Center for Prostate Disease Research, Murtha Cancer Center Research Program, Department of Surgery, Uniformed Services University of the Health Sciences, Bethesda, MD, 20817, USA.
Henry M. Jackson Foundation for the Advancement of Military Medicine, Inc., Bethesda, MD, 20817, USA.
Sci Rep. 2022 Mar 30;12(1):5404. doi: 10.1038/s41598-022-08826-5.
TP53 is one of the most frequently altered genes in prostate cancer. The precise assessment of its focal alterations in primary tumors by immunohistochemistry (IHC) has significantly enhanced its prognosis. p53 protein expression and lymphovascular invasion (LVI) were evaluated for predicting metastatic progression by IHC staining of representative whole-mounted prostate sections from a cohort of 189 radical prostatectomy patients with up to 20 years of clinical follow-up. Kaplan-Meier survival curves were used to examine time to distant metastasis (DM) as a function of p53 expression and LVI status. TP53 targeted sequencing was performed in ten tumors with the highest expression of p53 staining. Nearly half (49.8%) of prostate tumors examined showed focal p53 expression while 26.6% showed evidence of LVI. p53(+) tumors had higher pathologic T stage, Grade Group, Nuclear Grade, and more frequent LVI. p53 expression of > 5% and LVI, individually and jointly, are associated with poorer DM-free survival. TP53 mutations were detected in seven of ten tumors sequenced. Four tumors with the highest p53 expression harbored likely pathogenic or pathogenic mutations. High levels of p53 expression suggest the likelihood of pathogenic TP53 alterations and, together with LVI status, could enhance early prognostication of prostate cancer progression.
TP53 是前列腺癌中最常发生改变的基因之一。通过免疫组织化学（IHC）对原发性肿瘤中其局灶性改变的精确评估显著增强了其预后判断。通过对 189 例接受根治性前列腺切除术的患者的代表性全前列腺切片进行 IHC 染色，评估了 p53 蛋白表达和淋巴血管侵犯（LVI）在预测转移进展方面的作用，这些患者的临床随访时间长达 20 年。通过 Kaplan-Meier 生存曲线，研究了 p53 表达和 LVI 状态与远处转移（DM）时间的关系。对 10 例 p53 染色表达最高的肿瘤进行了 TP53 靶向测序。在检查的前列腺肿瘤中，近一半（49.8%）表现出局灶性 p53 表达，而 26.6%显示出 LVI 的证据。p53(+)肿瘤具有更高的病理 T 分期、分级组、核分级和更频繁的 LVI。p53 表达>5%和 LVI 单独或联合与较差的无 DM 生存相关。在测序的 10 个肿瘤中检测到了 7 个 TP53 突变。在表达 p53 最高的 4 个肿瘤中，存在可能的致病性或致病性突变。高水平的 p53 表达提示存在致病性 TP53 改变的可能性，并且与 LVI 状态一起，可以增强对前列腺癌进展的早期预后判断。
