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中华乳腺病杂志(电子版) ›› 2016, Vol. 10 ›› Issue (03) : 137 -141. doi: 10.3877/cma.j.issn.1674-0807.2016.03.003

论著

乳腺癌组织中白细胞介素8 表达及其临床意义
胡紫叶1, 周昱1, 尼加提·艾尔肯1, 匡夏颖1, 张晋1, 林颖1,()   
  1. 1.510080 广州,中山大学附属第一医院乳腺病诊治中心
  • 收稿日期:2016-02-18 出版日期:2016-06-01
  • 通信作者: 林颖
  • 基金资助:
    广东省企业技术研发与升级改造专项资金项目(2013B021800260)

Expression of interleukin 8 in breast cancer tissue and its clinical significance

Ziye Hu1, Yu Zhou1, Xiaying Kuang1, Jin Zhang1, Ying Lin,1()   

  1. 1.Breast Disease Center, First Affiliated Hospital, Sun Yet-sen University, Guangzhou 510080, China
  • Received:2016-02-18 Published:2016-06-01
  • Corresponding author: Ying Lin
引用本文:

胡紫叶, 周昱, 尼加提·艾尔肯, 匡夏颖, 张晋, 林颖. 乳腺癌组织中白细胞介素8 表达及其临床意义[J/OL]. 中华乳腺病杂志(电子版), 2016, 10(03): 137-141.

Ziye Hu, Yu Zhou, Xiaying Kuang, Jin Zhang, Ying Lin. Expression of interleukin 8 in breast cancer tissue and its clinical significance[J/OL]. Chinese Journal of Breast Disease(Electronic Edition), 2016, 10(03): 137-141.

目的

探讨乳腺癌组织中IL-8 表达与临床病理特征的关系及其对患者长期预后的影响。

方法

回顾性分析1995 年1 月至2007 年12 月中山大学附属第一医院296 例术前未经过任何治疗的浸润性乳腺癌患者的临床资料。 同时收集患者的石蜡标本制作组织芯片,但在芯片制作过程中,有79 例因组织块过小或脱落未能获得准确数据,故实际纳入分析的样本量为217 例。 利用组织芯片技术及免疫组织化学染色方法检测217 例乳腺癌组织中IL-8 的表达,并采用χ2 检验分析IL-8 表达与乳腺癌临床病理特征的关系,用Kaplan-Meier 法进行生存分析,用Log-rank 检验分析IL-8 阳性者与阴性者之间DFS 及OS 的差异,用多因素Cox 回归分析IL-8 表达对患者DFS 的影响。

结果

217 例乳腺癌组织中,IL-8 表达阳性者共59 例,约占27.2%(59/217)。 乳腺癌组织中IL-8 的表达与患者肿瘤T 分期、淋巴结转移状态、ER 和PR 状态存在联系(χ2 =11.208、5.516、55.642、19.706,P 均<0.050)。 单因素分析显示,IL-8 阳性乳腺癌患者5 年及10 年DFS 率分别为83.6%和66.7%,而IL-8 阴性乳腺癌患者5 年及10 年DFS 率分别为95.4% 和87.2%。 IL-8 阳性者DFS 率明显低于IL-8 阴性者(χ2 =8.564,P=0.003),但IL-8 表达对患者OS 的影响尚不明确(χ2=2.460,P=0.117)。 多因素分析显示,IL-8 是影响乳腺癌患者DFS 的独立危险因素(HR=2.450,95%CI:1.117 ~5.376,P=0.025)。 并且,在已绝经的乳腺癌患者中,IL-8 阳性患者较阴性患者具有更大的疾病进展风险(HR=4.526,95%CI:1.706 ~12.006,P=0.002)。

结论

IL-8 可以作为判断乳腺癌患者预后的参考指标之一。 IL-8 阳性者提示预后较差,并且在绝经后的乳腺癌患者中其参考价值更大。

Objective

To investigate the correlation between interleukin-8 (IL-8) in breast cancer tissue and clinicopathological characteristics and the impact of IL-8 on long-term prognosis in breast cancer patients.

Methods

Clinical data of 296 patients with invasive breast cancer without any treatment before operation in the First Affiliated Hospital of Sun Yet-sen University from January 1995 to December 2007 were analyzed retrospectively. At the same time, the paraffin-embedded samples were collected to make tissue microarray. Totally 217 patients were included in this study and 79 patients were excluded from the study because of small or abscised samples. The expression of IL-8 in 217 cases of breast cancer was detected by tissue microarray technique and immunohistochemical staining. χ2 test was used to analyze the relationship between IL-8 expression and clinical characteristics of breast cancer. Kaplan-Meier method was used for survival analysis, and the differences of DFS and OS between IL-8 positive and IL-8 negative patients were analyzed by Log-rank test. Cox regression model was applied to demonstrate the impact of IL-8 on DFS.

Results

IL-8 expression was positive in 59 cases, accounting for about 27.2% of 217 cases in total. The expression of IL-8 was related to tumor stage, lymph node status, ER and PR status (χ2 =11.208, 5.516,55.642,19.706,allP<0.050). Univariable analysis showed that 5-year and 10-year DFS were 83.6% and 66.7% in IL-8 positive patients, 95.4% and 87.2% in IL-8 negative patients respectively. DFS in IL-8 positive patients was significantly lower than that in IL-8 negative patients (χ2=8.564,P=0.003), while IL-8 had indefinite impact on OS (χ2=2.460, P=0.117). Multivariable analysis identified IL-8 as an independent risk factor of DFS (HR=2.450,95%CI:1.117-5.376,P=0.025). In postmenopausal patients,IL-8 positive patients had a higher risk of disease progression than IL-8 negative patients did (HR=4.526,95%CI:1.706-12.006,P=0.002).

