Prasad Prakruthi, Bennett Aneliese, Speirs Val, Shaaban Abeer M
School of Medicine, University of Sheffield, Sheffield, United Kingdom.
Cellular Pathology, Mid Yorkshire Hospital National Health Service (NHS) Trust, Dewsbury, United Kingdom.
Front Oncol. 2022 Jun 23;12:875839. doi: 10.3389/fonc.2022.875839. eCollection 2022.
Gynaecomastia is the commonest male breast condition accounting for approximately 85% of male breast lesions. There is minimal information on the immunohistochemical profile of gynaecomastia. We aimed to comprehensively profile a large series of gynaecomastia samples for putative mammary diagnostic, predictive and prognostic markers.
A total of 156 samples, were histologically reviewed, assembled onto tissue microarrays, and stained for oestrogen receptors (ERα, ERβ1, ERß2), progesterone receptors (total PR, PRα), androgen receptor (AR), basal & luminal cytokeratins (CK5/6, CK14, CK8/18) and the proliferation marker Ki67. Relevant cut offs for marker positivity were defined based on existing literature: AR (10%), ERα and PR (Allred score >3/8), ERß (10% and 20%), cytokeratins (10%) and Ki67 (10% and 20%).
108 samples from 86 patients aged 13-75 years were available for immunohistochemical assessment. 73.1% of the lesions were AR positive, compared to 99% for ERα and 100% for both ERß1 and ERß2. 98% of samples were positive for total PR and 97.1% for PRα. 69.8% expressed CK5/6 whilst 57% were CK14 positive. A tri-layered pattern of cytokeratin expression was also observed. Ki67 positivity was low with 17.1% and 6.7% classified as Ki67 positive using 10% and 20% cut off values respectively. A significant negative correlation was found between ERα expression and patient age (rs = -0.221, p=0.023). Bivariate correlations were produced, and comparisons made with previously published data regarding the immunohistochemical status in normal female breast tissue, proliferative and neoplastic breast diseases of the female and male breast.
Hormone receptors, including oestrogen receptor α and ß isoforms as well as androgen receptors were abundantly expressed within the intraductal luminal hyperplastic epithelium in gynaecomastia supporting the hormonal role in the pathogenesis and treatment. ERα, ERβ1 and ERβ2 were expressed in a higher proportion of cells compared with their expression in the female breast benign lesions which further characterises gynaecomastia biology. The identification of a low Ki67 proliferative index and the mixed cytokeratin profile in gynaecomastia differentiates this benign condition from male breast cancer. Therefore, Ki67 and cytokeratins can help in the differential diagnosis from histological mimics in the routine diagnostic work up.
男性乳房肥大是最常见的男性乳房疾病，约占男性乳房病变的85%。关于男性乳房肥大的免疫组化特征的信息极少。我们旨在全面分析大量男性乳房肥大样本，寻找可能的乳腺诊断、预测和预后标志物。
共156个样本经组织学检查后，制作成组织芯片，并进行雌激素受体（ERα、ERβ1、ERβ2）、孕激素受体（总PR、PRα）、雄激素受体（AR）、基底及腔面细胞角蛋白（CK5/6、CK14、CK8/18）和增殖标志物Ki67的染色。根据现有文献确定标志物阳性的相关临界值：AR（10%）、ERα和PR（艾尔雷德评分>3/8）、ERβ（10%和20%）、细胞角蛋白（10%）和Ki67（10%和20%）。
来自86例年龄在13至75岁患者的108个样本可用于免疫组化评估。73.1%的病变AR阳性，而ERα为99%，ERβ1和ERβ2均为100%。98%的样本总PR阳性，97.1%的样本PRα阳性。69.8%表达CK5/6，57%的样本CK14阳性。还观察到细胞角蛋白表达的三层模式。Ki67阳性率较低，分别采用10%和20%的临界值时，17.1%和6.7%的样本被归类为Ki67阳性。发现ERα表达与患者年龄之间存在显著负相关（rs = -0.221，p = 0.023）。进行了双变量相关性分析，并与先前发表的关于正常女性乳腺组织、女性和男性乳腺增生性及肿瘤性疾病免疫组化状态的数据进行了比较。
激素受体，包括雌激素受体α和β异构体以及雄激素受体，在男性乳房肥大的导管内增生性上皮中大量表达，支持其在发病机制和治疗中的激素作用。与在女性乳腺良性病变中的表达相比，ERα、ERβ1和ERβ2在更多比例的细胞中表达，这进一步刻画了男性乳房肥大的生物学特性。男性乳房肥大中Ki67增殖指数低和细胞角蛋白谱混合的特征将这种良性疾病与男性乳腺癌区分开来。因此，Ki67和细胞角蛋白有助于在常规诊断工作中与组织学相似病变进行鉴别诊断。
