Department of Laboratory Medicine & Pathobiology, Faculty of Medicine, University of Toronto, Toronto, Ontario, Canada.
J Clin Pathol. 2009 Oct;62(10):908-14. doi: 10.1136/jcp.2009.067298.
Loss of the stromally-restricted homeodomain transcription factor, Alx4, causes defective mouse mammary epithelial morphogenesis.
To begin to define the role of ALX4 in the human breast and in breast cancer, the expression pattern of ALX4 in the normal human breast and changes in expression in breast cancer were determined.
Cells expressing ALX4 in the human breast were identified by co-immunofluorescence using alpha-ALX4 antibodies and markers of specific mammary cell types. ALX4 expression in breast cancer was then determined by immunohistochemistry on tumour sections that also harboured regions of normal breast tissue. Using criteria that required ALX4 staining in both stromal and epithelial cells, changes in ALX4 expression in tumours on a tissue microarray were determined.
ALX4 was expressed in both stromal and luminal epithelial cells in the human breast. Scoring tissue sections of duct carcinoma in situ (DCIS) or invasive ductal carcinoma (IDC) that also harboured regions of normal breast tissue, a loss of ALX4 (p<0.001) in stromal and epithelial cells in breast tumours was observed. Analysis of ALX4 expression in 123 sections on a tissue microarray confirmed a highly significant loss (p<0.001) of ALX4 in breast cancer in the tumours themselves and in adjacent stromal cells.
These data show a distinct pattern of expression of ALX4 in the human breast relative to the murine mammary gland. Furthermore, characterisation of ALX4 in breast cancer showed that loss of ALX4 in tumours and the surrounding untransformed stroma is a basic characteristic of DCIS and IDC.
基质限制性同源盒转录因子 Alx4 的缺失导致小鼠乳腺上皮形态发生缺陷。
为了开始确定 ALX4 在人类乳房和乳腺癌中的作用，本研究确定了 ALX4 在正常人类乳房中的表达模式以及在乳腺癌中的表达变化。
通过使用 α-ALX4 抗体和特定乳腺细胞类型的标志物进行共免疫荧光，鉴定出在人类乳房中表达 ALX4 的细胞。然后通过免疫组织化学在肿瘤切片上检测 ALX4 的表达，这些切片还包含正常乳腺组织的区域。使用需要 ALX4 在基质和上皮细胞中均染色的标准，确定组织微阵列上肿瘤中 ALX4 表达的变化。
ALX4 在人类乳房的基质和腔上皮细胞中均有表达。对同时包含正常乳腺组织区域的导管原位癌 (DCIS) 或浸润性导管癌 (IDC) 的组织切片进行评分，观察到乳腺癌中 ALX4 在基质和上皮细胞中的丢失 (p<0.001)。在组织微阵列上对 123 个切片进行 ALX4 表达分析证实，乳腺癌中肿瘤本身和相邻基质细胞中 ALX4 的丢失具有高度显著性 (p<0.001)。
这些数据显示了 ALX4 在人类乳房中的表达模式与小鼠乳腺有明显不同。此外，对乳腺癌中 ALX4 的特征分析表明，肿瘤和周围未转化的基质中 ALX4 的缺失是 DCIS 和 IDC 的基本特征。
