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热休克蛋白27和大汗腺型乳腺癌囊液蛋白15在分子性大汗腺型乳腺癌中发挥关键作用。

Heat shock protein 27 and gross cystic disease fluid protein 15 play critical roles in molecular apocrine breast cancer.

作者信息

Liu Xiaozhen, Feng Changyun, Liu Junjun, Zhao Lin, Liu Jian, Zhang Wei, Liu Ning, Niu Yun

机构信息

Tianjin Medical University Cancer Institute and Hospital, National Clinical Research Center for Cancer, Key Laboratory of Cancer Prevention and Therapy of Tianjin, Key Laboratory of Breast Cancer Prevention and Therapy, Tianjin Medical University, Ministry of Education, West Huanhu Road, Ti Yuan Bei, Hexi District, Tianjin, 300060, China.

Department of Maternal and Child Health Hospital, North China University of Science and Technology, 14, Jianshe-South Road, Lubei District, Tangshan, 063000, China.

出版信息

Tumour Biol. 2016 Jun;37(6):8027-36. doi: 10.1007/s13277-015-4712-4. Epub 2015 Dec 28.

DOI:10.1007/s13277-015-4712-4
PMID:26711786
Abstract

Molecular apocrine breast cancer (MABC) has a distinct hormonal profile, being estrogen receptor (ER) and progesterone receptor (PR) negative but androgen receptor (AR) positive. The clinical significance of MABC and its relative variables have not been absolutely clarified and remain to be determined. Five hundred cases of invasive breast carcinoma were randomly selected in this study, including 158 MABC cases and 342 nonMABC cases. Expression of ER, PR, epidermal growth factor receptor 2 (HER2), Ki67, AR, gross cystic disease fluid protein 15 (GCDFP15), and heat shock protein 27 (HSP27) were analyzed by immunohistochemistry. Differences of continuous variables between MABC and nonMABC subgroups were evaluated by the chi-square test. The Kaplan-Meier method was performed to evaluate disease-free survival (DFS) and overall survival (OS). The MABC subgroup had higher histological grade, bigger tumor size, more lymph node metastasis, and higher pTNM stage than the nonMABC subgroup (P < 0.05), and patients with MABC had poorer prognosis than those of the nonMABC subgroup (P < 0.05). Both GCDFP15 and HSP27 were expressed differently in the MABC and nonMABC subgroups (P < 0.05). Furthermore, in the MABC subgroup, positive HSP27 expression indicated higher risk of recurrence (P < 0.05) and positive GCDFP15 expression was also a poor marker for patient outcome (P < 0.05). MABC patients with HSP27 and GCDFP15 co-expression had worse outcome (P < 0.05). Our data suggested that MABC had a high risk of recurrence. Positive expression of both GCDFP15 and HSP27 were correlated with MABC malignancy. Targeting AR and HSP27 at the same time might offer a useful strategy to MABC.

摘要

分子型大汗腺癌(MABC)具有独特的激素谱,雌激素受体(ER)和孕激素受体(PR)呈阴性,但雄激素受体(AR)呈阳性。MABC及其相关变量的临床意义尚未完全阐明,仍有待确定。本研究随机选取500例浸润性乳腺癌病例,其中包括158例MABC病例和342例非MABC病例。采用免疫组织化学法分析ER、PR、表皮生长因子受体2(HER2)、Ki67、AR、巨大囊肿病液体蛋白15(GCDFP15)和热休克蛋白27(HSP27)的表达情况。采用卡方检验评估MABC和非MABC亚组之间连续变量的差异。采用Kaplan-Meier法评估无病生存期(DFS)和总生存期(OS)。MABC亚组的组织学分级更高、肿瘤尺寸更大、淋巴结转移更多且pTNM分期更高,高于非MABC亚组(P < 0.05),MABC患者的预后比非MABC亚组患者更差(P < 0.05)。GCDFP15和HSP27在MABC和非MABC亚组中的表达均存在差异(P < 0.05)。此外,在MABC亚组中,HSP27阳性表达表明复发风险更高(P < 0.05),GCDFP15阳性表达也是患者预后不良的指标(P < 0.05)。HSP27和GCDFP15共表达的MABC患者预后更差(P < 0.05)。我们的数据表明,MABC具有较高的复发风险。GCDFP15和HSP27的阳性表达均与MABC的恶性程度相关。同时靶向AR和HSP27可能为MABC提供一种有用的策略。

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本文引用的文献

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Tumour Biol. 2015 Apr;36(4):2241-8. doi: 10.1007/s13277-014-2652-z. Epub 2015 Mar 24.
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Gross cystic disease fluid protein 15 (GCDFP-15) expression in breast cancer subtypes.乳腺囊肿病液体蛋白15(GCDFP-15)在乳腺癌亚型中的表达。
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Epidermal growth factor/heat shock protein 27 pathway regulates vasculogenic mimicry activity of breast cancer stem/progenitor cells.
表皮生长因子/热休克蛋白27通路调控乳腺癌干/祖细胞的血管生成拟态活性。
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Heat-shock protein beta 1 regulates androgen-mediated bovine myogenesis.热休克蛋白β1调节雄激素介导的牛肌肉生成。
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Molecular apocrine breast cancers are aggressive estrogen receptor negative tumors overexpressing either HER2 or GCDFP15.分子顶泌型乳腺癌是侵袭性雌激素受体阴性肿瘤,过度表达HER2或GCDFP15。
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Suppression of heat shock protein 27 induces long-term dormancy in human breast cancer.抑制热休克蛋白 27 诱导人乳腺癌的长期休眠。
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