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THE
PROGNOSTIC SIGNIFICANCE OF TYPE IV COLLAGEN AND MATRIX METALLOPROTEINASE-9
EXPRESSION IN COLORECTAL CANCER
Fenyvesi
A.
General
Hospital, Department of Pathology, Senta, Serbia and Montenegro
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ABSTRACT
Breakdown
of basement membrane is believed to be an essential step for tumor
invasion and metastasis. Matrix metalloproteinases family of endopeptideses,
degradative enzymes, is considered to play an important role in
tumor progression. Type IV collagen is a major structural protein
in the basement membrane and extracellular matrix, thus, much attention
has been focused on the type IV collagenases, (gelatinases, matrix
metalloproteinase-2 and matrix metalloproteinase-9), which specifically
degrade the basement membrane. On the other hand the interaction
between tumor cells and extracellular matrix can also result in
induction of basement membrane synthesis by tumor and stromal cells.
The aims of this study were to investigate distribution patterns
of type IV collagen expression at the basement membrane and matrix
metalloproteinase-9 expression in the tumor tissue of colorectal
carcinomas by immunohistochemical staining. The degree of production
of type IV collagen and matrix metalloproteinase-9 expression correlated
with classical clinicopathological prognostic factors and their
potential relationship with patients' prognosis. This study included
40 patients who underwent curative resection of colorectal cancer
at the Department of Surgery in the General Hospital Senta with
complete follow-up for 5 years or until death. The identification
of basement membrane and matrix metalloproteinase-9 expression were
performed immunohistochemically using monoclonal antibodies Collagen
IV (DAKO) and MMP-9 (Novocastra) at the invasive front of colorectal
cancer and were semiquantitatively assessed as mild, moderate or
severe. The deposition of basement membrane type of collagen IV
had statistically significant correlation with stage of disease
and histological grade of tumor with tendency of less synthesis
of basement membrane in the advanced stage of disease and poorer
histological grade of tumor. There were no significant correlations
between intratumoral basement membrane synthesis and sex and age
of patients, and localization and histological type of tumor. Five-year
survival rate in patients with mild synthesis of basement membrane
in colorectal tumor were significantly lower than in patients with
severe expression of basement membrane. There were no significant
correlations between intratumoral matrix metalloproteinase-9 expression
with major clinicopathological factors and with overall survival
of patients with colorectal carcinoma. By univariate Cox proportional
hazards model the basement membrane formation in colorectal cancer
was a prognostic factor with significance behind stage of disease
and histological grade of tumor, while expression of matrix metalloproteinase-9
did not show prognostic significance. Multivariate Cox analysis
verified that explicit synthesis of basement membrane showed a trend
toward better prognosis, but it was not statistically significant.
Immunohistochemical staining for type IV collagen is an important
additional staining technique with prognostic value.
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Keywords:
Colorectal neoplasms; Collagen; Basement membrane; Matrix metalloproteinase-9;
Prognosis |
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