目的

旨在通过检测富AT 结合域蛋白1A(ARID1A)在乳腺良恶性肿瘤中的表达差异,探讨其对患者预后的影响。

方法

用随机数字表法选取北京电力医院2009年1月至2015年5月乳腺浸润性导管癌和乳腺纤维腺瘤术后标本各50 例,采用免疫组织化学EnVision 法检测ARID1A 的表达差异。 分析ARID1A 的表达与乳腺癌患者临床病理参数的关系。 以电话及病案查阅的方式了解乳腺癌患者的预后情况,随访日期截止至2015年12月31 日,计算出DFS 和OS。 ARID1A、HER-2、ER 和P53 间的相关性研究采用非参数Spearman 检验。 采用Kaplan-Meier 法进行生存分析,Log-rank 检验进行生存率比较,同时Cox 比例风险回归模型解析影响预后的多种因素。

结果

ARID1A 在50 例乳腺浸润性导管癌中高表达率为46%(23/50),在50 例纤维腺瘤中高表达率为72%(36/50),差异有统计学意义(χ²=6.986, P=0.008)。 在不同母乳喂养时间、组织学分级、P53 表达、ER 表达、PR 表达、分子分型、HER-2 表达的患者中ARID1A 的表达差异亦有统计学意义(χ² =4.177、4.726、4.177、5.469、14.661、5.469,P 均＜0.050)。 ARID1A 的表达与P53 的表达呈正相关(r=0.289,P=0.042),与ER 的表达呈正相关(r=0.331,P=0.019),而与HER-2 的表达呈负相关(r=-0.372,P=0.008)。 TNM Ⅰ、Ⅱ期患者的3年DFS 高于TNM Ⅲ、Ⅳ期(85.5%比42.4%,χ²=9.657,P=0.002),肿瘤直径≤2 cm 的患者的5年OS 高于肿瘤直径＞2 cm 的患者(100%比71.3%,χ²=5.598,P=0.018),P53 阳性组的3年DFS 和5年OS 均高于P53 阴性组(86.3% 比45.5%,χ² =5.077,P=0.024;95.2% 比50.8%,χ² =9.476,P=0.002),ARID1A 高表达患者的3年DFS 和5年OS 均高于ARID1A 低表达患者(81.8%比70.2%,χ²=0.454,P=0.500;90.9%比76.1%,χ²=0.090,P=0.765)。 多变量Cox 回归模型可见P53 阳性表达为影响乳腺癌患者OS 的独立保护性因素(P=0.028,OR=0.079,95%CI:0.008 ～0.761),ARID1A 的表达不是影响OS 的独立预后因素(P=0.194,OR=4.758,95%CI:0.453 ～49.957)。

结论

ARID1A 在乳腺癌组织中的表达低于乳腺纤维腺瘤,可能对乳腺癌的发生发展起重要作用。

Objective

To detect the expression difference of AT-rich interactive domain-containing protein 1A (ARID1A) in malignant and benign breast tumor, and its impact on patients' prognosis.

Methods

The specimens from 50 cases of breast invasive ductal carcinoma and 50 cases of breast fibroma were collected in Beijing Electric Power Hospital between January 2009 and May 2015 by random number table. The expression of ARID1A protein was detected by immunohistochemical EnVision method. The relationship between ARID1A expression and clinicopathological features was analyzed. The 50 breast cancer patients were followed up until December 31, 2015 by phone or reviewing case history. DFS and OS were calculated. The correlations of ARID1A with HER-2, ER and P53 were analyzed by nonparametric Spearman test. Kaplan-Meier method was used for survival analysis and Log-rank test was used to compare the survival rate. Cox proportional hazards regression model was used to analyze the prognostic factors.

Results

The high expression rate of ARID1A was 46% (23/50) in 50 cases of breast invasive ductal carcinoma, and 72% (36/50) in 50 cases of fibroma, indicating a significant difference (χ²=6.986, P=0.008). The expression of ARID1A was significantly different in the patients with different breastfeeding time, histological grade, P53 expression,ER expression, PR expression, molecular types and HER-2 expression (χ²= 4.177,4.726,4.177,5.469,14.661,5.469, P＜0.050). ARID1A expression was positively correlated with P53 (r=0.289, P=0.042)and ER expression (r=0.331, P=0.019), but negatively correlated with HER-2 (r=-0.372, P=0.008).The 3-year DFS in TNM stages Ⅲand Ⅳpatients was significantly higher than that in TNM stage I and Ⅱpatients (85.5% vs 42.4%, χ²=9.657, P=0.002), and 5-year OS in patients with tumor diameter≤2 cm was significantly higher than that in patients with tumor diameter＞2 cm (100% vs 71.3%, χ²=5.598, P=0.018). The 3-year DFS and 5-year OS in P53 positive patients were significantly higher than those in P53 negative patients respectively (86.3% vs 45.5%, χ²= 5.077, P=0.024; 95.2% vs 50.8%, χ²=9.476,P=0.002). The 3-year DFS and 5-year OS in patients with high expression of ARID1A were significantly higher than those in patients with low expression of ARID1A(81.8% vs 70.2%,χ²=0.454,P=0.500;90.9%vs 76.1%,χ² = 0.090,P = 0.765). Multivariable Cox regression model showed that P53 positive was an independent protective factor (P=0.028, OR=0.079,95%CI:0.008-0.761), which could affect the OS of breast cancer patients, but ARID1A expression was not an Independent prognostic factor (P=0.194, OR=4.758,95%CI:0.453-49.957).

Conclusion

The expression of ARID1A in breast cancer tissue is lower than that in breast fibroadenoma, and ARID1A may play an important role in the development of breast cancer.