MMP-2, MMP-9, VEGF and CA 15.3 in breast cancer.
BACKGROUND
Matrix metalloproteinases (MMPs) are a family of extracellular matrix degrading proteinases. Owing to their matrix-degrading abilities and high expression in advanced tumours, MMPs were originally implicated in cancer progression, invasion and metastasis.


METHODS
In this study, the correlation was determined between the expression of gelatinases (MMP-2 and MMP-9) in the sera of breast cancer patients from zymographic analysis and serum concentrations of VEGF and CA 15.3, before surgery and after 1 and 6 months; the association of both markers with clinicopathological features including histological type, stage of disease and estrogen (ER) and progesterone (PgR) receptors status were also analysed. In all, 88 breast cancer patients and 20 healthy women were involved in this study.


RESULTS
No statistically significant correlation between pro MMP-2, pro MMP-9, VEGF and CA 15.3 serum levels was found (p>0.05). In breast cancer patients, a significant decrease of the pro MMP-2 serum expression 1 month after surgery with respect to serum levels before surgery (p=0.0008) was evident, as well as of CA 15.3 serum levels at baseline and after 1 month (p=0.017). Moreover a strong decrease of pro MMP-9 serum levels was found in 88 breast cancer patients after 1 month (p=0.028) and after 6 months (p =0.009) from surgery. On the other hand, no significant differences in the serum levels of VEGF, CA 15.3, pro MMP-2 or pro MMP-9 between 88 breast cancer patients preoperatively and 20 healthy women as controls were found. Our findings did indicate a significant positive association between higher preoperative levels of CA 15.3 and progression of disease (p=0.03), as well as a longer disease-free survival in patients who exhibited a decrease of serum pro MMP-9 expression compared to other biomarkers. No relationship between these four markers and the main clinical and pathological parameters was found.


CONCLUSIONS
The present study failed to demonstrate any association between serum levels of MMPs, VEGF and CA 15.3 and well-known clinicopathological characteristics of breast carcinoma, while demonstrating the prognostic value of CA 15.3 and pro MMP-9 in the follow-up of breast cancer patients.
Quaranta
M
M
Department of Experimental Oncology, Laboratory of Analyses, Institute of Oncology, Bari, Italy. MicheleQuaranta@virgilio.it
Daniele
A
A
Coviello
M
M
Venneri
M T
MT
Abbate
I
I
Caringella
M E
ME
Di Tardo
S
S
Divella
R
R
Trerotoli
P
P
Di Gennaro
M
M
Schittulli
F
F
Fransvea
E
E
Giannelli
G
G
D014408:Biomarkers, Tumor / Q000378:metabolism; D001943:Breast Neoplasms / Q000201:enzymology*; D005260:Female; D006801:Humans; D020778:Matrix Metalloproteinase 2 / Q000378:metabolism*; D020780:Matrix Metalloproteinase 9 / Q000378:metabolism*; D008875:Middle Aged; D016019:Survival Analysis; D042461:Vascular Endothelial Growth Factor A / Q000378:metabolism*
D014408:Biomarkers, Tumor; C467484:VEGFA protein, human; D042461:Vascular Endothelial Growth Factor A; D020778:Matrix Metalloproteinase 2; D020780:Matrix Metalloproteinase 9