Breast Center Seefeld and Oncocenter, Zurich, Switzerland.
County Hospital Waid, Zurich, Switzerland.
Breast Cancer Res Treat. 2020 Sep;183(2):311-319. doi: 10.1007/s10549-020-05772-6. Epub 2020 Jul 7.
Human epidermal growth factor-receptor-2 (HER2) is a membrane-tyrosine-kinase that is amplified/overexpressed up to 20% in breast cancer. HER2 positive status is associated with faster disease progression, higher metastatic potential, and shorter disease-free/overall survival and also has emerged as an important therapeutic target in breast cancer. HER2 status can be determined by in-situ-hybridization (ISH) or immunohistochemistry (IHC). Although the concordance rate between ISH and IHC is well-known, the prognostic power of both technologies if tested in parallel on the same tumor has not been studied extensively.
In this study we retrospectively analyzed a large HER2 positive breast cancer cohort tested both with fluorescence labeled ISH (FISH) and IHC in parallel on each case. We stratified HER2 positive results by FISH and IHC with long-term overall survival, 5-year survival and metastases/recurrence rates. Positive HER2 status both FISH and IHC was available in 364 patients.
The number of HER2 FISH-positive and FISH-negative patients was 342 and 22, respectively. The number of HER2 IHC 0/1 + , IHC 2 + , and IHC 3 + patients was 12, 42, and 310, respectively. Among the patients with IHC 3 + status, 288 were FISH-positive and 22 FISH-negative. HER2 status determined by FISH correlated with clinical outcomes (overall survival and with metastases/recurrence, p = 0.036, p = 0.039), whereas HER2 status determined by IHC did not.
Our results indicate that prognostic information in HER2 positive breast cancer also depends on the methodology of how positivity was determined. In our cohort, FISH was superior to IHC based positive HER2 status.
人表皮生长因子受体-2（HER2）是一种膜酪氨酸激酶，在乳腺癌中扩增/过表达高达 20%。HER2 阳性状态与疾病进展更快、转移潜能更高、无病/总生存期更短有关，并且已成为乳腺癌的重要治疗靶点。HER2 状态可通过原位杂交（ISH）或免疫组织化学（IHC）来确定。虽然 ISH 和 IHC 之间的一致性率是众所周知的，但如果在同一肿瘤上并行测试这两种技术的预后能力尚未得到广泛研究。
在这项研究中，我们回顾性分析了一个大型的 HER2 阳性乳腺癌队列，该队列在每个病例中均同时进行荧光标记 ISH（FISH）和 IHC 检测。我们根据 FISH 和 IHC 将 HER2 阳性结果进行分层，并比较了长期总生存率、5 年生存率和转移/复发率。364 例患者均有 FISH 和 IHC 阳性 HER2 状态。
HER2 FISH 阳性和 FISH 阴性患者的数量分别为 342 例和 22 例。HER2 IHC 0/1+、IHC 2+和 IHC 3+患者的数量分别为 12 例、42 例和 310 例。在 IHC 3+状态的患者中，288 例为 FISH 阳性，22 例为 FISH 阴性。FISH 确定的 HER2 状态与临床结局（总生存率和转移/复发率，p=0.036，p=0.039）相关，而 IHC 确定的 HER2 状态则不然。
我们的结果表明，HER2 阳性乳腺癌的预后信息也取决于确定阳性的方法。在我们的队列中，FISH 优于基于 IHC 的阳性 HER2 状态。
