Abstract
We examined the expression level of several genes that regulate distinct steps of metastasis in 55 formalin-fixed, paraffin-embedded, archival specimens of primary human ovarian carcinoma from patients undergoing curative surgery. The expression of vascular endothelial growth factor/vascular permeability factor (VEGF/VPF), basic fibroblast growth factor (bFGF), E-cadherin, type IV collagenase, matrix metalloproteinase (MMP-2 and MMP-9), and interleukin 8 (IL-8) was examined by a colorimetric in situ mRNA hybridization technique. The expression level of E-cadherin, MMP-2, MMP-9, VEGF, and IL-8 mRNA correlated with disease stages. The ratio of type IV collagenase expression (mean of the expression of MMP-2 and MMP-9) to E-cadherin expression (MMP:E-cadherin ratio) increased with increasing stage of disease (p<0.0001). Death rates significantly increased with high MMP:E-cadherin ratio (p=0.0005). Multivariate analysis of overall survival showed that the MMP:E-cadherin ratio was a significant independent prognostic factor, even after adjustment for known prognostic factors, such as histology, stage, and age.
Publication types
-
Research Support, U.S. Gov't, P.H.S.
MeSH terms
-
Adult
-
Aged
-
Aged, 80 and over
-
Biomarkers, Tumor / genetics*
-
Biomarkers, Tumor / metabolism
-
Cadherins / genetics
-
Cadherins / metabolism
-
DNA Primers / chemistry
-
Disease Progression
-
Endothelial Growth Factors / genetics
-
Endothelial Growth Factors / metabolism
-
Female
-
Fibroblast Growth Factor 2 / genetics
-
Fibroblast Growth Factor 2 / metabolism
-
Gene Expression
-
Humans
-
In Situ Hybridization
-
Interleukin-8 / genetics
-
Interleukin-8 / metabolism
-
Lymphokines / genetics
-
Lymphokines / metabolism
-
Matrix Metalloproteinase 2 / genetics
-
Matrix Metalloproteinase 2 / metabolism
-
Matrix Metalloproteinase 9 / genetics
-
Matrix Metalloproteinase 9 / metabolism
-
Middle Aged
-
Neoplasm Proteins / genetics*
-
Neoplasm Proteins / metabolism
-
Neoplasms, Glandular and Epithelial / genetics
-
Neoplasms, Glandular and Epithelial / metabolism*
-
Ovarian Neoplasms / genetics
-
Ovarian Neoplasms / metabolism*
-
RNA, Messenger / metabolism
-
Vascular Endothelial Growth Factor A
-
Vascular Endothelial Growth Factors
Substances
-
Biomarkers, Tumor
-
Cadherins
-
DNA Primers
-
Endothelial Growth Factors
-
Interleukin-8
-
Lymphokines
-
Neoplasm Proteins
-
RNA, Messenger
-
Vascular Endothelial Growth Factor A
-
Vascular Endothelial Growth Factors
-
Fibroblast Growth Factor 2
-
Matrix Metalloproteinase 2
-
Matrix Metalloproteinase 9