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中华乳腺病杂志(电子版)

中华乳腺病杂志(电子版) ›› 2020, Vol. 14 ›› Issue (04) : 234 -239. doi: 10.3877/cma.j.issn.1674-0807.2020.04.007

所属专题： 总编推荐； 文献；

论著

新疆地区乳腺癌患者复发、转移灶与原发灶分子标志物表达差异及分子亚型转型
赵振慧1, 李妍1, 刘炜1, 马小平1, 李红玉1, 李莉1, 高春燕1, 刘丹1, 李迅1,†()   
  1. 1. 830011　乌鲁木齐，新疆医科大学附属肿瘤医院乳腺内科
  • 收稿日期:2019-05-15 出版日期:2020-08-01
  • 通信作者: 李迅
  • 基金资助:
    新疆医科大学科研创新基金资助项目(XYDCX201671)

Difference in expression of molecular markers between primary lesions and recurrent/metastatic lesions and transformation of molecular subtypes in breast cancer patients in XinJiang region

Zhenhui Zhao1, Yan Li1, Wei Liu1, Xiaoping Ma1, Hongyu Li1, Li Li1, Chunyan Gao1, Dan Liu1, Xun Li1,†()   

  1. 1. Department of Breast Internal Medicine, Affiliated Cancer Hospital of Xinjiang Medical University, Urumqi 830011, China
  • Received:2019-05-15 Published:2020-08-01
  • Corresponding author: Xun Li
  • About author:
    Corresponding author: Li Xun, Email:
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引用本文：

赵振慧, 李妍, 刘炜, 马小平, 李红玉, 李莉, 高春燕, 刘丹, 李迅. 新疆地区乳腺癌患者复发、转移灶与原发灶分子标志物表达差异及分子亚型转型[J]. 中华乳腺病杂志(电子版), 2020, 14(04): 234-239.

Zhenhui Zhao, Yan Li, Wei Liu, Xiaoping Ma, Hongyu Li, Li Li, Chunyan Gao, Dan Liu, Xun Li. Difference in expression of molecular markers between primary lesions and recurrent/metastatic lesions and transformation of molecular subtypes in breast cancer patients in XinJiang region[J]. Chinese Journal of Breast Disease(Electronic Edition), 2020, 14(04): 234-239.

目的

探讨乳腺癌患者复发、转移灶与原发灶中分子标志物ER、PR、HER-2、Ki67、p53的表达差异以及乳腺癌分子亚型的转型。

方法

本研究为双向队列研究，选取新疆医科大学附属肿瘤医院2017年5月至2019年5月收治的首次出现局部复发或远处转移的女性乳腺癌患者，对入组患者采用手术或穿刺活组织检查检测其复发、转移灶中ER、PR、HER-2、Ki67、p53的表达，并回顾患者初次诊断时原发灶中各指标表达情况，采用配对χ2检验对复发、转移灶和原发灶的ER、PR、HER-2、Ki67、p53表达进行比较。

结果

共纳入103例乳腺癌复发、转移患者。原发灶中ER、PR、HER-2及p53阳性率分别为63.1%(65/103)、55.3%(57/103)、31.1%(32/103)和68.9%(71/103)，Ki67高表达(>14%)占68.9%(71/103)；复发、转移灶中ER、PR、HER-2及p53阳性率分别为56.3%(58/103)、42.7%(44/103)、30.1%(31/103)和77.7%(80/103)，Ki67高表达占68.9%(71/103)。103例患者复发、转移灶与原发灶中ER、PR、HER-2、Ki67及p53表达不一致率分别为8.7%(9/103)、16.5%(17/103)、6.8%(7/103)、29.1%(30/103)及14.6%(15/103)。乳腺癌患者复发、转移灶与原发灶的HER-2及Ki67表达比较，差异均无统计学意义(P＝1.000、1.000)，但是，ER、PR及p53表达比较，差异均有统计学意义(P＝0.039、0.002、0.035)。103例患者原发灶与复发、转移灶中luminal A型、luminal B型、HER-2过表达型及三阴性乳腺癌分别占8.7%(9/103)和10.7%(11/103)、54.3%(56/103)和53.4%(55/103)、18.4%(19/103)和14.6%(15/103)、18.4%(19/103)和21.4%(22/103)。复发、转移后luminal A型及三阴性乳腺癌患者比例上升，其余分子亚型比例均下降。乳腺原发肿瘤luminal A型、luminal B型、HER-2过表达型、三阴性乳腺癌病情进展后复发、转移灶发生转型的比例分别占6/9、30.4%(17/56)、7/19、3/19。

结论

乳腺癌复发、转移后ER、PR、HER-2、Ki67、p53表达常发生变化，且分子亚型转变较为常见，可通过了解复发、转移灶的分子表达情况和分子亚型，制定更为精准的治疗方案，提高治疗疗效。

关键词: 乳腺肿瘤, 肿瘤复发, 局部, 肿瘤转移, 基因表达
Objective

To investigate the expression differences of molecular markers ER, PR, HER-2, Ki67 and p53 between primary lesions and recurrent/metastatic lesions and molecular subtype transformation in breast cancer patients in Xinjiang region.

