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中华乳腺病杂志(电子版)

中华乳腺病杂志(电子版) ›› 2020, Vol. 14 ›› Issue (01) : 44 -49. doi: 10.3877/cma.j.issn.1674-0807.2020.01.011

所属专题： 文献；

论著

p53凋亡刺激蛋白家族成员在浸润性乳腺癌中的表达及其意义
马文凤1, 张辉2, 范乃军1, 李富林1, 蒙念龙1, 原旭涛1, 王长松1,†()   
  1. 1. 471031　洛阳，解放军第九八九医院病理科
    2. 471031　洛阳，解放军第九八九医院乳腺外科
  • 收稿日期:2017-07-19 出版日期:2020-02-01
  • 通信作者: 王长松
  • 基金资助:
    洛阳市科技计划基金资助项目(1603003A-13)

Expression of apoptosis-stimulating protein of p53 family members in invasive breast cancer and its prognostic significance

Wenfeng Ma1, Hui Zhang2, Naijun Fan1, Fulin Li1, Nianlong Meng1, Xutao Yuan1, Changsong Wang1,†()   

  1. 1. Department of Pathology, No. 989 Hospital of PLA, Luoyang 471031, China
    2. Department of Breast Surgery, No. 989 Hospital of PLA, Luoyang 471031, China
  • Received:2017-07-19 Published:2020-02-01
  • Corresponding author: Changsong Wang
  • About author:
    Corresponding author: Wang Changsong, Email:
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引用本文：

马文凤, 张辉, 范乃军, 李富林, 蒙念龙, 原旭涛, 王长松. p53凋亡刺激蛋白家族成员在浸润性乳腺癌中的表达及其意义[J]. 中华乳腺病杂志(电子版), 2020, 14(01): 44-49.

Wenfeng Ma, Hui Zhang, Naijun Fan, Fulin Li, Nianlong Meng, Xutao Yuan, Changsong Wang. Expression of apoptosis-stimulating protein of p53 family members in invasive breast cancer and its prognostic significance[J]. Chinese Journal of Breast Disease(Electronic Edition), 2020, 14(01): 44-49.

目的

研究p53凋亡刺激蛋白(ASPP)家族成员在浸润性乳腺癌中的表达，并探讨其与p53表达状态、乳腺癌分子分型及预后的关系。

方法

收集2005年1月至2010年4月解放军第九八九医院收治的155例浸润性乳腺癌患者组织标本进行回顾性分析。采用免疫组织化学方法检测组织标本中ASPP1、ASPP2、P53凋亡刺激蛋白抑制因子(iASPP)、p53、ER、PR、HER-2和Ki67的表达，并用χ2检验分析ASPP家族成员表达与乳腺癌分子分型和p53状态的关系，采用Kaplan-Meier生存分析方法评价ASPP家族成员表达与患者预后的关系。

结果

155例乳腺癌组织中，ASPP1阳性率为13.5%(21/155)，ASPP2阳性率为97.4%(151/155)，iASPP阳性率为61.3%(95/155)。表达野生型p53者33例，突变型p53者122例，p53的突变率为78.7%(122/155)。ASPP家族成员的表达在野生型p53组与突变型p53组间差异无统计学意义(ASPP1：χ2<0.001，P＝0.987; ASPP2：χ2＝1.110，P＝0.579; iASPP：χ2＝0.244，P＝0.621)。luminal A型44例，luminal B型66例，basal-like型18例，HER-2过表达型27例，ASPP家族成员的表达在不同分子分型乳腺癌组间差异无统计学意义(ASPP1：χ2＝2.325, P＝0.508; ASPP2：χ2＝1.657, P＝0.642; iASPP: χ2＝0.815，P＝0.846)。随访时间2～108个月，中位随访时间66个月，患者3年总生存率为84.5%(131/155)，5年OS率为79.4%(123/155)。ASPP1、ASPP2和iASPP表达阳性组与阴性组相比，患者5年OS率的差异均无统计学意义(ASPP1：χ2＝3.790, P＝0.050；ASPP2：χ2＝0.040, P＝0.927；iASPP：χ2＝1.253, P＝0.263)。

结论

ASPP家族成员在浸润性乳腺癌中的表达与P53突变、乳腺癌分子分型以及乳腺癌患者预后均无关。

关键词: 乳腺肿瘤, 细胞凋亡, 分子分型, 预后, 肿瘤抑制蛋白p53
Objective

To explore the expression of apoptosis-stimulating protein of p53 (ASPP) family members in invasive breast cancer and their relationship with p53 expression, molecular subtype and prognosis of patients.

