.
Department of Epidemiology, Harvard T.H. Chan School of Public Health, Boston, MA, USA.
Carcinogenesis. 2020 Jul 14;41(7):904-908. doi: 10.1093/carcin/bgaa061.
DNA repair genes are commonly altered in metastatic prostate cancer, but BRCA1 mutations are rare. Preliminary studies suggest that higher tumor expression of the BRCA1 protein may be associated with worse prognosis. We undertook a prospective study among men with prostate cancer in the Health Professionals Follow-up Study and evaluated BRCA1 via immunohistochemical staining on tissue microarrays. BRCA1 was expressed in 60 of 589 tumors. Prevalence of BRCA1 positivity was 43% in the 14 men with metastases at diagnosis compared with 9% in non-metastatic tumors [difference, 33 percentage points; 95% confidence interval (CI), 7-59]. BRCA1-positive tumors had 2.16-fold higher Ki-67 proliferative indices (95% CI, 1.18-3.95), higher tumor aneuploidy as predicted from whole-transcriptome profiling, and higher Gleason scores. Among the 575 patients with non-metastatic disease at diagnosis, we evaluated the association between BRCA1 expression and development of lethal disease (metastasis or cancer-specific death, 69 events) during long-term follow-up (median, 18.3 years). A potential weak association of BRCA1 positivity with lethal disease (hazard ratio, 1.61; 95% CI, 0.82-3.15) was attenuated when adjusting for age, Gleason score and clinical stage (hazard ratio, 1.11; 95% CI, 0.54-2.29). In summary, BRCA1 protein expression is a feature of more proliferative and more aneuploid prostate tumors and is more common in metastatic disease. While not well suited as a prognostic biomarker in primary prostate cancer, BRCA1 protein expression may be most relevant in advanced disease.
DNA 修复基因在转移性前列腺癌中通常发生改变，但 BRCA1 突变很少见。初步研究表明，BRCA1 蛋白在肿瘤中的高表达可能与预后较差有关。我们在健康专业人员随访研究中对患有前列腺癌的男性进行了一项前瞻性研究，并通过组织微阵列的免疫组织化学染色评估了 BRCA1。BRCA1 在 589 个肿瘤中的 60 个中表达。在诊断时患有转移的 14 名男性中，BRCA1 阳性的患病率为 43%，而无转移肿瘤为 9%[差异，33 个百分点；95%置信区间（CI），7-59]。BRCA1 阳性肿瘤的 Ki-67 增殖指数高 2.16 倍（95%CI，1.18-3.95），根据全转录组谱预测的肿瘤非整倍体更高，Gleason 评分更高。在 575 名诊断时无转移疾病的患者中，我们评估了 BRCA1 表达与长期随访（中位随访时间为 18.3 年）期间致命疾病（转移或癌症特异性死亡，69 例事件）发展之间的关联。BRCA1 阳性与致命疾病的潜在弱关联（危险比，1.61；95%CI，0.82-3.15）在调整年龄、Gleason 评分和临床分期（危险比，1.11；95%CI，0.54-2.29）后减弱。总之，BRCA1 蛋白表达是更具增殖性和更多非整倍体前列腺肿瘤的特征，在转移性疾病中更为常见。虽然作为原发性前列腺癌的预后生物标志物不太合适，但 BRCA1 蛋白表达在晚期疾病中可能最为相关。
