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Loss of ALX4 expression in epithelial cells and adjacent stromal cells in breast cancer
  1. H Chang,
  2. N Mohabir,
  3. S Done,
  4. P A Hamel
  1. Department of Laboratory Medicine & Pathobiology, Faculty of Medicine, University of Toronto, Toronto, Ontario, Canada
  1. Correspondence to Professor P A Hamel, 6318, Medical Science Bldg, 1 King’s College Circle, University of Toronto, Toronto, Ontario M5S 1A8, Canada; paul.hamel{at}


Background: Loss of the stromally-restricted homeodomain transcription factor, Alx4, causes defective mouse mammary epithelial morphogenesis.

Aims: 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.

Methods: Cells expressing ALX4 in the human breast were identified by co-immunofluorescence using α-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.

Results: 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.

Conclusions: 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.

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  • Funding This work was supported through a grant to PAH through a joint programme of the Canadian Breast Cancer Research Alliance, the National Cancer Institute of Canada and the Canadian Institutes of Health Research (MOP-49614).

  • Competing interests None.

  • Ethics approval Ethics approval was obtained.

  • Contributions The first two authors made equivalent contributions to this manuscript. NM was responsible for generation of the data and editing of the manuscript. HC was involved in writing parts of and editing the manuscript as well as preparation of the figures. SD co-directed the project, scored the tissue staining and edited the manuscript. PH is the senior author and was involved in all aspects of this paper.

  • Provenance and peer review Not commissioned; externally peer reviewed.