Department of Histopathology, St Bartholomew's Hospital, West Smithfield, London, UK.
Ann Diagn Pathol. 2010 Feb;14(1):1-7. doi: 10.1016/j.anndiagpath.2009.05.001.
Apocrine metaplasia (APM) is a common finding in the breast of postmenopausal women and is seen in a broad spectrum of lesions ranging from microscopic cysts to invasive apocrine carcinoma. Apocrine metaplasia within sclerosing adenosis is known as apocrine adenosis (AA) and is considered a benign lesion of the breast. Apocrine metaplasia and AA have been the subject of many studies; however, little is known about the dynamics of cell turnover in these lesions. Recent studies have shown that some forms of AA may show altered degree of proliferation along with altered expression of bcl-2 and bax proteins. In the current study, we investigate further aspects of apoptosis to help understand the mechanisms of cell turnover in AA and APM. To investigate cell turnover in APM and AA, immunohistochemistry was used to study the expression of the apoptotic markers Bak, Mcl-1, Bcl-x, and Bcl-x(L) in 45 cases of APM (13 cases of nonpapillary APM, 21 cases of simple papillary APM, and 11 cases of complex papillary APM). Also, 34 cases of AA (23 cases of non-atypical AA [NAA] and 11 cases of atypical AA [AAA]) were included in the study. The expression of hTERT and the proliferation marker Ki-67 were also determined. The TdT-mediated dUTP nick-end labeling (TUNEL) technique was used to study the apoptotic status in 28 cases of APM (12 cases nonpapillary APM and 16 cases of papillary APM including simple and complex forms) and 22 cases of AA (15 cases of NAA and 7 cases of AAA). The results showed that all cases studied by immunohistochemistry were positive for the expression of Bak, Mcl-1, Bcl-x, and Bcl-x(L) showing a pattern of staining similar to that seen in the normal breast epithelium. There was no relation between hTERT positivity and the degree of proliferation in any of the lesions studied. The TUNEL results revealed an apoptotic index (AI) of 0.4% and 0.2% in the papillary and nonpapillary groups of APM, respectively. There was no statistical significance between the AI of these 2 groups and that of the normal breast epithelium (0.3%). The average Ki-67 index in the nonpapillary group was 0.7%, whereas in the papillary group, a value of 4% was recorded. In the cases of AA, an AI of 0.4% and 0.3% in NAA and AAA, respectively, was seen. There was no statistical significance between the AI of these 2 groups and that of the normal breast epithelium (0.3%). The Ki-67 index was 5.2% and 6.6% in the NAA and AAA, respectively. The current results show that apoptosis is not a common event in APM and AA even in the presence of increased proliferation, which may render some of these lesions more susceptible to oncogenic changes. Further studies are needed to study other apoptotic pathways that may be involved in cell turnover in these lesions.
大汗腺化生(APM)是绝经后妇女乳腺的常见表现,可见于从微观囊肿到浸润性大汗腺癌等广泛病变。在硬化性腺病中的大汗腺化生称为大汗腺性腺病(AA),被认为是乳腺的良性病变。大汗腺化生和 AA 已经成为许多研究的主题;然而,对于这些病变中细胞更新的动力学知之甚少。最近的研究表明,某些形式的 AA 可能表现出增殖程度的改变,同时 bcl-2 和 bax 蛋白的表达也发生改变。在本研究中,我们进一步研究细胞凋亡的各个方面,以帮助了解 AA 和 APM 中细胞更新的机制。为了研究 APM 和 AA 中的细胞更新,我们使用免疫组织化学方法研究了 45 例 APM(13 例非乳头状 APM、21 例单纯乳头状 APM 和 11 例复杂乳头状 APM)中凋亡标志物 Bak、Mcl-1、Bcl-x 和 Bcl-x(L)的表达。还包括 34 例 AA(23 例非典型 AA [NAA]和 11 例典型 AA [AAA])。还确定了 hTERT 和增殖标志物 Ki-67 的表达。TdT 介导的 dUTP 缺口末端标记(TUNEL)技术用于研究 28 例 APM(12 例非乳头状 APM 和 16 例包括单纯和复杂形式的乳头状 APM)和 22 例 AA(15 例 NAA 和 7 例 AAA)中的凋亡状态。结果显示,所有通过免疫组织化学研究的病例均表达 Bak、Mcl-1、Bcl-x 和 Bcl-x(L),其染色模式与正常乳腺上皮相似。在任何研究的病变中,hTERT 阳性与增殖程度之间均无关系。TUNEL 结果显示,APM 的乳头状和非乳头状组的凋亡指数(AI)分别为 0.4%和 0.2%。这两组与正常乳腺上皮(0.3%)的 AI 之间无统计学意义。非乳头状组的平均 Ki-67 指数为 0.7%,而乳头状组记录的数值为 4%。在 AA 中,NAA 和 AAA 的 AI 分别为 0.4%和 0.3%。这两组与正常乳腺上皮(0.3%)的 AI 之间无统计学意义。NAA 和 AAA 的 Ki-67 指数分别为 5.2%和 6.6%。目前的结果表明,即使增殖增加,APM 和 AA 中细胞凋亡也不是常见事件,这可能使这些病变中的某些更易发生致癌变化。需要进一步研究以研究可能参与这些病变中细胞更新的其他凋亡途径。