Loss of ALX4 expression in epithelial cells and adjacent stromal cells in breast cancer.
BACKGROUND
Loss of the stromally-restricted homeodomain transcription factor, Alx4, causes defective mouse mammary epithelial morphogenesis.


OBJECTIVE
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 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.


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.
Department of Laboratory Medicine & Pathobiology, Faculty of Medicine, University of Toronto, Toronto, Ontario, Canada.
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H
Chang
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N
Mohabir
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Done
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PA
Hamel
D000818:Animals; D001940:Breast / Q000166:cytology / Q000378:metabolism*; D001943:Breast Neoplasms / Q000378:metabolism* / Q000473:pathology; D018270:Carcinoma, Ductal, Breast / Q000378:metabolism / Q000473:pathology; D002285:Carcinoma, Intraductal, Noninfiltrating / Q000378:metabolism / Q000473:pathology; D004268:DNA-Binding Proteins / Q000378:metabolism*; D004847:Epithelial Cells / Q000378:metabolism; D005260:Female; D018398:Homeodomain Proteins / Q000378:metabolism; D006801:Humans; D008321:Mammary Glands, Animal / Q000166:cytology / Q000378:metabolism; D051379:Mice; D008810:Mice, Inbred C57BL; D009363:Neoplasm Proteins / Q000378:metabolism; D013045:Species Specificity; D017154:Stromal Cells / Q000378:metabolism; D046888:Tissue Array Analysis / Q000379:methods; D014157:Transcription Factors / Q000378:metabolism*
C416676:ALX4 protein, human; C109218:Alx4 protein, mouse; D004268:DNA-Binding Proteins; D018398:Homeodomain Proteins; D009363:Neoplasm Proteins; D014157:Transcription Factors