Li Jing-Ping, Zhang Xiang-Mei, Zhang Zhenzhen, Zheng Li-Hua, Jindal Sonali, Liu Yun-Jiang
Department of Breast Surgery, the Fourth Hospital of Hebei Medical University.
Research Center, the Fourth Hospital of Hebei Medical University.
Medicine (Baltimore). 2019 May;98(18):e15449. doi: 10.1097/MD.0000000000015449.
TP53 gene is mutated in approximately 80% of triple-negative breast cancer (TNBC). However, the prognostic significance of immunohistochemical (IHC)-detected p53 protein expression remains controversial in TNBC. In this study, we retrospectively analyzed the association between IHC-detected p53 expression and the prognosis in a cohort of 278 patients with stage I-III triple-negative breast invasive ductal carcinoma (IDC), who received surgery at the department of breast surgery in the Fourth Hospital of Hebei Medical University from 2010-01 to 2012-12. We found a positive expression ratio of IHC-detected p53 in triple-negative breast IDC of 58.6% (163/278). Furthermore, levels of expression were significantly associated with vessel tumor emboli and higher histologic grade (P = .038, P = .043, respectively), with the highest expression level observed in G3 breast cancer (64.7%). Additionally, Kaplan-Meier analysis showed that p53 expression indicated worse overall survival (OS) in the whole cohort (79.6% vs 89.6%, Log-rank test P = .025) as well as in stratified prognostic stage II patients (90.8% vs 100%, Log-rank test P = .027). The mortality risk of p53 expression patients was 2.22 times higher than that of p53 negative patients (HR: 2.222; 95%CI: 1.147-4.308). In addition, p53 expression was also associated with poor disease-free survival (DFS) (76.7% vs 86.8%, P = .020). Cox proportional hazard ratio model showed p53 expression was an independent risk factor for OS (P = .018) and DFS (P = .018) after controlling for tumor size, lymph node status, and vessel tumor emboli. Altogether, our data showed that IHC-detected p53 expression is a promising prognostic candidate for poor survival in triple-negative breast IDC patients. However, more studies are needed to determine if p53 may be applied to clinical practice as a biomarker and/or novel therapeutic target for TNBC.
在大约80%的三阴性乳腺癌（TNBC）中，TP53基因发生突变。然而，免疫组织化学（IHC）检测到的p53蛋白表达的预后意义在TNBC中仍存在争议。在本研究中，我们回顾性分析了2010年1月至2012年12月在河北医科大学第四医院乳腺外科接受手术的278例I-III期三阴性乳腺浸润性导管癌（IDC）患者中，IHC检测到的p53表达与预后之间的关联。我们发现三阴性乳腺IDC中IHC检测到的p53阳性表达率为58.6%（163/278）。此外，表达水平与血管肿瘤栓子和更高的组织学分级显著相关（分别为P = 0.038，P = 0.043），在G3级乳腺癌中观察到最高表达水平（64.7%）。此外，Kaplan-Meier分析显示，p53表达表明整个队列的总生存期（OS）较差（79.6%对89.6%，对数秩检验P = 0.025）以及分层预后II期患者（90.8%对100%，对数秩检验P = 0.027）。p53表达患者的死亡风险比p53阴性患者高2.22倍（HR：2.222；95%CI：1.147 - 4.308）。此外，p53表达也与无病生存期（DFS）差相关（76.7%对86.8%，P = 0.020）。Cox比例风险模型显示，在控制肿瘤大小、淋巴结状态和血管肿瘤栓子后，p53表达是OS（P = 0.018）和DFS（P = 0.018）的独立危险因素。总之，我们的数据表明，IHC检测到的p53表达是三阴性乳腺IDC患者生存不良的一个有前景的预后指标。然而，需要更多的研究来确定p53是否可以作为TNBC的生物标志物和/或新的治疗靶点应用于临床实践。
