Lambein Kathleen, Van Bockstal Mieke, Vandemaele Lies, Van den Broecke Rudy, Cocquyt Veronique, Geenen Sofie, Denys Hannelore, Libbrecht Louis
Department of Pathology, AZ St Lucas Hospital, Groenebriel 1, 9000, Ghent, Belgium.
Department of Oncology, KU Leuven, Surgical Oncology, University Hospitals Leuven, Herestraat 49, 3000, Leuven, Belgium.
Virchows Arch. 2017 Nov;471(5):575-587. doi: 10.1007/s00428-017-2161-8. Epub 2017 May 31.
Although the prognostic and predictive significance of human epidermal growth factor receptor 2 (HER2) in invasive breast cancer is well established, its role in ductal carcinoma in situ (DCIS) remains unclear. Reports on combined evaluation of both HER2 protein expression and HER2 amplification status in pure DCIS and DCIS adjacent to invasive ductal carcinoma (i.e., admixed DCIS) are scarce. In this study, immunohistochemistry and fluorescence in situ hybridization (FISH) were used to assess HER2 status in 72 cases of pure DCIS, 73 cases of DCIS admixed with invasive ductal carcinoma (IDC), and 60 cases of pure IDC. HER2 copy number-based amplification was present in 49% of pure DCIS, 16% of admixed DCIS, 18% of admixed IDC, and 8% of pure IDC. Amplified pure DCIS with clusters of HER2 signals showed a significantly lower HER2 copy number than amplified admixed DCIS with clusters. Whereas pure DCIS and admixed DCIS presented significant differences, the in situ and invasive component of admixed tumors showed striking similarities regarding mean HER2 and chromosome 17 centromere (CEP17) copy number, grade, and estrogen and progesterone receptor expression. The discrepant prevalence of HER2 amplification among breast cancer subgroups indirectly suggests that HER2 may not play a crucial role in the transition of in situ to invasive breast cancer. The similarities in HER2 amplification status between the in situ and invasive component of admixed tumors hint at a common biological pathway for both components. Our data support the theory that pure DCIS, pure IDC, and admixed lesions have a common progenitor, but can progress as separate lineages.
尽管人表皮生长因子受体2（HER2）在浸润性乳腺癌中的预后和预测意义已得到充分证实，但其在导管原位癌（DCIS）中的作用仍不明确。关于在单纯DCIS以及浸润性导管癌旁的DCIS（即混合性DCIS）中联合评估HER2蛋白表达和HER2扩增状态的报道很少。在本研究中，采用免疫组织化学和荧光原位杂交（FISH）技术评估了72例单纯DCIS、73例合并浸润性导管癌（IDC）的DCIS以及60例单纯IDC的HER2状态。单纯DCIS中49%存在基于HER2拷贝数的扩增，混合性DCIS中为16%，混合性IDC中为18%，单纯IDC中为8%。具有HER2信号簇的扩增型单纯DCIS的HER2拷贝数显著低于具有信号簇的扩增型混合性DCIS。虽然单纯DCIS和混合性DCIS存在显著差异，但混合性肿瘤的原位和浸润成分在平均HER2和17号染色体着丝粒（CEP17）拷贝数、分级以及雌激素和孕激素受体表达方面表现出惊人的相似性。乳腺癌亚组中HER2扩增的不同患病率间接表明，HER2可能在原位乳腺癌向浸润性乳腺癌的转变中不起关键作用。混合性肿瘤原位和浸润成分之间HER2扩增状态的相似性暗示了这两种成分具有共同的生物学途径。我们的数据支持这样一种理论，即单纯DCIS、单纯IDC和混合性病变有一个共同的祖细胞，但可以作为独立的谱系进展。
