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乳腺大汗腺癌中 X 染色体三体和雄激素受体基因拷贝数异常。

Chromosome X aneusomy and androgen receptor gene copy number aberrations in apocrine carcinoma of the breast.

机构信息

Anatomic Pathology Section, Department of Oncology, Bellaria Hospital, AUSL Bologna, Via Altura 3, 40139, Bologna, Italy.

Pathology Unit, Morgagni-Pierantoni Hospital, Forlì, Italy.

出版信息

Virchows Arch. 2021 Aug;479(2):345-354. doi: 10.1007/s00428-021-03028-2. Epub 2021 Feb 3.

DOI:10.1007/s00428-021-03028-2
PMID:33534004
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC8364532/
Abstract

Carcinomas with apocrine differentiation (CAD) of the breast are rare tumours typically presenting high immunohistochemical expression of androgen receptor (AR) which is a target molecule for personalised therapy. To date, no studies have evaluated the genetic changes that are associated with AR immunohistochemical expression in CADs. The present work aims to characterise AR status in CADs. Twenty CAD tumours were studied with immunohistochemistry, in situ fluorescence hybridization and DNA methylation analysis, to evaluate AR expression and its regulator status. All tumours demonstrated high AR immunohistochemical expression, with over 95% of the neoplastic cells showing AR positivity in 19/20 cases. CADs showed AR gene copy loss in a percentage of neoplastic cells ranging from 5 to 84% (mean 48.93%). AR regulator genes, including the MAGE family, UXT and FLNA, presented variable methylation levels, but were mainly hypomethylated and therefore all transcriptionally active. The results of this study indicate that CADs present AR monosomy, paralleled by higher transcriptional activity of the gene with potential to influence response to AR deprivation therapy.

摘要

乳腺具有大汗腺分化（CAD）的癌是罕见的肿瘤，通常表现为雄激素受体（AR）的高免疫组织化学表达，AR 是个体化治疗的靶分子。迄今为止，尚无研究评估与 CAD 中 AR 免疫组织化学表达相关的遗传变化。本研究旨在研究 CAD 中 AR 的状态。用免疫组织化学、原位荧光杂交和 DNA 甲基化分析研究了 20 例 CAD 肿瘤，以评估 AR 表达及其调节因子的状态。所有肿瘤均表现出高 AR 免疫组织化学表达，在 19/20 例中超过 95%的肿瘤细胞呈 AR 阳性。CAD 中 AR 基因拷贝丢失的肿瘤细胞百分比为 5%至 84%（平均值为 48.93%）。AR 调节基因，包括 MAGE 家族、UXT 和 FLNA，呈现出不同的甲基化水平，但主要是低甲基化，因此均转录活跃。这项研究的结果表明，CAD 存在 AR 单体性，与基因的转录活性更高相关，这可能影响 AR 剥夺治疗的反应。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/705b/8364532/1a8ce131a535/428_2021_3028_Fig9_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/705b/8364532/61cc10c692c5/428_2021_3028_Fig1_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/705b/8364532/d035ee03dc53/428_2021_3028_Fig2_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/705b/8364532/636d9505d375/428_2021_3028_Fig3_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/705b/8364532/0da2739633d0/428_2021_3028_Fig4_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/705b/8364532/b808ccd363df/428_2021_3028_Fig5_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/705b/8364532/483b5d53160f/428_2021_3028_Fig6_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/705b/8364532/2f64485be773/428_2021_3028_Fig7_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/705b/8364532/d394e9131c1c/428_2021_3028_Fig8_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/705b/8364532/1a8ce131a535/428_2021_3028_Fig9_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/705b/8364532/61cc10c692c5/428_2021_3028_Fig1_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/705b/8364532/d035ee03dc53/428_2021_3028_Fig2_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/705b/8364532/636d9505d375/428_2021_3028_Fig3_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/705b/8364532/0da2739633d0/428_2021_3028_Fig4_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/705b/8364532/b808ccd363df/428_2021_3028_Fig5_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/705b/8364532/483b5d53160f/428_2021_3028_Fig6_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/705b/8364532/2f64485be773/428_2021_3028_Fig7_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/705b/8364532/d394e9131c1c/428_2021_3028_Fig8_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/705b/8364532/1a8ce131a535/428_2021_3028_Fig9_HTML.jpg

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