Translational Cancer Genetics Team, The Institute of Cancer Research, Surrey, UK.
Oncol Rep. 2010 Feb;23(2):299-305.
Prostate cancers in men with germline BRCA1 and BRCA2 mutations are more aggressive than morphologically similar cancers in men without these mutations. This study was performed to test the hypothesis that enhanced expression of Ki-67, as a surrogate of cell proliferation, is a characteristic feature of prostate cancers occurring in BRCA1 or BRCA2 mutation carriers. The study cohort comprised 20 cases of prostate cancer in mutation carriers and 126 control sporadic prostate cancers. Of the combined sample cohort, 65.7% stained only within malignant tissues while 0.7% stained in both malignant and benign tissues (p<0.001). Significantly increased expression of Ki-67 occurred in prostate cancers with higher Gleason score (p<0.001). Elevated Ki-67 expression was identified in 71% of prostate cancers in BRCA1 or BRCA2 mutation carriers and in 67% of the sporadic controls (p>0.5). Similar results were obtained when the data were analysed using a threshold set at 3.5 and 7.1%. This study shows that elevated expression of Ki-67 is associated both with aggressive prostate cancers and with high Gleason score irrespective of whether their occurrence is against a background of BRCA1 or BRCA2 mutations or as sporadic disease. The data suggest that, since elevated Ki-67 does not distinguish prostate cancers occurring in BRCA1 or BRCA2 mutation carriers from sporadic prostatic malignancies, the effects of these genetic mutations are probably independent. While all prostate cancers occurring in the presence of BRCA germline mutations are clinically aggressive, their potentially different phenotypes consistently involve maximal rates of cell proliferation.
携带种系 BRCA1 和 BRCA2 突变的男性的前列腺癌比没有这些突变的男性的形态相似的前列腺癌更具侵袭性。本研究旨在验证以下假设，即作为细胞增殖的替代物的 Ki-67 增强表达是 BRCA1 或 BRCA2 突变携带者中发生的前列腺癌的特征特征。该研究队列包括 20 例突变携带者中的前列腺癌和 126 例对照散发性前列腺癌。在联合样本队列中，65.7％的病例仅在恶性组织中染色，而 0.7％的病例在恶性和良性组织中均染色（p<0.001）。Ki-67 的表达明显增加发生在具有较高 Gleason 评分的前列腺癌中（p<0.001）。BRCA1 或 BRCA2 突变携带者中的 71％的前列腺癌和散发性对照组中的 67％的前列腺癌中存在 Ki-67 表达升高（p>0.5）。当使用 3.5 和 7.1％的阈值分析数据时，得到了相似的结果。本研究表明，Ki-67 的高表达与侵袭性前列腺癌和高 Gleason 评分均相关，而不论其发生是否伴有 BRCA1 或 BRCA2 突变或散发性疾病。数据表明，由于升高的 Ki-67 不能区分 BRCA1 或 BRCA2 突变携带者中发生的前列腺癌与散发性前列腺恶性肿瘤，因此这些遗传突变的作用可能是独立的。尽管存在 BRCA 种系突变的所有前列腺癌均具有临床侵袭性，但它们潜在的不同表型始终涉及最大的细胞增殖率。
