Abstract
Gelatinases (MMP-2 and MMP-9) play a key role during
invasion and metastazising of malignant cells and they have been
shown to be associated to invasive phenotype and poor prognosis in
several solid tumours. However little is known about their role in
hematological malignancies. In the present work, gelatinase
expression and its clinicopathological correlations were studied
with immunohistochemical staining in 10 cases representing normal
bone marrow aspirate smears, 123 cases representing diagnostic
bone marrow samples of patients with different leukaemias (35 AML,
7 CLL, 6 CML, 75 ALL), 67 diagnostic paraffin-embedded lymph node
biopsies from patients with Hodgkin's lymphoma and 57 biopsies
from patients with non-Hodgkin's lymphomas. The lymphoma samples
were also stained with factor VIII antibody to evaluate the extent
of new vessel formation and the non-Hodgkin's lymphoma cases also
with tissue inhibitor of metalloproteinases -1 (TIMP-1) antibody.
CLL did not express either of the MMP enzymes, while CML in the
chronic phase expressed strongly both of the enzymes. In ALL,
gelatinase expression was weak and detectable in pediatric cases
in only 12.7% and in the adults in 65% of the cases. In adult ALL,
MMP-2 expression correlated strongly with an extramedullary and
invasive pattern of disease presentation. In AML MMP-2 positivity
had markedly favorable prognostic and predictive power. In
lymphoma studies, no correlations could be detected between
gelatinase expression and the clinical parameters of invasion.
MMP-9 positivity was related to the presence of B symptoms, which
difference was statistically significant in Hodgkin's lymphoma. In
Hodgkin's lymphoma, strong MMP-9 expression also implicated
decreased neovascularization. In both lymphoma types, strong MMP-9
expression correlated with unfavorable prognosis, which difference
was statistically significant in non-Hodgkin's lymphomas and
remained as a tendency in Hodgkin's lymphoma. MMP-2 had
statistically significant association with a favorable prognosis
in Hodgkin's lymphoma. Combination of the results of both
stainings further increased prognostic power. All together these
findings implicate that gelatinases could be used as prognostic
tools in AML and lymphomas albeit this needs to be verified in
larger materials.
| Identifer | oai:union.ndltd.org:oulo.fi/oai:oulu.fi:isbn951-42-6942-X |
| Date | 14 February 2003 |
| Creators | Kuittinen, O. (Outi) |
| 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, 2003 |
| Relation | info:eu-repo/semantics/altIdentifier/pissn/0355-3221, info:eu-repo/semantics/altIdentifier/eissn/1796-2234 |
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