具有基底样特征的三阴性乳腺癌中 EGFR 和 EGFR 下游通路的分子特征。

Molecular characterization of EGFR and EGFR-downstream pathways in triple negative breast carcinomas with basal like features.

机构信息

Institute of Pathology, Locarno, Switzerland.

出版信息

Histol Histopathol. 2012 Jun;27(6):785-92. doi: 10.14670/HH-27.785.

DOI:10.14670/HH-27.785

PMID:22473698

Abstract

AIMS

Triple negative breast cancer with basal like features (TN-BCBL) do not benefit from hormonal and anti-HER2 therapies. As a considerable fraction of TN-BCBLs shows EGFR deregulation, EGFR-targeted therapies have been proposed as an option. The characterization of EGFR and EGFR-downstream members may therefore provide important predictive information.

METHODS AND RESULTS

Based on morphological and immunophenotypic features, we identified 38 TN-BCBLs that were subsequently investigated for alterations in EGFR signaling pathways. EGFR and PTEN protein levels were studied by immunohistochemistry, EGFR gene status by FISH, EGFR, H-Ras, K-Ras, N-Ras, BRAF and PIK3CA gene mutations by direct sequencing. EGFR overexpression and loss of PTEN expression characterized the majority of TN-BCBLs (76% and 74% of patients, respectively). EGFR gene copy number gain (FISH+) was identified in 51% of analyzable patients. PIK3CA gene mutations were detected in three cases (8%), whereas EGFR, H-Ras, K-Ras, N-Ras and BRAF genes showed no mutations. Overall, out of 17 patients classified as FISH+, 12 cases (70%) showed a concomitant alteration in PI3K/PTEN pathway.

CONCLUSIONS

These results provide evidence that the efficacy of anti-EGFR drugs in TN-BCBL patients could be impaired by frequent alterations in the PI3K/PTEN axis, and suggest that TN-BCBLs could benefit from tailored treatments against this axis.

摘要

目的

具有基底样特征的三阴性乳腺癌（TN-BCBL）不能从激素和抗 HER2 治疗中获益。由于相当一部分 TN-BCBL 存在 EGFR 失调，因此提出了 EGFR 靶向治疗作为一种选择。因此，EGFR 和 EGFR 下游成员的特征可能提供重要的预测信息。

方法和结果

基于形态学和免疫表型特征，我们鉴定了 38 例 TN-BCBL，随后对 EGFR 信号通路的改变进行了研究。通过免疫组织化学研究 EGFR 和 PTEN 蛋白水平，通过 FISH 研究 EGFR 基因状态，通过直接测序研究 EGFR、H-Ras、K-Ras、N-Ras、BRAF 和 PIK3CA 基因突变。EGFR 过表达和 PTEN 表达缺失特征是大多数 TN-BCBL 的特征（分别为 76%和 74%的患者）。在可分析的患者中，有 51%的患者 EGFR 基因拷贝数增加（FISH+）。在 3 例（8%）中检测到 PIK3CA 基因突变，而 EGFR、H-Ras、K-Ras、N-Ras 和 BRAF 基因未发生突变。总的来说，在被归类为 FISH+的 17 名患者中，有 12 例（70%）同时存在 PI3K/PTEN 通路改变。