Conclusion

IL-8 could be a prognostic index of breast cancer patients and IL-8 positive expression indicates a poor prognosis, especially in postmenopausal patients.

表1 乳腺癌患者无瘤生存Cox 回归分析变量赋值表
图1 乳腺癌组织中IL-8 免疫组织化学染色结果(SP ×200) 注:a 图显示IL-8 阳性表达;b 图显示IL-8 阴性表达
表2 217 例乳腺癌患者临床特征与IL-8 表达的关系
图2 217 例乳腺癌患者IL-8 表达相关的DFS 曲线 注:IL-8 阳性与阴性乳腺癌患者间DFS 率相比,差异有统计学意义,χ2=8.564,P=0.003
图3 217 例乳腺癌患者IL-8 表达相关的OS 曲线 注:IL-8 阳性与阴性乳腺癌患者间OS 率相比,差异无统计学意义,χ2=2.460,P=0.117
表3 217 例乳腺癌患者IL-8 表达相关DFS 的Cox 多因素回归分析
表4 分层分析IL-8 表达对不同月经状态乳腺癌患者DFS 的影响(n=217)
[1]
Torre LA, Bray F, Siegel RL, et al. Global cancer statistics, 2012[J]. CA Cancer J Clin,2015,65(2):87-108.
[2]
Yoshimura T, Matsushima K, Tanaka S, et al. Purification of a human monocyte-derived neutrophil chemotactic factor that has peptide sequence similarity to other host defense cytokines[J]. Proc Natl Acad Sci U S A,1987,84(24):9233-9237.
[3]
Freund A, Chauveau C, Brouillet JP, et al. IL-8 expression and its possible relationship with estrogen-receptor-negative status of breast cancer cells[J]. Oncogene,2003,22(2):256-265.
[4]
Lin Y, Huang R, Chen L, et al. Identification of interleukin-8 as estrogen receptor-regulated factor involved in breast cancer invasion and angiogenesis by protein arrays[J]. Int J Cancer,2004,109 (4):507-515.
[5]
Yao C, Lin Y, Chua MS, et al. Interleukin-8 modulates growth and invasiveness of estrogen receptor-negative breast cancer cells[J]. Int J Cancer,2007,121(9):1949-1957.
[6]
Shao N, Chen L, Ye R, et al. The depletion of interleukin-8 causes cell cycle arrest and increases the efficacy of docetaxel in breast cancer cells[J]. Biochem Bioph Res Commun,2013,431(3):535-541.
[7]
Shao N, Lu Z, Zhang Y, et al. Interleukin-8 upregulates integrin β3 expression and promotes estrogen receptor-negative breast cancer cell invasion by activating the PI3K/Akt/NF-κB pathway[J]. Cancer Lett,2015,364(2):165-172.
[8]
姚陈,王深明,谢丹,等. 白细胞介素-8 的表达与乳腺癌预后的关系[J]. 中华外科杂志,2006,44(13):900-903.
[9]
Hammond ME, Hayes DF, Dowsett M, et al. American Society of Clinical Oncology/College of American Pathologists guideline recommendations for immunohistochemical testing of estrogen and progesterone receptors in breast cancer[J]. J Clin Oncol,2010,28(16):2784-2795.
[10]
Fridlender ZG, Albelda SM, Granot Z. Promoting metastasis:neutrophils and T cells join forces[J]. Cell Res,2015,25(7):765-766.
[11]
Kalluri R, Weinberg RA. The basics of epithelial-mesenchymal transition [J]. J Clin Invest,2009,119(6):1420-1428.
[12]
Grivennikov SI, Greten FR, Karin M. Immunity, inflammation, and cancer [J]. Cell,2010,140(6):883-899.
[13]
Araki S, Omori Y, Lyn D, et al. Interleukin-8 is a molecular determinant of androgen independence and progression in prostate cancer [J]. Cancer Res,2007,67(14):6854-6862.
[14]
Kunz M, Hartmann A,Flory E,et al. Anoxia-induced up-regulation of interleukin-8 in human malignant melanoma. A potential mechanism for high tumor aggressiveness[J]. Am J Pathol,1999,155(3):753-763.
[15]
Xiao YC, Yang ZB, Cheng XS, et al. CXCL8, overexpressed in colorectal cancer, enhances the resistance of colorectal cancer cells to anoikis[J]. Cancer Lett,2015,361(1):22-32.
[16]
Cheng XS, Li YF, Tan J, et al. CCL20 and CXCL8 synergize to promote progression and poor survival outcome in patients with colorectal cancer by collaborative induction of the epithelialmesenchymal transition[J]. Cancer Lett,2014,348(1/2):77-87.
[17]
Reis ST, Leite KR, Piovesan LF, et al. Increased expression of MMP-9 and IL-8 are correlated with poor prognosis of bladder cancer[J]. BMC Urol,2012,12:18.
[18]
Slattery ML, Herrick JS, Torres-Mejia G, et al. Genetic variants in interleukin genes are associated with breast cancer risk and survival in a genetically admixed population: the breast cancer health disparities study[J]. Carcinogenesis,2014,35(8):1750-1759.
[19]
Yokoe T, Iino Y, Morishita Y. Trends of IL-6 and IL-8 levels in patients with recurrent breast cancer: preliminary report[J]. Breast Cancer,2000,7(3):187-190.
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