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中华乳腺病杂志(电子版)

中华乳腺病杂志(电子版) ›› 2016, Vol. 10 ›› Issue (05) : 276 -281. doi: 10.3877/cma.j.issn.1674-0807.2016.05.005

论著

ERβ 和PTEN 在人乳腺癌组织中的表达及其临床意义
孙子涵1, 潘沁汶1, 苑龙1, 魏宏屹1, 姜军1,†()   
  1. 1.400038 重庆,第三军医大学西南医院乳腺外科
  • 收稿日期:2016-02-22 出版日期:2016-10-01
  • 通信作者: 姜军

Expressions of ERβ and PTEN in human breast cancer tissue and clinical significance

Zihan Sun1, Qinwen Pan1, Long Yuan1, Hongyi Wei1   

  1. 1.Department of Breast Surgery, Southwest Hospital, Third Military Medical University, Chongqing 400038, China
  • Received:2016-02-22 Published:2016-10-01
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孙子涵, 潘沁汶, 苑龙, 魏宏屹, 姜军. ERβ 和PTEN 在人乳腺癌组织中的表达及其临床意义[J/OL]. 中华乳腺病杂志(电子版), 2016, 10(05): 276-281.

Zihan Sun, Qinwen Pan, Long Yuan, Hongyi Wei. Expressions of ERβ and PTEN in human breast cancer tissue and clinical significance[J/OL]. Chinese Journal of Breast Disease(Electronic Edition), 2016, 10(05): 276-281.

目录

探讨ERβ 和PTEN 在乳腺癌组织中的表达与临床病理特征及患者预后的关系。

方法

回顾性收集2008—2009 年在第三军医大学西南医院乳腺外科手术切除的110 例乳腺癌组织标本,运用免疫组织化学方法检测组织标本中ERβ 和PTEN 的表达。 采用χ2 检验分析其表达与临床病理特征之间的关系,ERβ 和PTEN 相关性分析采用Spearman 方法,运用Kaplan-Meier 生存分析方法分析两者的表达与患者生存的关系。

结果

ERβ 在乳腺癌组织中阳性率为62.7%(69/110),PTEN 在乳腺癌组织中阳性率为59.1%(65/110)。 ERβ 和PTEN 在乳腺癌组织中的表达呈正相关(r=0.276, P=0.003)。 ERβ 的表达与临床分期和淋巴结转移有关(χ2 =11.766,P=0.003;χ2 =9.919,P=0.007)。PTEN 的表达也与与临床分期和淋巴结转移有关(χ2=9.014,P=0.011;χ2=12.201,P=0.002)。 患者随访时间为8 ～70 个月,中位随访时间为39 个月。 生存分析结果显示,ERβ 阳性患者较阴性患者具有更好的5 年DFS(χ2=7.707,P=0.005)。 PTEN 的表达也与较好的5 年DFS 有关(χ2=7.057,P=0.008)。笔者将ERβ 和PTEN 组合起来分为ERβ 阳性PTEN 阴性组(48 例)、ERβ 阴性PTEN 阳性组(17 例)、ERβ 阳性PTEN 阳性组(21 例)以及ERβ 阴性PTEN 阴性组(24 例)4 个组进行生存分析,结果显示:组间差异有统计学意义(χ2=16.790,P＜0.001),ERβ 阴性PTEN 阴性组患者5 年DFS 显著低于ERβ 阴性PTEN 阳性组、ERβ 阳性PTEN 阴性组、ERβ 阳性PTEN 阳性3 个组(χ2 =4.162,P=0.041;χ2 =4.835,P=0.028;χ2=12.640,P＜0.001)。

结论

ERβ 和PTEN 表达均阴性的乳腺癌患者预后较差,两者联合可以作为乳腺癌患者判断预后的分子标记。

关键词: 乳腺肿瘤, 雌激素受体β, PTEN 磷酸水解酶, 预后

Objective

To evaluate the expressions of ERβ and PTEN in human breast cancer tissue,and their correlation with clinicopathological characteristics.

Methods

We retrospectively examined ERβ and PTEN expressions in breast cancer specimens from 110 patients treated in Department of Breast Surgery,Southwest Hospital, Third Military Medical University in 2008-2009 by immunohistochemistry. χ2 test was used to analyze the relationship between the expressions of two factors and the clinicopathological characteristics, Spearman method was used to analyze the correlation between ERβ and PTEN, and Kaplan-Meier survival analysis was used to analyze the relationship between their expressions and patients' survival.

