人表皮生长因子受体 2 蛋白在乳腺外派杰病中的过表达和基因扩增。

Human epidermal growth factor receptor 2 protein overexpression and gene amplification in extramammary Paget disease.

机构信息

Department of Dermatologic Oncology, National Cancer Center Hospital, Tokyo, Japan.

出版信息

Br J Dermatol. 2013 Jun;168(6):1259-66. doi: 10.1111/bjd.12249.

DOI:10.1111/bjd.12249

PMID:23360223

Abstract

BACKGROUND

Several recent studies have reported on the overexpression of human epidermal growth factor receptor (HER)2 in extramammary Paget disease (EMPD). However, there are only a few cases in which both overexpression and gene amplification of HER2 have been examined.

OBJECTIVES

To evaluate the overexpression and gene amplification of HER2 using a standardized method with a large number of cases of EMPD.

METHODS

Immunohistochemically, the overexpression of the HER2 protein was examined in 104 cases of EMPD, including 31 intraepithelial cases and 73 invasive cases (35 superficially invasive and 38 deeply invasive). When the HER2 protein was overexpressed or potentially overexpressed, further analysis of amplification of the gene encoding HER2, ERBB2, was undertaken using fluorescence in situ hybridization.

RESULTS

The HER2 protein was overexpressed in 16 cases (15%) in total, and in 13 of 73 cases (18%) of invasive EMPD. The ERBB2 gene was amplified in all cases with a HER2 score of 3+. A HER2 score of 3+ or 2+, and ERBB2 amplification were significantly more frequent in the cases of deeply invasive EMPD than in intraepithelial/superficially invasive EMPD (24% vs. 6%/3%, P=0·012) and were correlated with a larger number of lymph-node metastases (P=0·047). Log-rank tests for survival curves showed that lymph-node metastasis and ERBB2 amplification were significant prognostic factors (P=0·0001 and P=0·043, respectively). However, by a multivariate analysis, only lymph-node status was a significant indicator of Paget-disease-specific survival (P=0·0001).

CONCLUSIONS

A subset of EMPD, both intraepithelial and invasive, showed HER2 overexpression and gene amplification. These HER2 alterations were correlated with biologically aggressive EMPDs, i.e. those with deep invasion and lymph-node metastasis. Clinical trials of HER2-targeted therapy are awaited for improvement of the prognosis of patients with aggressive EMPD.

摘要

背景

多项近期研究报道了外阴派杰病（EMPD）中存在人表皮生长因子受体（HER）2 的过表达。然而，仅有少数病例同时检测到 HER2 的过表达和基因扩增。

目的

使用标准化方法评估大量 EMPD 病例中 HER2 的过表达和基因扩增。

方法

通过免疫组化检测了 104 例 EMPD 中 HER2 蛋白的过表达情况，包括 31 例上皮内病例和 73 例浸润性病例（35 例浅层浸润和 38 例深层浸润）。当 HER2 蛋白过表达或可能过表达时，使用荧光原位杂交进一步分析编码 HER2 的基因 ERBB2 的扩增情况。

结果

总共 16 例（15%）病例 HER2 蛋白过表达，73 例浸润性 EMPD 病例中有 13 例（18%）过表达。HER2 评分 3+的所有病例均扩增 ERBB2 基因。HER2 评分 3+或 2+且 ERBB2 扩增在深层浸润性 EMPD 病例中更为常见（24%比上皮内/浅层浸润性 EMPD 病例中的 6%/3%，P=0·012），且与更多的淋巴结转移相关（P=0·047）。生存曲线的对数秩检验显示，淋巴结转移和 ERBB2 扩增是显著的预后因素（P=0·0001 和 P=0·043）。然而，通过多变量分析，仅淋巴结状态是 EMPD 特异性生存的显著指标（P=0·0001）。