摘要
目的 探讨三阴型乳腺癌(triple negative breast cancer, TNBC)患者泛素羧基末端水解酶L1(ubiquitin C-terminal hydrolase L1, UCH-L1)、突变型p53(mutant p53, mt p53)的相关性及其对患者临床病理特征和预后的影响。方法 选取2013年12月至2024年7月北京儿童医院顺义妇儿医院TNBC患者97例,采用免疫组化EnVision法检测患者癌组织UCH-L1和mt p53的表达水平,分析UCH-L1、mt p53表达水平与TNBC患者临床病理特征、双微体同源基因2(mouse double minute 2, MDM2)、Hsc70羧基末端相互作用蛋白(carboxy terminus of Hsc70-interacting protein, CHIP)、E-钙黏蛋白(E-cadherin)的相关性。通过电话随访及复诊信息,记录患者无进展生存期(progression free survival, PFS),采用Kaplan-Meier生存曲线分析UCH-L1和mt p53的相关性及其对TNBC患者预后的影响。结果 97例TNBC患者均为女性,年龄28~83岁,平均55.5岁;组织学分级为Ⅰ级0例、Ⅱ级20例、Ⅲ级77例;淋巴结转移37例、肺转移2例。患者癌组织UCH-L1阳性56例(57.7%)、mt p53阳性64例(66.0%);mt p53与UCH-L1共表达48例(49.5%)。与mt p53阴性患者相比,mt p53阳性患者癌组织的UCH-L1阳性率较高(75.0%比24.2%),差异有统计学意义(P<0.05)。与UCH-L1阴性患者相比,UCH-L1阳性患者组织学分级为Ⅲ级(87.5%比68.3%)、基底样亚型(75.0%比53.7%)、MDM2阳性(71.4%比46.3%)及E-cadherin低表达(48.2%比26.8%)的比例均更高,差异均有统计学意义(P<0.05)。与mt p53阴性患者相比,mt p53阳性患者组织学分级为Ⅲ级(90.6%比57.6%)、基底样亚型(73.4%比51.5%)、MDM2阳性(71.9%比39.4%)、CHIP阳性(84.4%比63.6%)及E-cadherin低表达(45.3%比24.2%)的比例均较高,差异均有统计学意义(P<0.05)。97例患者随访4~130个月,平均随访40个月,复发和死亡23例(23.7%)。Kaplan-Meier分析结果显示,UCH-L1和mt p53共表达与非共表达患者PFS的比较,差异无统计学意义(P > 0.05)。结论 mt p53阳性的TNBC患者,常同时呈现UCH-L1阳性表达。UCH-L1、mt p53阳性的TNBC患者易出现更高的组织学分级和基底样亚型,以及更差的细胞黏附性。UCH-L1可能通过调控MDM2的表达,影响mt p53的稳定性和功能,共同促进TNBC的发生与发展。
Objective To explore the correlation between ubiquitin C-terminal hydrolase L1(UCH-L1)and mutant p53(mt p53)in patients with triple negative breast cancer(TNBC),and its impact on clinical pathological features and prognosis of the patients.Methods A total of 97 patients with TNBC from Shunyi Maternal and Children's Hospital of Beijing Children's Hospital were selected from December 2013 to July 2024,and the expression levels of UCH-L1 and mt p53 in cancer tissues were detected by immunohistochemical EnVision method,and the correlation between expression levels of UCH-L1,mt p53 and the clinical pathological features of TNBC patients,mouse double minute 2(MDM2),carboxy terminus of Hsc70-interacting protein(CHIP),E-cadherin was analyzed.The progression-free survival(PFS)was recorded by telephone and revisit follow-ups.Kaplan-Meier survival curve was used to analyze the correlation between UCH-L1 and mt p53 and its influence on the prognosis of TNBC patients.Results The 97 patients with TNBC were all females,aged from 28 to 83 years,with an average age of 55.5 years.Histologically,there was zero case for grade I,20 cases for grade II,and 77 cases for grade III.There were 37 cases of lymph node metastasis and two cases of lung metastasis.56 cases(57.7%)were UCH-L1 positive,and 64 cases(66.0%)were mt p53 positive.There were 48 cases(49.5%)of co-expression of mt p53 and UCH-L1.Compared to patients with negative mt p53,patients with positive mt p53 had higher positive rate of UCH-L1(75.0%vs.24.2%),and the difference was statistically significant(P<0.05).Compared to patients with negative UCH-L1,patients with positive UCH-L1 showed higher proportions of histological grade III(87.5%vs.68.3%),basal-like subtype(75.0%vs.53.7%),MDM2 positive(71.4%vs.46.3%),and lower expressions of E-cadherin(48.2%vs.26.8%),with all differences being statistically significant(P<0.05).Compared to patients with negative mt p53,patients with positive mt p53 also exhibited higher proportions of histological grade III(90.6%vs.57.6%),basal-like subtype(73.4%vs.51.5%),MDM2 positive(71.9%vs.39.4%),CHIP positive(84.4%vs.63.6%),and lower expressions of E-cadherin(45.3%vs.24.2%),with all differences being statistically significant(P<0.05).97 patients were follow-up for 4 to 130 months,with an average follow-up of 40 months,during which there were 23(23.7%)cases of recurrence and death.Kaplan-Meier analysis showed that there was no significant difference in PFS between patients expressing both UCH-L1 and mt p53 and those patients with non-co-expressing(P>0.05).Conclusions TNBC patients with positive mt p53 often simultaneously exhibit positive UCH-L1.TNBC patients with positive UCH-L1 and mt p53 often prone to exhibit higher histological grade,basal-like subtype and worse cell adhesion.UCH-L1 may influence the stability and function of mt p53 by regulating the expression of MDM2,collectively promoting the occurrence and development of TNBC.
作者
魏胜男
吕艳丽
白君
苑晴晴
吴文亚
苏雅洁
Wei Shengnan;Lyu Yanli;Bai Jun;Yuan Qingqing;Wu Wenya;Su Yajie(Department of Pathology,Shunyi Maternal and Children's Hospital of Beijing Children's Hospital,Beijing 101300,China)
出处
《北京医学》
2025年第9期766-771,共6页
Beijing Medical Journal
基金
北京儿童医院顺义妇儿医院妇幼健康基金(Y-FYJK-202404)。
关键词
泛素羧基末端水解酶L1
突变型P53
三阴型乳腺癌
预后
双微体同源基因2
ubiquitin C-terminal hydrolase L1(UCH-L1)
mutant p53(mt p53)
triple negative breast cancer(TNBC)
prognosis
mouse double minute 2(MDM2)
