MUC1 is a transmembrane molecule characterized by a repeated sequence of 20
amino acid (TAP PAHGVTSAPDTRPAPGS). Abnormal overexpression of MUC1 in
cancer cells is thought to contribute to their aggressive growth, but molecular mechanisms associated with this effect are still unclear. Our current study aimed to clarify whether MUC1 expression as recognized by VU-3C6 anti-MUC1 mouse
IgG monoclonal antibody (MAb) with a dominant
epitope of 12
amino acids: GVTSAPDTRPAP, correlated with aggressive properties of human
breast cancer. Immunohistochemical studies of 309 samples of
formalin-fixed and
paraffin-embedded materials showed no statistical correlation between MUC1 expression and clinicopathological parameters, as well as several
breast cancer aggressiveness-related markers. Expression or nonexpression of MUC1 in 50 frozen samples, as determined by Western blotting, demonstrated no correlation with aggressive properties of
breast cancer. However, samples with one MUC1-positive band more often had lymphatic vessel invasion and
lymph node metastasis than those with more than two or three MUC1-positive bands (p<0.014 and p<0.043, respectively). Because VU-3C6 MAb recognizes MUC1 with short branches of O-glycosylated core
carbohydrates, we used immunohistological methods to examine
Tn antigen (precursor
antigen: GalNAcalpha-O-Ser/Thr), Thomsen-Friedenreich (
T) antigen, and
sialyl-Tn antigen (STn)
antigen. We found a strong correlation between expression of MUC1 and
Tn antigen (p<0.0006), and samples with
Tn antigen expression had more
lymphatic metastasis than those with no such expression (p<0.08). We concluded that the lack of polymorphic MUC1 expression with
Tn antigen is one characteristic related to aggressive
breast cancer.