Correlation of prognosis of breast cancer patients and expression of Ley which acts as a cofactor of tumor procoagulant.
Association between Ley expression and prognosis of breast cancer was investigated using monoclonal antibody (MoAb) FS01, which recognizes Ley as an epitope, inhibits the procoagulant activity of cancer cell-derived coagulating activity 1 (CCA-1). Expression intensity and procoagulant activity of CCA-1, tissue factor and HLA-DR on breast cancer cell lines were also examined. Immunohistochemical staining of Ley was performed on primary lesions of 223 breast cancer patients who received absolute curative operation. Flow cytometric analysis and clot timer was used to detect expression and activity of each procoagulant on cancer cell lines. The Ley expression was 73.5%, and no significant relation was observed between clinicopathological factors and intensity of Ley expression. The group showing strong Ley positivity had a significantly poorer prognosis than the Ley-negative group in 5-year disease-free survival (p=0.019). Multivariate analysis using the Cox's proportional hazards' regression model showed that Ley expression is an independent prognostic factor (p=0.018), following tumor size and lymph node metastasis. Ley expression on cancer cell surface is higher than tissue factor and HLA-DR. FS01 and anti-tissue factor MoAb inhibited the coagulating activity of tissue factor-expressing lines, but no cells were inhibited by staphylococcal enterotoxin A, which is known to inhibit the coagulating activity of HLA-DR. CCA-1 and tissue factor plays a important role in the blood coagulating activity of breast cancer cell lines. Breast cancer patients are thought to have a poor prognosis because Ley expression on the surface of the cancer cell induces blood coagulation via CCA-1.
The First Department of Surgery, Kinki University School of Medicine, Osaka, 589-8511, Japan.
H
H
Inufusa
Y
Y
Nakatani
T
T
Adachi
T
T
Wakano
A
A
Nakajima
M
M
Nakamura
M
M
Suzuki
O
O
Ando
M
M
Kurimoto
M
M
Miyake
K
K
Shindo
M
M
Yasutomi
D000368:Aged; D000911:Antibodies, Monoclonal / Q000494:pharmacology; D001777:Blood Coagulation / Q000502:physiology; D001779:Blood Coagulation Factors / Q000096:biosynthesis / Q000502:physiology; D001943:Breast Neoplasms / Q000097:blood* / Q000378:metabolism; D004768:Enterotoxins / Q000494:pharmacology; D005260:Female; D006684:HLA-DR Antigens / Q000096:biosynthesis; D006801:Humans; D007150:Immunohistochemistry; D007983:Lewis Blood Group Antigens / Q000096:biosynthesis* / Q000502:physiology; D008875:Middle Aged; D015999:Multivariate Analysis; D011379:Prognosis; D013925:Thromboplastin / Q000276:immunology; D014407:Tumor Cells, Cultured
D000911:Antibodies, Monoclonal; D001779:Blood Coagulation Factors; D004768:Enterotoxins; D006684:HLA-DR Antigens; D007983:Lewis Blood Group Antigens; C026066:enterotoxin A, Staphylococcal; D013925:Thromboplastin