Methods

The tissue samples from 155 invasive breast cancer patients in the Department of Pathology, No. 989 Hospital of PLA from January 2005 to April 2010 were analyzed retrospectively. The expression of ASPP family members (ASPP1, ASPP2, iASPP), p53, ER, PR, HER-2 and Ki67 in breast cancer tissue samples was detected by immunohistochemistry. The relationship between the expression of ASPP family members and different molecular subtypes or p53 expression were analyzed by χ2 test, and the Kaplan-Meier method was used to analyze the relationship between expression of ASPP family members and patient survival.

Results

In the invasive breast cancer tissue samples of 155 cases, the positive rate of ASPP1 was 13.5% (21/155), ASPP2 97.4% (151/155), and iASPP 61.3% (95/155). There were 33 cases of wild-type p53 expression and 122 cases of p53 mutation expression, so the mutation rate of p53 was 78.7% (122/155). There was no significant difference in the expression of ASPP family members between the wild-type p53 expression group and p53 mutation group (ASPP1: χ2<0.001, P=0.987; ASPP2: χ2=1.110, P=0.579; iASPP: χ2=0.244, P=0.621). There were 44 patients with luminal A subtype breast cancer, 66 luminal B, 18 basal-like and 27 HER-2 over-expression in all 155 patients, suggesting no significant difference in the expression of ASPP family members across different subtypes(ASPP1: χ2=2.325, P=0.508; ASPP2: χ2=1.657, P=0.642; iASPP: χ2=0.815, P=0.846). The patients were followed up for 2-108 months, median 66 months. The 3-year survival rate was 84.5% (131/155) and 5-year survival rate was 79.4% (123/155). There was no significant difference between ASPP1/ASPP2/iASPP positive group and negative group in the 5-year survival (ASPP1: χ2=3.790, P=0.050; ASPP2: χ2=0.040, P=0.927; iASPP: χ2=1.253, P=0.263).

Conclusions

The expression of ASPP family members in invasive breast cancer is not related to p53 mutation, molecular subtype and survival.

