Receptor conversion in distant breast cancer metastases.

Receptor conversion in distant breast cancer metastases.
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DOI:
10.1186/bcr2645
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发表时间:
2010
期刊:
Breast cancer research : BCR
影响因子:
--
通讯作者:
van Diest PJ
van Diest PJ
中科院分区:
其他
文献类型:
--
作者:
Hoefnagel LD;van de Vijver MJ;van Slooten HJ;Wesseling P;Wesseling J;Westenend PJ;Bart J;Seldenrijk CA;Nagtegaal ID;Oudejans J;van der Valk P;van der Groep P;de Vries EG;van der Wall E;van Diest PJ

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当乳腺癌患者发生远处转移时,系统治疗的选择通常基于免疫组织化学(IHC)和/或分子分析确定的原发肿瘤的组织特征。先前的一些研究表明,远处乳腺癌转移的免疫表型可能与原发肿瘤不同(受体转换),导致全身治疗的选择不恰当。然而,到目前为止发表的研究规模都很小,而且/或者在方法上不够理想。因此,尚未得出可能改变临床实践的明确结论。因此,我们的目的是研究雌激素受体α (ERα)、孕激素受体(PR)和人表皮生长因子受体2 (HER2)在一大组远端(非骨)乳腺癌转移中的受体转换,方法是用目前最优的免疫组织化学和原位杂交方法对所有原发肿瘤和转移瘤进行全切片重新染色。对233例不同部位(皮肤76例、肝脏63例、肺43例、脑44例、胃肠道7例)远处转移的乳腺癌患者进行ERα、PR和HER2免疫组化染色,并与原发肿瘤进行比较。在IHC转化或原发肿瘤或转移灶显示IHC 2+结果的情况下,进行HER2原位杂交(ISH)。使用10%的阈值,IHC对ERα和PR的受体转化分别发生在10.3%和30.0%的患者中。10.7%的患者从ER+或PR+转化为ER-/PR-, 3.4%的患者从ER-/PR-转化为ER+或PR+。使用1%的阈值,ERα和PR转化率分别为15.1%和32.6%。12.4%的患者从ER+或PR+转变为ER-/PR-, 8.2%的患者从ER-/PR-转变为ER+或PR+。HER2转化率为5.2%。12例经免疫组化转化为HER2的病例中,5例经ISH转化为HER2。另一个病例显示了ISH的转化,而不是IHC。ERα和PR在原发肿瘤中主要由阳性转化为阴性,而HER2在转移瘤中同样发生转化。PR转化在肝、脑和胃肠道转移中更为常见。在(非骨)远处乳腺癌转移中确实会发生受体转化,但在ERα和HER2中相对少见,而在PR中更为常见,特别是在脑、肝和胃肠道转移中。
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. A total of 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 is more frequent for PR, especially in brain, liver and gastro-intestinal metastases.
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