Results

The positive expression rate of ERβ was 62.7%(69/110)and the positive expression rate of PTEN was 59.1%(65/110),indicating a positive correlation between ERβ and PTEN (r=0.276,P=0.003). ERβ expression was associated with TNM stage (χ2=11.766, P=0.003) and lymph node metastasis (χ2=9.919,P=0.007); PTEN expression was also correlated with TNM stage (χ2 =9.014,P=0.011) and lymph node metastasis (χ2=12.201,P=0.002). The patients were followed up for 8-70 months, median 39 months.Survival analysis showed that ERβ positive patients exhibited a better 5-year DFS than those with ERβ negative did (χ2 =7.707,P=0.005), and PTEN positive patients had a better 5-year DFS compared with PTEN negative patients (χ2=7.057,P=0.008). There were 48 patients with ERβ positive and PTEN negative,17 patients with ERβ negative and PTEN positive, 21 patients with ERβ positive and PTEN-positive and 24 patients with ERβ-negative and PTEN-negative. The above-mentioned 4 groups showed a significant difference in DFS(χ2 = 16.790,P＜0.001),DFS in patients with ERβ negative and PTEN negative was significantly lower than that in other 3 groups(χ2=4.162,P=0.041;χ2=4.835,P=0.028;χ2=12.640,P＜0.001).

Conclusion

The breast cancer patients with negative ERβ and PTEN expressions have a poor prognosis, so the two factors can be used as new molecular markers for evaluation of prognosis.

Key words: Breast neoplasms, Estrogen receptor β, PTEN phosphohydrolase, Prognosis
图1 ERβ 和PTEN 在乳腺癌组织中的免疫组织化学染色结果(SP ×200) 注:a、b、c、d 图分别表示ERβ 在乳腺癌组织中评分为1 分(强度0,百分比1)、3 分(强度1,百分比2)、6 分(强度2,百分比4)、8 分(强度3,百分比5);e、f、g、h 图分别表示PTEN 在乳腺癌组织中评分为1 分(强度0,百分比1)、4 分(强度1,百分比3)、6 分(强度2,百分比4)、8 分(强度3,百分比5)
表1 110 例乳腺癌患者临床病理特征与ERβ 和PTEN 表达的关系
临床病理特征 例数 ERβ(例) χ2值 P值 PTEN(例) χ2值 P值
阴性 阳性 阴性 阳性
年龄
＜50岁 58 24 34 0.885 0.347 24 34 0.011 0.916
≥50岁 52 17 35 21 31
临床分期
Ⅰ 49 13 36 11.766 0.003 16 33 9.014 0.011
Ⅱ 50 19 31 20 30
Ⅲ 11 9 2 9 2
肿瘤直径
≤2cm 51 14 37 3.974 0.137 16 35 4.425 0.109
＞2～5cm 53 24 29 25 28
＞5cm 6 3 3 4 2
淋巴结转移
0枚 66 17 49 9.919 0.007 19 47 12.201 0.002
1～3枚 26 13 13 13 13
≥4枚 18 11 7 13 5
ERα
阴性 33 16 17 2.535 0.111 11 22 1.119 0.290
阳性 77 25 52 34 43
PR
阴性 28 13 15 1.347 0.246 11 17 0.041 0.840
阳性 82 28 54 34 48
HER-2
阴性 62 20 42 1.528 0.216 29 33 2.022 0.155
阳性 48 21 27 16 32
表2 110 例乳腺癌组织中ERβ 和PTEN 蛋白表达的相关性分析(例)
PTEN ERβ 合计
阳性 阴性
阳性 48 17 65
阴性 21 24 45
合计 69 41 110
图2 ERβ 和PTEN 表达与乳腺癌患者DFS 的关系 注:a 图表示110 例乳腺癌患者中,ERβ 阳性表达的患者5 年DFS 显著高于ERβ 阴性的患者,χ2 =7.707,P=0.005;b 图表示110 例乳腺癌患者中,PTEN 阳性表达的患者5 年DFS 显著高于ERβ 阴性的患者,χ2=7.057,P=0.008
图3 不同ERβ 与PTEN 表达分组乳腺癌患者DFS 的比较 注:110 例乳腺癌患者中ERβ 阴性PTEN 阴性组比较ERβ 阴性PTEN 阳性组、ERβ 阳性PTEN 阴性组和ERβ 阳性PTEN 阳性组,患者的5 年DFS 最低,χ2=4.162,P=0.041;χ2=4.835,P=0.028;χ2=12.640,P＜0.001
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