Plasminogen activator inhibitor-1 4G/5G polymorphism in breast cancer patients and its association with tissue PAI-1 levels and tumor severity.
BACKGROUND
The plasminogen activator inhibitor type 1 (PAI-1) 4G/5G polymorphism may have significance for PAI-1 expression. High levels of PAI-1 in breast cancer patients are associated with a poor prognosis. In this study, we analyzed the influence of the PAI-1 4G/5G polymorphism on tissue PAI-1 levels and its association with tumor severity in women with breast cancer.


METHODS
We studied 104 women with breast carcinoma (patient group) and 104 healthy age-matched women (control group). In patients and controls, the PAI-1 4G/5G polymorphism was determined by PCR amplification using allele-specific primers. In patients, PAI-1 levels were quantified in breast cancer tissue by using an ELISA.


RESULTS
The frequency of the PAI-1 4G allele tended to be higher in patients than in controls (p=0.062). The presence of the 4G allele (4G/5G plus 4G/4G genotypes) was significantly higher among patients with histological grade 3 tumors than among those with grade 1 tumors (p=0.026). Furthermore, patients with the 4G/4G genotype had significantly higher tissue PAI-1 levels than those with the 5G/5G genotype. Moreover, tissue PAI-1 antigen levels were significantly and positively correlated with tumor severity (p=0.003) and tumor size (p=0.009). However, no significant differences in PAI-1 level were observed in relation to menopause, hormone receptor or nodal status.


CONCLUSIONS
Tissue PAI-1 antigen levels and tumor severity seem to be associated with the PAI-1 4G/5G polymorphism. Further studies with a larger number of patients are needed to clarify the influence of this polymorphism in breast cancer.
Castelló
Remedios
R
Hospital Universitario La Fe, Centro de Investigación. Avda. Campanar 21, 46009 Valencia, Spain.
España
Francisco
F
Vázquez
Carlos
C
Fuster
Carlos
C
Almenar
Sergio M
SM
Aznar
Justo
J
Estellés
Amparo
A
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000483:Alleles; D001943:Breast Neoplasms / Q000235:genetics* / Q000378:metabolism; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D005838:Genotype; D006801:Humans; D008875:Middle Aged; D017395:Plasminogen Activator Inhibitor 1 / Q000235:genetics* / Q000378:metabolism; D011110:Polymorphism, Genetic; D011379:Prognosis; D020133:Reverse Transcriptase Polymerase Chain Reaction; D012720:Severity of Illness Index
D017395:Plasminogen Activator Inhibitor 1; C051321:SERPINE1 protein, human