抑癌基因TP53突变状态与三阴性乳腺癌病人预后的研究

Study on tumour suppressor gene TP53 mutation and prognosis in patients with triple-negative breast cancer

目的:分析三阴性乳腺癌(triple-negative breast cancer, TNBC)病人抑癌基因TP53突变情况、临床病理特征及其预后。方法:回顾性分析2012年1月至2019年3月于本院乳腺疾病诊治中心手术的早期TNBC病人,分析TP53基因突变频率和类型、临床病理特征及其预后。结果:234例TNBC病人分为144例(61.54%)TP53基因突变型组和90例(38.46%)TP53野生型组。大多数TP53基因突变在第5~8外显子区域,进一步分为错义突变85例(59.03%)和非错义突变59例(40.97%)。与TP53野生型病人比较,TP53突变型的细胞增殖抗原(Ki-67)高表达(>30%)病人较多(80.56%比63.33%,P=0.004,OR=2.40)。突变型组与野生型组的无复发生存期(P=0.447)、总生存期(P=0.083)和远处无复发生存期(P=0.131)差异均无统计学意义。同样,病人TP53错义突变与非错义突变之间的预后差异亦无统计学意义,分别为无复发生存期P=0.226,总生存期P=0.885,远处无复发生存期P=0.172。结论:TNBC病人的TP53突变与较高Ki-67表达相关,但TP53突变型病人预后与野生型病人相似。

Objective To investigate tumour suppressor gene TP53 mutation, clinicopathological features and prognosis in the patients with triple-negative breast cancer(TNBC). Methods The rate and distribution of TP53 mutation, clinicopathological features, and prognosis in the patients with TNBC and with surgery at our center from January 2012 to March 2019 were retrospectively analyzed. Results In total of 234 TNBC cases, 144(61.54%) cases were with TP53 mutation type and 90(38.46%) cases with TP53 wild type. Most mutation was located at exon 5-8 region. The cases with TP53mutation were divided into the group of missense mutation 85(59.03%) cases and the group of non-missense mutation 59(40.97%) cases. More cases with TP53 mutation type had higher proliferation antigen(Ki-67) expression(>30%) when compared with the cases with TP53 wild type(80.56% vs. 63.33%, P=0.004, OR=2.40). There was no significant difference in prognosis between the group of mutation type and the group of wild type in relapse-free survival(RFS)(P=0.447),overall survival(OS)(P=0.083), and distant relapse-free survival(DRFS)(P=0.131). Similarly, there was no significant difference in prognosis between TP53 missense mutation and non-missense mutation in RFS(P=0.226), OS(P=0.885), and DRFS(P =0.172). Conclusions TNBC patients with TP53 mutation exhibited higher Ki-67 expression, however, similar prognosis between TP53 mutation type and wild type.