Tapia Coya, Savic Spasenija, Wagner Urs, Schönegg René, Novotny Hedvika, Grilli Bruno, Herzog Michelle, Barascud Audrey Devito, Zlobec Inti, Cathomas Gieri, Terracciano Luigi, Feichter Georg, Bubendorf Lukas
University Department of Pathology of Basel and Baselland, Institute for Pathology, Schönbeinstrasse 40, Basel, 4003, Switzerland.
Breast Cancer Res. 2007;9(3):R31. doi: 10.1186/bcr1676.
The status of the gene encoding human EGF-like receptor 2 (HER2) is an important prognostic and predictive marker in breast cancer. Only breast cancers with HER2 amplification respond to the targeted therapy with trastuzumab. It is controversial to what degree the primary tumour is representative of distant metastases in terms of HER2 status. Discrepancies in HER2 status between primary tumours and distant metastases have been described, but their reasons remain unclear. Here, we compared HER2 status on cytological specimens of distant metastases with the result from the primary carcinomas, and explored the prevalence of and the reasons for discrepant results.
HER2 status was determined by fluorescence in situ hybridisation. HER2 gene amplification was defined as a HER2/chromosome 17 signal ratio of 2 or more. HER2 results from cytological specimens of matched distant metastases were compared with the results from the corresponding primary tumours (n = 105 patients). In addition, lymph node metastases were analysed in 31 of these patients.
HER2 amplification was found in 20% of distant metastases. HER2 status was discordant between the primary tumour and distant metastasis in 7.6% of the 105 patients. Re-evaluation revealed that in five patients (4.7%), discrepancies were due to interpretational difficulties. In two of these patients, focal amplification had initially been overlooked as a result of heterogeneity in the primary tumours or in the metastases, respectively. A further three patients had borderline amplification with a ratio close to 2. Discrepancy remained unexplained in three patients (2.9%).
HER2 gene status remains highly conserved as breast cancers metastasise. However, discrepant results do occur because of interpretational difficulties and heterogeneity of HER2 amplification. Cytological specimens from distant metastases are well suited for HER2 fluorescence in situ hybridisation analysis.
人类表皮生长因子样受体2（HER2）基因状态是乳腺癌重要的预后和预测标志物。只有HER2基因扩增的乳腺癌对曲妥珠单抗靶向治疗有反应。就HER2状态而言，原发性肿瘤在多大程度上代表远处转移存在争议。原发性肿瘤和远处转移灶之间HER2状态的差异已有报道，但其原因尚不清楚。在此，我们比较了远处转移灶细胞学标本的HER2状态与原发性癌的检测结果，并探讨了结果不一致的发生率及原因。
采用荧光原位杂交法检测HER2状态。HER2基因扩增定义为HER2/17号染色体信号比≥2。将配对的远处转移灶细胞学标本的HER2检测结果与相应原发性肿瘤（n = 105例患者）的结果进行比较。此外，对其中31例患者的淋巴结转移情况进行了分析。
20%的远处转移灶发现有HER2基因扩增。105例患者中，7.6%的原发性肿瘤和远处转移灶的HER2状态不一致。重新评估显示，5例患者（4.
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