Cytogenetic alterations and cytokeratin expression patterns in breast cancer: Integrating a new model of breast differentiation into cytogenetic pathways of breast carcinogenesis
Cytogenetic alterations and cytokeratin expression patterns in breast cancer: Integrating a new model of breast differentiation into cytogenetic pathways of breast carcinogenesis
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DOI：
10.1097/01.lab.0000038508.86221.b3
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发表时间：
2002-11-01
影响因子：
5
通讯作者：
Buerger, H
中科院分区：
文献类型：
--
作者：
Korsching, E;Packeisen, J;Buerger, H
引入一个概念，提出多个细胞亚群在正常女性乳腺，包括细胞角蛋白5/6（CK 5/6）阳性祖细胞，提供了一个新的解释存在的高度侵袭性乳腺癌与CK 5/6表达。使用组织微阵列技术，166例乳腺癌病例，所有的特征在于比较基因组杂交，通过免疫组化，使用15种不同的抗体进行了评价（雌激素受体，孕酮受体，p53，Ki-67，c-erbB 2，表皮生长因子受体，细胞周期蛋白A，D1和E，bcl-2，p21，p27，Ck 5/6，Ck 8/18，和平滑肌肌动蛋白）和c-erbB 2的显色原位杂交。应用生物数学聚类分析，以证实一个独立的方法的结果的传统解释。CK 5/6阳性乳腺癌通常雌激素受体和孕激素受体阴性，高度增殖（如Ki 67和细胞周期蛋白A所反映），并与特定的蛋白表达模式相关，如p53和上皮生长因子受体的表达（均与更具侵袭性的肿瘤行为相关），这可以通过生物数学聚类分析进一步证实。与此相反，CK 5/6阴性乳腺癌显示较低的肿瘤增殖率，p21，p27，c-erbB 2和bcl-2的表达增加，和一个显着较低的遗传变异的数量，与16 q的染色体材料的损失作为最常见的遗传变异。我们的数据给出了第一个提示的假设，即不同的细胞亚群在女性乳房引起不同的蛋白质表达和细胞遗传学改变模式，可能与临床行为的乳腺癌亚群。
The introduction of a concept proposing multiple cellular subgroups in the normal female breast, including cytokeratin 5/6 (Ck 5/6)-positive progenitor cells, offers a new explanation for the existence of highly aggressive breast cancers with and without Ck 5/6 expression. Using the tissue microarray technique, 166 breast cancer cases, all characterized by comparative genomic hybridization, were evaluated by immunohistochemistry, using 15 different antibodies (estrogen receptor, progesterone receptor, p53, Ki-67, c-erbB2, epidermal growth factor receptor, cyclins A, D1, and E, bcl-2, p21, p27, Ck 5/6, Ck 8/18, and smooth muscle actin) and chromogenic in situ hybridization for c-erbB2. Biomathematical cluster analysis was applied to confirm the conventional interpretation of the results by an independent approach. Ck 5/6-positive breast carcinomas were in general negative for estrogen receptor and progesterone receptor, were highly proliferating (as reflected by Ki67 and cyclin A), and were associated with specific protein expression patterns, such as expression of p53 and epithelial growth factor receptor (all related to more aggressive tumor behavior), which could further be demonstrated by biomathematical cluster analysis. In contrast Ck 5/6-negative breast carcinomas revealed a lower tumor proliferation rate, an increased expression of p2l, p27, c-erbB2, and bcl-2, and a significantly lower number of genetic alterations, with losses of chromosomal material of 16q as the most common genetic alteration. Our data give the first hints to the hypothesis that different cellular subgroups in the female breast give rise to subgroups of breast carcinomas with differing protein expression and cytogenetic alteration patterns that may be related to clinical behavior.