Shtabinskaya T.T., Bodnar
M.
Grodno State Medical
University, Belarus
PROGNOSTIC SIGNIFICANCE
OF MATRIX METALLOPROTEINASEs EXPRESSION
IN COLON ADENOCARCINOMA
WITH SYNCHRONOUS HEMATOGENIC METASTASES
The family of matrix
metalloproteinases (MMP) includes about 28 representatives of several classes
(collagenase, gelatinase and stromelysins), but only gelatinases (MMP-2 and
MMP-9) are capable of hydrolyzing the basic structural protein of the basal membrane
- type IV collagen - and participate in the invasive and metastatic potential
of tumors [1-3]. MMPs are involved in another mechanism of neoangiogenesis,
vascular mimicry, during which tumor cells are able to form communicating
channels between the islands of neoplastic cells [4]. These processes do not
exclude each other, moreover, in many cases are related to each other,
coexisting in both physiological and pathological neovascularization.
Purpose: to assess the
expression of matrix metalloproteinases in colon adenocarcinoma, depending on
the presence of synchronous hematogenous metastases and its significance for
predicting the course of the disease.
Materials and methods. Criteria for inclusion in the study: adenocarcinomas
of different degrees of differentiation. Exclusion criteria from the study:
primary-multiple cancers and neoplasms that have the histological structure of
the mucosa, micropapillary adenocarcinoma, kribroformnoy comedom carcinoma,
ring-cell, squamous and undifferentiated cancer.
The significance of MMP expression in colon
adenocarcinoma for the prognosis of the adjusted disease-free survival was
established by a prospective longitudinal study of 72 tumors verified and
removed in 29 men (40.3%) and 43 (59.7%) women. The age of patients ranged from
37.3 to 82.8 years. The median age at the time of surgery was 65.06
(60.42-72.86) years. The duration of follow-up was from 1 to 180 months.
The immunohistochemical study was performed using
mouse monoclonal antibodies to MMP-2 (NCL-MMP2-507, clone 17B11) and rabbit
polyclonal antibodies to MMP-9 (Dako A0150) by a standard procedure.
A quantitative evaluation of the expression level was
performed using the Aperio Image Scope program [5]. The total, parenchymal and
stromal positivity of MMP in the tumor was calculated.
Statistical analysis was performed using STATISTICA
10.0 (SNAXAR207F394425FA-Q). Due to the fact that the distribution of
quantitative parameters differed from normal (p <0.05), a comparative
analysis was conducted using nonparametric statistics methods.
Results. In 12 (16.7%) patients from the study group, hematogenous metastases
were found at the time of diagnosis. In 8 patients (11.1%) at the time of
detection of the disease, both lymphogenous and hematogenous were determined
(in the liver and lungs - 75% and 25%, respectively). Positivity levels of
MMP-2, MMP-9 were determined in the parenchymal and stromal components of the
tumor, as well as the overall level of positivity (Table 1).
Table 1. – MMPs expression depending on the
hematogenous spread
Positivity of expression |
Hematogenous spread |
р |
||
рМ0 |
рМ1 |
|||
MMP-2 |
Total |
0,042 (0,024-0,080) |
0,025 (0,018-0,059) |
0,184 |
Parenchymatous |
0,027 (0,006-0,052) |
0,012 (0,007-0,023) |
0,216 |
|
Stromal |
0,046 (0,019-0,087 |
0,031 (0,017-0,093) |
0,505 |
|
MMP-9 |
Total |
0,573 (0,373-0,651) |
0,517 (0,414-0,679) |
0,948 |
Parenchymatous |
0,679 (0,462-0,803) |
0,591 (0,520-0,836) |
0,896 |
|
Stromal |
0,381 (0,258-0,483) |
0,422 (0,182-0,542) |
0,986 |
As can be seen from Table 1, the expression area of
matrix metalloproteinases was higher in adenocarcinoma without synchronous
metastases, but these differences were insignificant (p> 0.05). Also, there
were no significant differences in the expression of the studied marker of
angiogenesis, depending on the appearance of new metastases (p> 0.05).
The construction of a multifactor model for predicting
the 5-year outcome depending on hematogenous distribution and the expression of
MMPs was carried out using Cox regression by a direct step-by-step method. The
grouping sign was the outcome of cancer at 5 years from the moment of surgery,
as assessed by the adjusted disease-free survival. It has been established that
only lymphogenous and hematogenous metastasis significantly affects the
five-year survival rate.
The values of the likelihood function, the statistical criteria
of the model for each of the regression steps, the numerical values of the coefficients of independent variables and their
characteristics are described in the previous article [6].
Conclusion. The levels of MMPs expression can not be used as an
independent prognostic factor.
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Shtabinskaya, M. Bodnar // Научният потенциал на света – 2017: материали XIII Междунар. науч.-практ. конф., София,
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