Methods

This study was a two-way cohort study. The female breast cancer patients with first local recurrence or distant metastasis in the Affiliated Cancer Hospital of Xinjiang Medical University from May 2017 to May 2019 was enrolled in this study. The expression of ER, PR, HER-2, Ki67, and p53 in recurrent/metastatic lesions was detected with the samples obtained by surgery or aspiration biopsy. Meanwhile the clinical data of patients before recurrence or metastasis was retrospectively analyzed to extract the expression of ER, PR, HER-2, Ki67, and p53 in primary lesions. The paired χ2 test was used to compare the expressions of ER, PR, HER-2, Ki67, and p53 between recurrent/metastatic lesions and primary lesions.

Results

Totally 103 patients were enrolled. In primary lesions, the positive rates of ER, PR, HER-2 and p53 were 63.1%(65/103), 55.3%(57/103), 31.1%(32/103)and 68.9%(71/103), and the high expression of Ki67 (>14%) accounted for 68.93%(71/103)of the total. In recurrent/metastatic lesions, the positive rates of RR, PR, HER-2 and p53 in recurrent/metastatic lesions were 56.3%(58/103), 42.7%(44/103), 30.1%(31/103)and 77.7%(80/103), and the high expression of Ki67 accounted for 68.9%(71/103)of total. The rates of expression change of ER, PR, HER-2, Ki67 and p53 were 8.7%(9/103), 16.5%(17/103), 6.8%(7/103), 29.1%(30/103)and 14.6%(15/103). There was no significant difference in the expression of HER-2 and Ki67 between recurrent/metastatic lesions and primary lesions (P=1.000, 1.000), while the expression of ER, PR and p53 presented a significant difference (P=0.039, 0.002, 0.035). In 103 patients, luminal A, luminal B, HER-2 overexpression and triple negative subtypes in primary lesions and recurrent/metastatic lesions accounted for 8.7% (9/103) and 10.7% (11/103), 54.3% (56/103) and 53.4% (55/103), 18.4% (19/103) and 14.6% (15/103), 18.4% (19/103) and 21.4% (22/103), respectively. After recurrence and metastasis, the proportion of luminal A and triple-negative subtypes increased, and the proportion of other molecular subtypes decreased. Then 6/9, 30.4% (17/56), 7/19, 3/19 of luminal A, luminal B, HER-2 overexpression, and triple-negative subtypes in primary lesions were transformed into other subtypes after recurrence and metastasis.

Conclusions

Gene expression often changes after recurrence and metastasis of breast cancer, and the molecular subtype transformation is common. Through the molecular expression and molecular subtype of recurrent and metastatic lesions, we can develop more accurate treatment schemes to improve the therapeutic effect.

Key words: Breast neoplasms, Neoplasm recurrence, local, Neoplasm metastasis, Gene expression
表1 103例新疆乳腺癌原发灶与复发、转移灶中ER、PR、HER-2、Ki67及p53的表达差异(例)
原发灶 复发、转移灶
ER PR HER-2 Ki67 p53
阳性 阴性 阳性 阴性 阳性 阴性 高 低 阳性 阴性
阳性 57 8 42 15 28 4 56 15 68 3
阴性 1 37 2 44 3 68 15 17 12 20
P值a 0.039 0.002 1.000 1.000 0.035
图1 乳腺癌肺转移灶中雌激素受体的免疫组织化学染色(SP ×200)
图2 乳腺癌肺转移灶中孕激素受体的免疫组织化学染色(SP ×200)
图3 乳腺癌胸壁复发灶中p53的免疫组织化学染色(SP ×200)
图4 乳腺癌肝脏转移灶组织中人表皮生长因子受体2的免疫组织化学染色(SP ×200)
图5 乳腺癌肺转移灶中HER-2的荧光原位杂交图(×200)
图6 乳腺癌肝脏转移灶中Ki67的免疫组织化学染色(SP ×200)　a图为Ki67低表达(≤14%)；b图为Ki67高表达(>14%)
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