SOX4与EZH2在乳腺癌组织中的表达及其临床病理意义

发布时间：2019-03-26 19:22

【摘要】：背景:乳腺癌是全球女性最常见的恶性肿瘤之一,患者常因肿瘤转移而死亡。研究表明,SOX4和EZH2均可通过诱导上皮-间质转换(epithelial-mesenchymal transition,EMT)发生,促进肿瘤转移,但在乳腺癌组织中两者表达是否存在一定的相关性仍不清楚。免疫组织化学方法作为病理学诊断的重要辅助手段,可较为简便、直接、特异地检测肿瘤组织中蛋白的表达情况,不仅有助于肿瘤患者包括乳腺癌患者明确诊断,也可在一定程度上评估肿瘤预后,指导临床治疗。目的:观察SOX4和EZH2在乳腺癌组织中的表达情况及相互关系,探讨两者的临床病理意义。方法:采用免疫组织化学方法检测241例乳腺癌组织及126例癌旁非肿瘤乳腺组织中SOX4、EZH2的表达,并检测其中129例乳腺癌组织中EMT标志物E-cadherin、vimentin的表达,显微镜下观察结果并分析SOX4和EZH2表达的相关性及其与乳腺癌临床病理特征的关系,同时分析两者与E-cadherin、vimentin表达的相关性。结果:1.SOX4的表达定位于乳腺上皮细胞及癌细胞的细胞质和(或)细胞核中,在乳腺癌癌巢中呈弥漫均质的表达,高表达率为82.2%(198/241),显著高于癌旁非肿瘤乳腺组织的高表达率57.1%(72/126)(P0.05);2.EZH2的表达定位于乳腺上皮细胞及癌细胞的细胞核中,在乳腺癌癌巢中呈弥漫均质的表达,高表达率为80.1%(193/241),显著高于癌旁非肿瘤乳腺组织的高表达率47.6%(60/126)(P0.05);3.SOX4的高表达与肿瘤淋巴结转移、TNM高分期、HER-2高表达相关(P0.05),随着TNM分期的升高SOX4表达增加(P0.008);4.EZH2的高表达与肿瘤组织学高分级、淋巴结转移、ER阴性、EGFR阳性、高Ki-67增殖指数相关(P0.05);同时EZH2的高表达也与乳腺癌分子分型相关(P0.05),其中EZH2的高表达率在HER-2过表达型中显著高于Luminal A型,差异有统计学意义(P0.008);5.E-cadherin在乳腺癌癌巢中呈异质性表达,其失表达以肿瘤细胞的细胞膜表达缺失为准,梭形、异型明显的肿瘤细胞常失表达E-cadherin,失表达率为50.4%(65/129);vimentin的表达定位于肿瘤细胞的细胞质,在乳腺癌癌巢中呈异质性染色,癌巢中央表达较高,常见于梭形、异型明显的肿瘤细胞,阳性率为73.6%(95/129);6.乳腺癌组织中,E-cadherin与vimentin的表达呈负相关(rs=-0.357,P0.05);SOX4、EZH2均与E-cadherin的表达呈负相关(rs=-0.246,P0.05;rs=-0.357,P0.05),与vimentin的表达呈正相关(rs=0.310,P0.05;rs=0.268,P0.05);7.乳腺癌组织中SOX4与EZH2的表达呈正相关(rs=0.256,P0.05)。结论:SOX4和EZH2在乳腺癌组织中表达上调,两者可能共同参与EMT过程,促进肿瘤淋巴结转移,联合检测SOX4和EZH2,有望成为预测乳腺癌转移的潜在生物学标志物。
[Abstract]:Background: breast cancer is one of the most common malignant tumors in women worldwide. Both SOX4 and EZH2 can promote tumor metastasis by inducing epithelial-interstitial transition (epithelial-mesenchymal transition,EMT), but it is still unclear whether there is a certain correlation between them in breast cancer. As an important auxiliary method for pathological diagnosis, immunohistochemical method can detect the expression of protein in tumor tissue in a simple, direct and specific way, which is not only helpful to the diagnosis of tumor patients, including breast cancer patients, but also helpful to the diagnosis of breast cancer. It can also evaluate the prognosis of tumor to a certain extent and guide the clinical treatment. Objective: to observe the expression and correlation of SOX4 and EZH2 in breast cancer and to explore their clinicopathological significance. Methods: immunohistochemical method was used to detect the expression of SOX4,EZH2 in 241 cases of breast cancer and 126 cases of adjacent non-tumor breast tissue, and the expression of EMT marker E-cadherin and vimentin was detected in 129 cases of breast cancer. The correlation between the expression of SOX4 and EZH2 and the clinicopathological features of breast cancer was observed and analyzed under microscope. The correlation between the expression of VEGF and Vimentin and the expression of E-cadherin and vimentin were also analyzed. Results: the expression of 1.SOX4 was localized in the cytoplasm and / or nucleus of breast epithelial cells and cancer cells. The high expression rate was 82.2% (198 / 241) in breast cancer nests. The high expression rate in non-tumor breast tissues was significantly higher than that in non-tumor breast tissues (72.1%, 72.1%) (P0.05). The expression of 2.EZH2 was localized in the nuclei of breast epithelial cells and cancer cells, and showed diffuse homogenous expression in breast cancer nests, with a high expression rate of 80.1% (1931 / 241). The high expression rate of non-tumor breast tissue was 47.6% (60 / 126) (P0.05). The high expression of 3.SOX4 was correlated with lymph node metastasis, TNM stage and HER-2 expression (P0.05). With the increase of TNM stage, the expression of SOX4 increased (P0.008). The high expression of 4.EZH2 was correlated with high histological grade, lymph node metastasis, ER negative, EGFR positive and high Ki-67 proliferation index (P0.05). At the same time, the high expression of EZH2 was also correlated with molecular typing of breast cancer (P0.05), and the high expression rate of EZH2 was significantly higher than that of Luminal A in the over-expression of HER-2 (P0.05), and the difference was statistically significant (P0.008). The expression of 5.E-cadherin was heterogeneous in breast cancer nests. The loss of 5.E-cadherin expression was based on the loss of cell membrane expression in breast cancer cells, spindle-shaped, and E-cadherin was frequently lost in tumor cells with obvious dysplasia, with a loss of expression rate of 50.4% (65 / 129). The expression of vimentin was localized in the cytoplasm of tumor cells and showed heterogeneous staining in the nests of breast cancer, and the expression was higher in the central part of the nests of breast cancer. The positive rate was 73.6% (95 / 129), and the positive rate was 73.6% (95 / 129). In breast cancer, the expression of E-cadherin was negatively correlated with the expression of vimentin (rs=-0.357,P0.05), and the expression of SOX4,EZH2 was negatively correlated with the expression of E-cadherin (rs=-0.246,P0.05;). Rs=-0.357,P0.05 was positively correlated with the expression of vimentin (rs=0.310,P0.05;rs=0.268,P0.05), 7. There was a positive correlation (rs=0.256,P0.05) between the expression of SOX4 and EZH2 in breast cancer. Conclusion: the expression of SOX4 and EZH2 is up-regulated in breast cancer tissues, both of them may be involved in EMT process and promote lymph node metastasis. Combined detection of SOX4 and EZH2, may be a potential biomarker for predicting breast cancer metastasis.
【学位授予单位】：安徽医科大学
【学位级别】：硕士
【学位授予年份】：2017
【分类号】：R737.9

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