Abstract
Tumor invasion and metastasis are the major causes of treatment
failure or death for carcinoma patients. Matrix metalloproteinases
(MMPs) are zinc dependent endopeptidases implicated in tumor invasion
and metastasis. The expression of MMP-2 has been previously linked
to invasiveness of carcinoma cells. The MMP-2 immunoreactive protein
was studied here in squamous cell carcinoma of the utrine cervix
and in adenocarcinoma of the breast by using a specific monoclonal
antibody in immunohistochemical stainings. Immunoreactive protein
of latent MMP-2 was found to be an early event in neoplastic transformation
of the cervix in 60 patients. All cases of early stage cervical
carcinoma expressed the latent MMP-2 protein, suggesting that MMP-2
could be a prerequisite for invasive behavior. In early stage cervical
carcinoma the high score of MMP-2 expression seemed to be associated
with poor histological differentiation and lymph node metastases. The
intensitivity (score) of the immunoreaction was not, however, associated
with clinical behavior of this disease.
New predictive markers would be useful in selecting breast
carcinoma patients to different modalities of adjuvant therapy.
The MMP-2 protein has been found in breast carcinoma tumor cells
in immunohistochemical analyses. MMP-2 has been found to be expressed
in breast carcinoma in some preliminary studies, but there are no
reports so far that would show a correlation of MMP-2 to survival
in breast carcinoma. In the current study comprising 373 patients
the expression of MMP-2 protein was found immunohistochemically
in primary breast carcinomas. It is shown here for the first time
that immunoreactive protein of MMP-2 in primary breast carcinoma
is associated with a shortened relapse-free survival (RFS) or relative
overall survival (OS). MMP-2 correlated to the risk of failure during
the anti-estrogen adjuvant therapy in postmenopausal breast carcinoma
patients with axillary lymph node metastasis without a high tumor
burden. It was also found here that premenopausal patients with
a node positive breast carcinoma showing MMP-2 positivity relapsed
early after the primary operation. Young patients (< 40 years)
with MMP-2 positive tumors had a poor outcome when compared to other
node-positive premenopausal breast carcinoma patients. A patient
group with a high risk for an early relapse was identified from
node-positive, premenopausal breast carcinoma patients.
In conclusion, the present data show for the first time MMP-2
immunoreactive protein to be a prognostic factor in breast carcinoma,
indicating further studies to explore the value of this enzyme in
clinical decision making.
| Identifer | oai:union.ndltd.org:oulo.fi/oai:oulu.fi:isbn951-42-5402-3 |
| Date | 30 September 1999 |
| Creators | Talvensaari-Mattila, A. (Anne) |
| Publisher | University of Oulu |
| Source Sets | University of Oulu |
| Language | English |
| Detected Language | English |
| Type | info:eu-repo/semantics/doctoralThesis, info:eu-repo/semantics/publishedVersion |
| Format | application/pdf |
| Rights | info:eu-repo/semantics/openAccess, © University of Oulu, 1999 |
| Relation | info:eu-repo/semantics/altIdentifier/pissn/0355-3221, info:eu-repo/semantics/altIdentifier/eissn/1796-2234 |
Page generated in 0.0021 seconds