Expression of sialyl lewis X, sialyl Lewis A, E-cadherin and cathepsin-D in human breast cancer: immunohistochemical analysis in mammary carcinoma in situ, invasive carcinomas and their lymph node metastasis.
OBJECTIVE
Breast cancer cells can invade and generate metastasis via either lymphatic or blood vessels. Sialyl Lewis X (SLeX) and Sialyl Lewis a (SLea) are carbohydrate molecules that mediate the adhesion between tumor cells and the endothelium. These antigens are not expressed on normal breast tissue. Overexpression of SLeX and SLea is combined with poor prognosis and malignant relapse. E-cadherin mediates tumor cell-tumor cell adhesion. Partial or complete loss of E-cadherin expression has also been found to correlate with poor prognosis in breast cancer patients. Another factor involved in metastasis is Cathepsin-D, a lysosomalprotease. Cathepsin-D plays a role in cell proliferation and inhibition of tumor cell adhesion. In this study, we analysed the combined expression of SLeX, SLea, Cathepsin-D and E-cadherin in breast carcinoma in situ, invasive carcinomas without metastasis and invasive carcinomas with lymph node metastasis.


METHODS
Slides of paraffin-embedded tissue of carcinoma in situ (8 DCIS, 2 CLIS), invasive carcinomas without metastasis (9 ductal, 1 lobular) and carcinomas (7 ductal, 2 lobular, 1 mucinous) with their lymph node metastasis (10 cases) were used. Breast cancer tissue was fixed and incubated with monoclonal antibodies against SLex (IgM) and SLea (IgM), Cathepsin-D (IgG) and E-cadherin (IgG). Staining reaction was performed with the ABC reagent. The intensity of immunohistochemical reaction on digital images of the slides was analyzed using a computer-aided detection system.


RESULTS
We found a weak expression of both Sialyl Lewis antigens, a strong expression of E-cadherin and a moderate expression of Cathepsin-D in carcinoma in situ. The expression of both Sialyl Lewis antigens, E-cadherin and Cathepsin-D was moderate in invasive carcinomas without metastases. However, a strong expression of both Sialyl Lewis antigens and a very weak expression of E-cadherin was detected in primary carcinoma with lymph node metastases. The expression of Cathepsin-D was moderate in this tissue. E-cadherin expression was elevated whereas SLeX and Cathepsin-D expression was reduced in lymph node metastases compared to the primary tumor.


CONCLUSIONS
Combined analysis of tumor antigens involved in adhesion of breast cancer cells showed a negative correlation between Sialyl Lewis antigens and E-cadherin as the risk of metastasis progresses. Furthermore, there were significant differences of expression of the Sialyl Lewis antigens, E-cadherin and Cathepsin-D in primary breast cancer cells and their metastases. Evaluation of a panel of markers involved in cell adhesion could be a useful method for defining the metastatic risk in breast cancer patients.
Jeschke
Udo
U
I Department of Obstetrics and Gynecology, Ludwig-Maximilians-University of Munich, Munich, Germany. udo.jeschke@fk-i.med.uni-muenchen.de
Mylonas
Ioannis
I
Shabani
Naim
N
Kunert-Keil
Christiane
C
Schindlbeck
Christian
C
Gerber
Bernd
B
Friese
Klaus
K
D001943:Breast Neoplasms / Q000378:metabolism* / Q000473:pathology; D018395:CA-19-9 Antigen; D015820:Cadherins / Q000378:metabolism*; D002278:Carcinoma in Situ / Q000378:metabolism* / Q000473:pathology; D002402:Cathepsin D / Q000378:metabolism*; D005732:Gangliosides / Q000378:metabolism*; D006801:Humans; D007150:Immunohistochemistry; D008207:Lymphatic Metastasis; D009361:Neoplasm Invasiveness; D009844:Oligosaccharides / Q000378:metabolism*; D000080506:Sialyl Lewis X Antigen
D018395:CA-19-9 Antigen; D015820:Cadherins; D005732:Gangliosides; D009844:Oligosaccharides; D000080506:Sialyl Lewis X Antigen; C064564:sialyl Le(a) ganglioside; D002402:Cathepsin D