Background: Next-generation sequencing has revealedTP53alterations in localized prostate cancer (PCa), suggesting growing clinical potential for p53 immunohistochemistry (IHC). Prior research supports the use of IHC for the detection of p53 overexpression to predict the presence ofTP53alterations known to be associated with adverse outcomes. However, to reach a consensus definition of p53 overexpression in PCa, further insights are needed. This study aimed to compare two fundamental approaches of evaluating p53 expression across a variety of specimens regarding PCa progression. Methods: This study included 84 patients (75% self-identified as African American) diagnosed with PCa between 1996 and 2021 at the DC VA Medical Center. Representative sections of core biopsies, radical prostatectomies, transurethral prostate resections, and metastatic deposits were examined. p53 nuclear expression was scored according to the highest intensity observed (0, 1+, 2+, 3+) and the percentage (0%, <1%, 1–5%, >5%) of tumor cells expressing any level of intensity in the aggregate tumor area. All slides were reviewed by two independent pathologists. Pertinent clinical data were collected. Results: A total of 34 patients (40%) exhibited p53 nuclear expression, of which 18 (21%) showed the maximum (3+) intensity. The presence of maximum intensity, regardless of percentage, was found to be associated with Grade Group (p< 0.001), higher PSA at biopsy (p< 0.001), BCR (p< 0.001) and metastasis (p< 0.001). Importantly, maximum p53 intensity was identified only in patients who developed metastatic disease. Conclusions: Maximum (3+) p53 nuclear intensity of any percentage is highly associated with disease progression in PCa, suggesting that optimal determination of p53 overexpression should incorporate intensity.
背景：新一代测序技术揭示了局限性前列腺癌（PCa）中的TP53基因改变，表明p53免疫组化（IHC）检测的临床潜力日益凸显。既往研究支持使用IHC检测p53过表达，以预测已知与不良预后相关的TP53基因改变。然而，要就前列腺癌中p53过表达达成共识性定义，仍需进一步深入研究。本研究旨在比较评估不同前列腺癌进展相关标本中p53表达的两种基本方法。 方法：本研究纳入了1996年至2021年间在华盛顿特区退伍军人事务医疗中心诊断为前列腺癌的84例患者（其中75%自认为非裔美国人）。对代表性穿刺活检、根治性前列腺切除术、经尿道前列腺切除术及转移灶切片进行了分析。根据观察到的最高核表达强度（0、1+、2+、3+）以及肿瘤区域内表达任何强度水平的肿瘤细胞百分比（0%、<1%、1–5%、>5%）对p53核表达进行评分。所有切片均由两名独立病理学家审阅。收集了相关临床数据。 结果：共有34例患者（40%）显示p53核表达，其中18例（21%）呈现最高（3+）强度。研究发现，无论表达百分比如何，最高强度p53表达的存在与以下因素显著相关：分级分组（p<0.001）、活检时较高PSA水平（p<0.001）、生化复发（p<0.001）及转移（p<0.001）。重要的是，最高强度p53表达仅出现在发生转移性疾病的患者中。 结论：任何百分比下的最高（3+）强度p53核表达与前列腺癌疾病进展高度相关，这表明p53过表达的最佳判定应纳入强度评估。
肿瘤(癌症)患者之家