论著

抑癌基因TP53突变状态与三阴性乳腺癌病人预后的研究

展开
  • 上海交通大学医学院附属瑞金医院外科 腺疾病诊治中心,上海 200025

收稿日期: 2022-08-30

  网络出版日期: 2022-11-10

基金资助

国家自然科学基金(82072937);国家自然科学基金(82072897);上海教育委员会高峰高原计划-研究型医师(20172007)

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

Expand
  • Department of Surgery, Comprehensive Breast Health Center, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 200025, China

Received date: 2022-08-30

  Online published: 2022-11-10

摘要

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。

本文引用格式

杨崔燕, 王豪雨, 陈小松, 沈坤炜 . 抑癌基因TP53突变状态与三阴性乳腺癌病人预后的研究[J]. 外科理论与实践, 2022 , 27(05) : 421 -428 . DOI: 10.16139/j.1007-9610.2022.05.009

Abstract

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 TP53 mutation 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 diffe-rence 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.

参考文献

[1] Sung H, Ferlay J, Siegel RL, et al. Global Cancer Statistics 2020: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries[J]. CA Cancer J Clin, 2021, 71(3):209-249.
[2] Foulkes WD, Smith IE, Reis-Filho JS. Triple-negative breast cancer[J]. N Engl J Med, 2010, 363(20):1938-1948.
[3] Dent R, Trudeau M, Pritchard KI, et al. Triple-negative breast cancer: clinical features and patterns of recurrence[J]. Clin Cancer Res, 2007, 13( <W>15 Pt 1):4429-4434.
[4] Cancer Genome Atlas Network. Comprehensive molecular portraits of human breast tumours[J]. Nature, 2012, 490(7418):61-70.
[5] Boyarskikh UA, Gulyaeva LF, Avdalyan AM, et al. Spectrum of TP53 mutations in BRCA1/2 associated high-grade serous ovarian cancer[J]. Front Oncol, 2020, 10:1103.
[6] Shahbandi A, Nguyen HD, Jackson JG. TP53 mutations and outcomes in breast cancer: reading beyond the headlines[J]. Trends Cancer, 2020, 6(2):98-110.
[7] Hammond ME, Hayes DF, Dowsett M, et al. American Society of Clinical Oncology; College of American Pathologists. American Society of Clinical Oncology/College of American Pathologists guideline recommendations for immunohistochemical testing of estrogen and progesterone receptors in breast cancer (unabridged version)[J]. Arch Pathol Lab Med, 2010, 134(7):e48-e72.
[8] Wolff AC, Hammond MEH, Allison KH, et al. Human epidermal growth factor receptor 2 testing in breast cancer: American Society of Clinical Oncology/College of American Pathologists Clinical Practice Guideline Focused Update[J]. J Clin Oncol, 2018, 36(20):2105-2122.
[9] Amin MB, Greene FL, Edge SB, et al. The Eighth Edition AJCC Cancer Staging Manual: Continuing to build a bridge from a population-based to a more “personalized” approach to cancer staging[J]. CA Cancer J Clin, 2017, 67(2):93-99.
[10] Richards S, Aziz N, Bale S, et al. ACMG Laboratory Quality Assurance Committee. Standards and guidelines for the interpretation of sequence variants: a joint consensus recommendation of the American College of Medical Genetics and Genomics and the Association for Molecular Pathology[J]. Genet Med, 2015, 17(5):405-424.
[11] Tolaney SM, Garrett-Mayer E, White J, et al. Updated standardized definitions for efficacy end points (STEEP) in adjuvant breast cancer clinical trials: STEEP version 2.0[J]. J Clin Oncol, 2021, 39(24):2720-2731.
[12] Basho RK, de Melo Gagliato D, Ueno NT, et al. Clinical outcomes based on multigene profiling in metastatic breast cancer patients[J]. Oncotarget, 2016, 7(47):76362-76373.
[13] Dumay A, Feugeas JP, Wittmer E, et al. Distinct tumor protein p53 mutants in breast cancer subgroups[J]. Int J Cancer, 2013, 132(5):1227-1231.
[14] Bae SY, Nam SJ, Jung Y, et al. Differences in prognosis and efficacy of chemotherapy by p53 expression in triple-negative breast cancer[J]. Breast Cancer Res Treat, 2018, 172(2):437-444.
[15] Olivier M, Langerød A, Carrieri P, et al. The clinical value of somatic TP53 gene mutations in 1,794 patients with breast cancer[J]. Clin Cancer Res, 2006, 12(4):1157-1167.
[16] Pollock NC, Ramroop JR, Hampel H, et al. Differences in somatic TP53 mutation type in breast tumors by race and receptor status[J]. Breast Cancer Res Treat, 2022, 192(3):639-648.
[17] Alexandrova EM, Mirza SA, Xu S, et al. p53 loss-of-heterozygosity is a necessary prerequisite for mutant p53 stabilization and gain-of-function in vivo[J]. Cell Death Dis, 2017, 8(3):e2661.
[18] Hassin O, Nataraj NB, Shreberk-Shaked M, et al. Diffe-rent hotspot p53 mutants exert distinct phenotypes and predict outcome of colorectal cancer patients[J]. Nat Commun, 2022, 13(1):2800.
[19] Li X, Chen X, Wen L, et al. Impact of TP53 mutations in breast cancer: clinicopathological features and prognosis impact of TP53 mutations in breast CA[J]. Thorac Cancer, 2020, 11(7):1861-1868.
[20] Muller PA, Vousden KH. p53 mutations in cancer[J]. Nat Cell Biol, 2013, 15(1):2-8.
[21] Yi Z, Ma F, Rong G, et al. Clinical spectrum and prognostic value of TP53 mutations in circulating tumor DNA from breast cancer patients in China[J]. Cancer Commun (Lond), 2020, 40(6):260-269.
文章导航

/