Internodal HER2 heterogeneity of axillary lymph node metastases in breast cancer patients
Internodal HER2 heterogeneity of axillary lymph node metastases in breast cancer patients
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DOI：
10.17305/bjbms.2019.3970
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发表时间：
2019-01-01
影响因子：
3.4
通讯作者：
Tot, Tibor
中科院分区：
文献类型：
--
作者：
Baros, Ilija Vladimir;Tanaskovic, Natsa;Tot, Tibor
人表皮生长因子受体2（HER 2）状态的测定对于乳腺癌（BC）患者的充分治疗非常重要。新的HER 2基因蛋白测定（GPA）特别方便，因为它允许在单个细胞水平上同时评估HER 2蛋白表达和基因扩增。在这里，我们调查了乳腺癌患者腋窝淋巴结大转移中结间HER 2异质性的频率，并比较了原发性乳腺肿瘤及其转移瘤之间的HER 2状态。我们纳入了2014年至2015年间因原发性BC伴腋窝淋巴结大转移而接受手术的共41例女性患者。在38例BC病例中，对转移性淋巴结的代表性石蜡块进行切片，并使用GPA对载玻片进行染色。GPA结果根据ASCO/CAP 2013标准进行评估。我们分析了12586个个体肿瘤细胞，每个转移性淋巴结的每个切片120个细胞。在5/38例（13.2%）病例中，原发性肿瘤与其转移瘤之间的HER 2状态不同。在至少有两个转移淋巴结的患者中，淋巴结转移的HER 2状态仅在4/23例（17.4%）中略有不同。我们的研究结果表明，原发性乳腺肿瘤和腋窝淋巴结转移瘤之间的HER 2状态存在罕见但实质性的差异，这可能会指导BC患者靶向治疗的选择和结果。本研究中证实的罕见和微妙的结间HER 2异质性的影响仍不确定。确定BC中淋巴结转移的HER 2状态似乎是合理的，但评估有限数量的转移性淋巴结可能就足够了。
Determination of human epidermal growth factor receptor 2 (HER2) status is important for adequate treatment of breast cancer (BC) patients. The novel HER2 gene protein assay (GPA) is particularly convenient, as it allows the simultaneous assessment of HER2 protein expression and gene amplification at individual cell level. Here we investigated the frequency of internodal HER2 heterogeneity in axillary lymph node macrometastases of BC patients and compared HER2 status between primary breast tumor and its metastases. We included a total of 41 female patients operated between 2014 and 2015 for primary BC with axillary lymph node macrometastases. Representative paraffin blocks of metastatic lymph nodes were sectioned and the slides were stained using the GPA in 38 BC cases. GPA results were assessed according to the ASCO/CAP 2013 criteria. We analyzed 12586 individual tumor cells, 120 cells per section of each metastatic lymph node. HER2 status differed between the primary tumor and its metastases in 5/38 cases (13.2%). In patients with at least two metastatic nodes, the HER2 status of lymph node metastases was only slightly different in 4/23 cases (17.4%). Our results indicate rare but substantial differences in HER2 status between primary breast tumor and its axillary lymph node metastases that may direct the choice and outcomes of targeted therapy in BC patients. The impact of the rare and subtle internodal HER2 heterogeneity evidenced in this study remains uncertain. Determining the HER2 status of lymph node metastases in BC seems to be rational, but assessing a limited number of metastatic nodes may be sufficient.