Department of Pathology, University Medical Center Utrecht, The Netherlands.
Breast Cancer Res. 2010;12(5):R75. doi: 10.1186/bcr2645. Epub 2010 Sep 23.
When breast cancer patients develop distant metastases, the choice of systemic treatment is usually based on tissue characteristics of the primary tumor as determined by immunohistochemistry (IHC) and/or molecular analysis. Several previous studies have shown that the immunophenotype of distant breast cancer metastases may be different from that of the primary tumor ("receptor conversion"), leading to inappropriate choice of systemic treatment. The studies published so far are however small and/or methodologically suboptimal. Therefore, definite conclusions that may change clinical practice could not yet be drawn. We therefore aimed to study receptor conversion for estrogen receptor alpha (ERα), progesterone receptor (PR), and human epidermal growth factor receptor 2 (HER2) in a large group of distant (non-bone) breast cancer metastases by re-staining all primary tumors and metastases with current optimal immunohistochemical and in situ hybridization methods on full sections.
233 distant breast cancer metastases from different sites (76 skin, 63 liver, 43 lung, 44 brain and 7 gastro-intestinal) were IHC stained for ERα, PR and HER2, and expression was compared to that of the primary tumor. HER2 in situ hybridization (ISH) was done in cases of IHC conversion or when primary tumors or metastases showed an IHC 2+ result.
Using a 10% threshold, receptor conversion by IHC for ERα, PR occurred in 10.3%, 30.0% of patients, respectively. In 10.7% of patients, conversion from "ER+ or PR+" to ER-/PR- and in 3.4% from ER-/PR- to "ER+ or PR+" was found. Using a 1% threshold, ERα and PR conversion rates were 15.1% and 32.6%. In 12.4% of patients conversion from "ER+ or PR+" to ER-/PR-, and 8.2% from ER-/PR- to "ER+ or PR+" occurred. HER2 conversion occurred in 5.2%. Of the 12 cases that showed HER2 conversion by IHC, 5 showed also conversion by ISH. One further case showed conversion by ISH, but not by IHC. Conversion was mainly from positive in the primary tumor to negative in the metastases for ERα and PR, while HER2 conversion occurred equally both ways. PR conversion occurred significantly more often in liver, brain and gastro-intestinal metastases.
Receptor conversion by immunohistochemistry in (non-bone) distant breast cancer metastases does occur, is relatively uncommon for ERα and HER2, and more frequent for PR, especially in brain, liver and gastro-intestinal metastases.
当乳腺癌患者出现远处转移时，全身治疗的选择通常基于原发性肿瘤的组织特征，这些特征通过免疫组织化学（IHC）和/或分子分析来确定。多项先前的研究表明，远处乳腺癌转移的免疫表型可能与原发性肿瘤不同（“受体转换”），导致全身治疗选择不当。然而，迄今为止发表的研究规模较小，/或方法学上不够完善。因此，还不能得出可能改变临床实践的明确结论。因此，我们旨在通过使用当前最佳的免疫组织化学和原位杂交方法对所有原发性肿瘤和转移灶进行全切片重新染色，在一大组远处（非骨）乳腺癌转移灶中研究雌激素受体 alpha（ERα）、孕激素受体（PR）和人表皮生长因子受体 2（HER2）的受体转换。
对来自不同部位的 233 例远处乳腺癌转移灶（76 例皮肤，63 例肝脏，43 例肺，44 例脑和 7 例胃肠道）进行 ERα、PR 和 HER2 的免疫组织化学染色，并将其表达与原发性肿瘤进行比较。在 IHC 转换的情况下，或在原发性肿瘤或转移灶显示 IHC 2+结果的情况下，进行 HER2 原位杂交（ISH）。
使用 10%的阈值，ERα、PR 的 IHC 受体转换率分别为 10.3%和 30.0%。在 10.7%的患者中，发现从“ER+或 PR+”到 ER-/PR-的转换，以及从 ER-/PR-到“ER+或 PR+”的转换率为 3.4%。使用 1%的阈值，ERα 和 PR 的转换率分别为 15.1%和 32.6%。在 12.4%的患者中，从“ER+或 PR+”到 ER-/PR-的转换，以及从 ER-/PR-到“ER+或 PR+”的转换率为 8.2%。HER2 转换率为 5.2%。在 12 例 HER2 IHC 转换的病例中，5 例通过 ISH 也发生了转换。另有 1 例病例通过 ISH 发生了转换，但通过 IHC 没有发生转换。转换主要从原发性肿瘤中的阳性变为转移灶中的阴性，而 PR 的转换则两种方式均有发生。PR 转换在肝、脑和胃肠道转移灶中更为常见。
（非骨）远处乳腺癌转移灶的免疫组化受体转换确实存在，对于 ERα 和 HER2 来说相对少见，而对于 PR 来说则更为常见，尤其是在脑、肝和胃肠道转移灶中。