Key words: Breast neoplasms, Apoptosis, Molecular typing, Prognosis, Tumor suppressor protein p53
图1 乳腺癌组织中p53凋亡刺激蛋白1阳性表达(SP ×20)
图2 乳腺癌组织中p53凋亡刺激蛋白2阳性表达(SP ×10)
图3 乳腺癌组织中p53凋亡刺激蛋白抑制因子阳性表达(SP ×20)
表1 p53野生型与突变型乳腺癌患者ASPP家族成员表达的比较(例)
p53表达 例数 ASPP1 ASPP2 iASPP
阳性 阴性 阳性 阴性 阳性 阴性
野生型 33 5 28 33 0 19 14
突变型 122 16 106 118 4 76 46
χ2值 ? <0.001 1.110 0.244
P值 ? 0.987 0.579 0.621
图4 乳腺癌组织中野生型p53表达(SP ×20)
图5 乳腺癌组织中突变型p53表达(SP ×20)　a图所示90%以上癌细胞的细胞核出现棕黄色颗粒；b图所示无细胞核出现棕黄色颗粒
表2 不同分子分型乳腺癌组织中ASPP家族成员的表达(例)
分子分型 例数 ASPP1 ASPP2 iASPP
阳性 阴性 阳性 阴性 阳性 阴性
luminal A 44 8 36 42 2 28 16
luminal B 66 8 58 65 1 38 28
HER-2过表达 27 5 22 26 1 18 9
basal-like型 18 1 17 18 0 11 7
χ2值 ? 2.325 1.657 0.815
P值 ? 0.508 0.642 0.846
图6 乳腺癌患者5年总生存率与ASPP家族成员表达的关系　a、b、c图分别为不同ASPP1、ASPP2及iASPP表达的乳腺癌患者5年总生存曲线
[1]
Wang C, Gao C, Chen Y, et al. Expression pattern of the apoptosis-stimulating protein of p53 family in p53＋ human breast cancer cell lines [J]. Cancer Cell Int, 2013, 13(1)：116.
[2]
Xie XF, Yang Q, Chi J, et al. Prognostic values of apoptosis-stimulating P53-binding protein 1 and 2 and their relationships with clinical characteristics of esophageal squamous cell carcinoma patients: a retrospective study [J]. Chin J Cancer，2017, 36(1)：15.
[3]
Alkushi A, Lim P, Coldman A, et al. Interpretation of p53 immunoreactivity in endometrial carcinoma: establishing a clinically relevant cut-off level [J]．Int J Gynecol Pathol, 2004, 23(2): 129-137.
[4]
《乳腺癌HER2检测指南(2014版)》编写组．乳腺癌HER2检测指南(2014版)[J]．中华病理学杂志，2014，43(4)：262-267.
[5]
Gresham D. Cheating death [J]. Nat Rev Mol Cell Biol, 2003, 4(2)：87.
[6]
Liu ZJ，Lu X, Zhong S. ASPP-apoptotic specific regulator of p53 [J]. Biochim Biophys Acta, 2005, 1756(1)：77-80.
[7]
王长松，李红，高春芳，等. iASPP对表达野生型p53基因的乳腺癌细胞株MCF-7凋亡的影响[J]. 中国病理生理杂志， 2010，26(2): 282-286.
[8]
Qiu S, Cai Y, Gao X, et al. A small peptide derived from p53 linker region can resume the apoptotic activity of p53 by sequestering iASPP with p53 [J]. Cancer Lett, 2015，356 (2 Pt B): 910-917.
[9]
Li G，Wang R，Gao J，et al. RNA interference-mediated silencing of IASPP induces cell proliferation inhibition and G0/G1 cell cycle arrest in u251 human glioblastoma cells [J]. Mol Cell Biochem, 2011，350(1-2)：193-200.
[10]
Jia Y, Peng L, Rao Q, et al. Oncogene iASPP enhances self-renewal of hematopoietic stem cells and facilitates their resistance to chemotherapy and irradiation [J]. FASEB J, 2014, 28: 2816-2827.
[11]
Chan KK, Wong ES, Wong IT, et al. Overexpression of iASPP is required for autophagy in response to oxidative stress in choriocarcinoma [J]. BMC Cancer, 2019, 19(1)：953-965.
[12]
Robinson RA, Lu X, Jones EY, et al. Biochemical and structural studies of ASPP proteins reveal differential binding to p53, p63, and p73 [J]. Structure, 2008, 16 (2)：259-268.
[13]
Wang Y, Godin-Heymann N, Dan Wang X, et al. ASPP1 and ASPP2 bind active RAS, potentiate RAS signalling and enhance p53 activity in cancer cells [J]. Cell Death Differ, 2013，20(4): 525-534.
[14]
Ao Y, Rohde LH, Naumovski L. P53-interacting protein 53BP2 inhibits clonogenic survival and sensitizes cells to doxorubicin but not paclitaxel-induced apoptosis [J]. Oncogen, 2001, 20 (21): 2720-2725.
[15]
Chikh A, Matin RN, Senatore V, et al. iASPP/p63 autoregulatory feedback loop is required for the homeostasis of stratified epithelia [J]. EMBO J, 2011, 30(20)：4261-4273.
[16]
Lossos IS, Natkunam Y，Levy R, et al. Apoptosis stimulating protein of p53(ASPP2) expression differs in diffuse large B-cell and follicular center lymphoma：corelation with clinical outcome [J]. Leuk Lympoma, 2002, 43(12)：2309-2317.
[17]
Pang Y, Pan L, Zhang Y, et al. TP53BP2 decreases cell proliferation and induces autophagy in neuroblastoma cell lines [J]. Oncol Lett, 2019，17(6): 4976-4984.
[18]
Kong F, Shi X, Li H, et al. Increased expression of iASPP correlates with poor prognosis in FIGO IA2-IIA cervical adenocarcinoma following a curative resection[J]. Am J Cancer Res, 2015, 5(3)：1217-1224.
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