Background: The majority of studies investigating the role of Ki67 labeling index (LI) in prostate carcinoma (PC) focused on localized PC treated radically, where Ki67 LI is regarded as a prognostic marker. The relevance of Ki67 in advanced PC remains largely unexplored. While Gleason score is still one of the best indicators of clinical outcomes in PC, differences in progression-free survival and overall survival in patients with high Gleason scores suggest that additional factors are involved in tumor progression. Understanding the underlying mechanisms could help to optimize treatment strategies for an individual patient. Here, we aimed to determine the inter- and intratumoral distribution of Ki67 LI in patients with PC with high Gleason scores and to correlate Ki67 LI with the status of ERG, PTEN, and Bcl-2. Methods: Immunohistochemistry for Ki67, ERG, PTEN, and Bcl-2 was performed on core needle biopsies from 112 patients with newly diagnosed PC Gleason score 8, 9, and 10. Results: Using a cutoff of ≥10%, 17/112 cases (15%) had a homogeneously low and 95/112 cases (85%) a high Ki67 LI. 41% of cases showed intratumoral heterogeneity containing areas with low and high proliferation. There was no association between Ki67 LI and ERG, PTEN, or Bcl-2 status. Conclusions: Our data demonstrate major inter- and intratumoral variability of Ki67 LI in high-grade PC with a surprisingly low Ki67 LI in a subset of cases. Further studies are necessary to explore the molecular basis and potential clinical implications of a paradoxically low proliferation rate in high-grade PC.
Pathobiology

中文翻译：

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Ki67 标记指数在 Gleason 评分高的新诊断前列腺癌中的高肿瘤间和肿瘤内变异性

背景：大多数调查 Ki67 标记指数 (LI) 在前列腺癌 (PC) 中的作用的研究都集中在根治性治疗的局部 PC 上，其中 Ki67 LI 被视为预后标志物。Ki67 在高级 PC 中的相关性在很大程度上仍未得到探索。虽然 Gleason 评分仍然是 PC 临床结果的最佳指标之一，但 Gleason 评分高的患者无进展生存期和总生存期的差异表明其他因素参与了肿瘤进展。了解潜在机制有助于优化个体患者的治疗策略。在这里，我们旨在确定 Ki67 LI 在 Gleason 评分高的 PC 患者中的肿瘤间和肿瘤内分布，并将 Ki67 LI 与 ERG、PTEN 和 Bcl-2 的状态相关联。方法：对 112 例新诊断 PC Gleason 评分 8、9 和 10 的患者的核心穿刺活检进行 Ki67、ERG、PTEN 和 Bcl-2 的免疫组织化学。结果：使用 ≥10% 的截止值，17/112 例(15%) Ki67 LI 均低，95/112 例 (85%) Ki67 LI 高。41% 的病例显示肿瘤内异质性包含低增殖和高增殖区域。Ki67 LI 与 ERG、PTEN 或 Bcl-2 状态之间没有关联。结论：我们的数据表明，高级别 PC 中 Ki67 LI 的主要肿瘤间和肿瘤内变异性在一部分病例中具有令人惊讶的低 Ki67 LI。需要进一步的研究来探索高级 PC 中自相矛盾的低增殖率的分子基础和潜在的临床意义。
病理学