乳腺癌组织核蛋白1/p8表达临床意义及其与分子分型的关系

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目的核蛋白1/p8(nuclear protein 1/p8,nupr1/p8)作为转录调节因子,在多种肿瘤中的表达发生了变化。本研究旨在研究乳腺癌组织中nupr1/p8的表达情况,及nupr1/p8的表达与乳腺癌分子分型、临床病理特征的关系及其意义。方法采用免疫组化法检测河北大学附属医院乳腺科2008-01-01-2012-12-01收治的93例乳腺癌组织中nupr1/p8的表达情况,收集同期该院30例非典型导管增生组织和20例良性乳腺病变为对照组,并分析其表达与乳腺癌临床病理学特征(包括肿瘤分级、病理学分期、淋巴结转移、分子分型等)的关系。结果乳腺癌组织中nupr1/p8表达率为63.4%(59/93),显著高于对照组20.0%(10/50),差异有统计学意义,χ~2=24.57,P<0.001;浸润性乳腺癌组织中nupr1/p8表达与淋巴结转移(χ~2=7.75,P=0.005)及分期(χ~2=33.08,P<0.001)有关。淋巴结转移阳性组nupr1/p8高表达率为75.6%(34/45),显著高于淋巴结阴性组43.2%(16/37);Ⅲ期乳腺癌nupr1/p8高表达率为82.6%(19/23),显著高于Ⅰ期55.6%(10/18,χ~2=4.24,P=0.039)及Ⅱ期51.2%(21/41),χ~2=6.19,P=0.013。不同分子分型的浸润性乳腺癌淋巴结转移率不同,χ~2=13.59,P=0.004。人表皮生长因子受体-2(human epidermal growth factor receptor-2,HER2)型淋巴结转移率为70.6%(12/17),显著高于Luminal A型41.7%(15/36),χ~2=3.86,P=0.049;不同分子分型的乳腺癌nupr1/p8高表达率不同,χ~2=10.09,P=0.018。三阴性型nupr1/p8高表达率为83.3%(15/18),显著高于Luminal A型47.2%(17/36,χ~2=6.29,P=0.012)及Luminal B型45.5%(5/11,χ~2=4.58,P=0.032),HER2型nupr1/p8高表达率为76.5%(13/17),显著高于Luminal A型,χ~2=4.02,P=0.044。Nupr1/p8的表达与不同月经状态、组织学类型、组织学分级及肿瘤大小无关,均P>0.05。结论 nupr1/p8在乳腺癌组织中高表达率升高,提示它在乳腺癌发展中可能起重要作用;在肿瘤进展期,nupr1/p8高表达与淋巴结转移及肿瘤分期呈正相关,且与分子分型及预后不良相关,推测nupr1/p8在肿瘤的预后判断中可能为独立因素,检测nupr1/p8的表达水平可能作为乳腺癌预后判断的有用指标。 The nuclear protein 1 / p8 (nuclearprotein1 / p8, nupr1 / p8) as a transcriptional regulator of expression in a variety of tumors has changed. The purpose of this study was to investigate the expression of nupr1 / p8 in breast cancer and the relationship between nupr1 / p8 expression and breast cancer molecular typing and clinicopathological features. Methods Immunohistochemical method was used to detect the expression of nupr1 / p8 in 93 cases of breast cancer admitted to Department of Breast Surgery, Affiliated Hospital of Hebei University from January 2008 to January 12, 2012. Twenty cases of atypical ductal hyperplasia And 20 cases of benign breast lesions as the control group, and analyzed the relationship between the expression and clinical and pathological features of breast cancer (including tumor grade, pathological staging, lymph node metastasis, molecular typing, etc.). Results The positive rate of nupr1 / p8 in breast cancer was 63.4% (59/93), which was significantly higher than that in the control group (20.0%, 10/50) (χ ~ 2 = 24.57, P <0.001) The expression of nupr1 / p8 in breast cancer was correlated with lymph node metastasis (χ ~ 2 = 7.75, P = 0.005) and stage (χ ~ 2 = 33.08, P <0.001). The positive rate of nupr1 / p8 in lymph node positive group was 75.6% (34/45), significantly higher than that in negative group (43.2%, 16/37). The high expression rate of nupr1 / p8 in stage Ⅲ breast cancer was 82.6% (19/23 ) Was significantly higher than that in stage Ⅰ 55.6% (χ ~ 2 = 4.24, P = 0.039) and stage II 51.2% (21/41), χ ~ 2 = 6.19, P = 0.013. Different molecular types of invasive breast cancer lymph node metastasis rate, χ ~ 2 = 13.59, P = 0.004. The lymph node metastasis rate of human epidermal growth factor receptor-2 (HER2) was 70.6% (12/17), significantly higher than that of Luminal A type 41.7% (15/36), χ ~ 2 = 3.86, P = 0.049. The high expression rates of nupr1 / p8 in different molecular types of breast cancer were different (χ ~ 2 = 10.09, P = 0.018). The positive rate of nupr1 / p8 in triple negative type was 83.3% (15/18), which was significantly higher than that in Luminal A type (47.2%, 17/36, χ ~ 2 = 6.29, P = 0.012) 11, χ ~ 2 = 4.58, P = 0.032). The high expression rate of nupr1 / p8 in HER2 was 76.5% (13/17), which was significantly higher than that of Luminal A type (χ ~ 2 = 4.02, P = 0.044). The expression of Nupr1 / p8 had no correlation with different menstrual status, histological type, histological grade and tumor size (P> 0.05). Conclusion The high expression rate of nupr1 / p8 in breast cancer may play an important role in the development of breast cancer. The high expression of nupr1 / p8 is positively correlated with lymph node metastasis and tumor stage in tumor progression, And poor prognosis, it is speculated that nupr1 / p8 may be an independent factor in the prognosis of the tumor. Detecting the expression level of nupr1 / p8 may be used as a useful indicator of the prognosis of breast cancer.
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