Protein expression analysis of ALCAM and CEACAM6 in breast cancer metastases reveals significantly increased ALCAM expression in metastases of the skin.
OBJECTIVE
For prediction and understanding of underlying mechanisms of organ-specific metastases, various gene and protein expression signatures have been identified in primary breast carcinomas. These expression signatures often include several genes coding for adhesion molecules, such as activated leucocyte cell adhesion molecule (ALCAM/CD166) and carcinoembryonic antigen-related cell adhesion molecule 6 (CEACAM6), both of which may play an important role in the development of distant metastases because of their adherent properties. Owing to their predominantly membranous localisation, they are also considered to have certain therapeutic potential. Apart from expression data obtained in the primary tumour, data for gene and protein expression patterns in distant breast cancer metastases are rare. Therefore this study focuses on analysing the distribution of ALCAM and CEACAM6 protein expression in breast cancer metastases from different sites.


METHODS
Immunohistochemical staining for ALCAM and CEACAM6 in 117 breast cancer metastases derived from liver (n=24), lung (n=19), brain (n=21), bone (n=36) and skin (n=17) was performed.


RESULTS
Immunoreactive scores (IRS) for ALCAM in all metastases except skin metastases ranged from 2.63 to 5.10 (membranous) and 2.79 to 3.67 (cytoplasmic), showing a positive correlation with each other (r=0.690, p<0.001). In skin metastases, ALCAM expression was significantly stronger (membranous IRS, 8.76; cytoplasmic IRS, 7.12; p<0.001). Mean staining intensity for CEACAM6 was IRS 3.88. No or weak CEACAM6 and ALCAM staining (IRS 0-3) was seen in 53% vs 27% of all metastases.


CONCLUSIONS
Compared with CEACAM6, ALCAM showed significantly stronger protein expression in breast cancer skin metastases compared with metastases in all other sites.
Department of Gynaecology, University Medical Center Hamburg-Eppendorf, Hamburg, Germany. maihnen@gmx.ch
Maike
M
Ihnen
Ergin
E
Kilic
Nadine
N
Köhler
Thomas
T
Löning
Isabell
I
Witzel
Christian
C
Hagel
Sylvia
S
Höller
Jan F
JF
Kersten
Volkmar
V
Müller
Fritz
F
Jänicke
Karin
K
Milde-Langosch
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D015703:Antigens, CD / Q000378:metabolism*; D001859:Bone Neoplasms / Q000378:metabolism / Q000556:secondary; D001932:Brain Neoplasms / Q000378:metabolism / Q000556:secondary; D001943:Breast Neoplasms / Q000378:metabolism*; D015815:Cell Adhesion Molecules / Q000378:metabolism*; D015816:Cell Adhesion Molecules, Neuronal / Q000378:metabolism*; D005260:Female; D005326:Fetal Proteins / Q000378:metabolism*; D058851:GPI-Linked Proteins / Q000378:metabolism; D006801:Humans; D008113:Liver Neoplasms / Q000378:metabolism / Q000556:secondary; D008175:Lung Neoplasms / Q000378:metabolism / Q000556:secondary; D008875:Middle Aged; D009363:Neoplasm Proteins / Q000378:metabolism*; D012878:Skin Neoplasms / Q000378:metabolism / Q000556:secondary*; D020410:Activated-Leukocyte Cell Adhesion Molecule
D015703:Antigens, CD; D015815:Cell Adhesion Molecules; D015816:Cell Adhesion Molecules, Neuronal; D005326:Fetal Proteins; D058851:GPI-Linked Proteins; D009363:Neoplasm Proteins; C105613:ALCAM protein, human; D020410:Activated-Leukocyte Cell Adhesion Molecule; C504117:CEACAM6 protein, human